Science Education in a Rapidly Changing World [1 ed.] 9781617610387, 9781617289149

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Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

EDUCATION IN A COMPETITIVE AND GLOBALIZING WORLD

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

SCIENCE EDUCATION IN A RAPIDLY CHANGING WORLD

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Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

EDUCATION IN A COMPETITIVE AND GLOBALIZING WORLD

SCIENCE EDUCATION IN A RAPIDLY CHANGING WORLD

SETH D. GRAHAME

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

EDITOR

Nova Science Publishers, Inc. New York

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers‘ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works.

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Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA

Science education in a rapidly changing world / Seth D. Grahame. p. cm. Includes bibliographical references and index. ISBN HERRN 1. Science--Study and teaching. I. Grahame, Seth D. Q181.S36886 2010 507.1--dc22 2010025947

Published by Nova Science Publishers, Inc. † New York

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

CONTENTS Preface Chapter 1

Chapter 2

Chapter 3 Chapter 4

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Chapter 5 Chapter 6

Chapter 7

Chapter 8

Chapter 9

Chapter 10

vii Recollections of 45 Years in Research: From Protein Chemistry to Polymeric Drugs to the EPR Effect in Cancer Therapy Hiroshi Maeda Educational Changes in Preventing Infection Risk Due to Occupational Blood-Borne Exposure Emanuele Amodio, Nino Romano and Maria Antonella Di Benedetto Learning and Teaching of Computer Programming: Past and Future Wilfred W.F. Lau and Allan H.K. Yuen Providing Scenario-Based, Multi-Disciplinary, Disaster Education: The Successive Approximation Approach Kelly Burkholder-Allen,Paul Rega, Christopher Bork and Churton Budd A Psychological Perspective on Media Literacy M. M Terras, Ramsay and E. Boyle Investigation of New Education Methods Using Applied Mechatronics Sezgin Ersoy Putting Beliefs About Nature of Science into Practice: Prospectıve Elementary Scıence Teachers‘ Case Definitions and Significance of Epistemological Beliefs and Belief About the Nature of Science in Relation with Scientific Literacy Esra Macaroglu Akgul Science Education through Research Katsuhito Kino, Takanobu Kobayashi, Rie Komori, and Hiroshi Miyazawa Science and Technology Museums as Places for Critical Thinking Skill Development Kristin Knipfer and Daniel Wessel Quality Managment for Science Education Teodora Ruginosu and Sezgin Ersoy

Index

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

1

31

47

61

75

87

101 125

137 145 151

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved. Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

Copyright © 2011. Nova Science Publishers, Incorporated. All rights reserved.

PREFACE This book explores the broad spectrum of science education in a rapidly changing world with a focus on such topics as mechatronics, a multidisciplinary field combining mechanical engineering, electronics and computer technology; science education through research, science and technology museums as places for critical thinking. Chapter 1 - This article describes the lifelong research experience of a scientist, from the beginning studies of protein chemistry to development of a protein drug (neocarzinostatin, NCS) to the invention of the first polymer conjugate drug—poly(styrene-co-maleic acid (SMA) conjugated to NCS, －called SMANCS. The author, having acquired knowledge of proteases and inhibitors, pioneered investigations of microbial proteases in the pathogenesis of bacterial infection. The author‘s group, using a polymer-conjugated enzyme (superoxide dismutase), discovered an enormous burst in the generation of superoxide anion radical (O2・－) during influenza virus infection by the generation of xanthine oxidase. O2・－ was found to be the major cause of the pathogenesis of this viral infection, which progressed even after the virus was eradiated. These events can be interpreted as advancing beyond the boundary of Robert Koch‘s postulates, that is, viral disease occurring in the absence of virus. Also, the importance of endogenous free radicals, now referred to as reactive oxygen species (ROS) and reactive nitrogen species (RNS), during the microbial infections. Role of ROS and RNS in human disease and health became clear, in that they were crucial factors for development of (eg. drug-resistant mutant) formation of mutant microorganisms in chronic and acute infections as well ass carcinogenesis. In additional studies of the pathogenesis of infections of bacterial and fungi, activation of the kallikrein-kinin cascade and thus bradykinin generation at the site of infection were found to result in pain and enhancement of vascular permeability (edema). Because no potent inhibitors of bacterial proteases exist in the human body, such proteolytic activity is detrimental to the host. The intense enhancement of vascular permeability of bacterial infection or inflammation was later found to be analogous to the situation in cancer tissues. That finding led to the discovery of the EPR (enhanced permeability and retention) effect of macromolecules (>40 kDa) in solid tumors. This EPR effect can be utilized for targeting of macromolecular anticancer drugs to tumors, in the field that is today known as nanomedicine. The EPR effect is now becoming a universal guiding principle for tumor selective targeting in nanomedicine for design of drugs such as polymer conjugates, liposomes, micelles, antibodies, and DNA/carrier complexes etc. The polymer conjugate drug SMANCS made remarkable pinpoint targeting possible with unprecedented selectivity: i.e., a

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viii

Seth D. Grahame

tumor/blood ratio of >2000 was achieved. Further enhancement, 2- to 3-fold, of the EPR effect, and thereby more tumor selective drug delivery became possible via either angiotensin II-induced elevation of blood pressure or application of nitroglycerin ointment (which produces nitric oxide in tumors). As described in the text, such interactions of multiple disciplines and of basic science and clinical problems have yielded many discoveries that will be invaluable to young scientists and future directions and development in the medical sciences. Chapter 2 - With the emergence of AIDS in the early 1980s, concerns about the transmission of blood-borne pathogens began to grow in the workplace including in the healthcare setting. Responding to these concerns, the Centers for Disease Control and Prevention (CDC) in the USA have issued Universal Precautions [1], followedby Standard Precautions [2], aiming to protect healthcare workers (HCWs) from exposure to blood-borne pathogens. Standard Precautions combine the major features of Universal Precautions and Body Substance Isolation [3] and are based on the principle that blood, body fluids, secretions, excretions except sweat, non-intact skin, and mucous membranes may contain transmissible infectious agents. Chapter 3 - Research into computer science education has spanned a broad range of topics. Learning to program is notably an area that has received much attention over the years since virtually every computer science program requires the mastery of programming skills and knowledge. This chapter aims to review four significant research strands of learning and teaching of computer programming, namely cognitive consequences and transfer effects of learning of computer programming, differences between novices and experts, programming knowledge and strategies, and program comprehension and composition. It first surveys some important studies performed in these strands in the past. Then for each strand, it recommends some literature-based research directions for future studies. While these recommendations still need further empirical support, such a review provides valuable avenues for researchers and practitioners alike towards advancement in their professions. Chapter 4 - The traditional approach to disaster education lacks depth. Curricula are often comprised of a collection of the ―hazard du jour‖ and presented in the traditional didactic lecture format to an audience of individuals from a single discipline. While the key concepts presented may provide sufficient knowledge for successful completion, there is ample research to demonstrate that the preponderance of professionals who successfully complete these traditional, lecture-style programs consider themselves ill-prepared to respond to incidents [1]. Additionally, recent reports indicate that healthcare providers, hospitals, health systems, cities, states, and the country as a whole scored poorly in preparedness for a catastrophic health event [2-5]. These shortcomings may be related to the learning environment and didactic approach in which most disaster education is conducted. A learning environment that is static, one dimensional, non-interactive, and introduces content in black and white only, does not reflect the spontaneous, dynamic, and multidimensional incidents that our responders are called upon to manage in living color. The authors find this practice to be unacceptable and offer an alternative approach. Although the traditional approach to disaster education may enhance the adult learners‘ knowledge-base on a given hazard, it often lacks the ability to enhance critical decisionmaking and other skills that improve their ability to effectively manage an incident. Management of emergencies and disasters takes place on multidisciplinary, multiagency, multijurisdictional levels and is predicated on a systematic approach which manages by

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Preface

ix

objectives. The five-step process used in this management approach includes establishing incident objectives, developing strategies based on the overarching incident objectives, developing assignments, plans, and procedures, establishing measurable tactics for functional activities, while providing direction to attain those tactics, and documentation of results in order to measure performance and to facilitate corrective action. A multidisciplinary, systematic, and proactive approach is the foundation of National Incident Management System (NIMS) [6], which provides guidance to jurisdictions so that they may work together in a seamless manner to protect against, respond to, recover from, and mitigate the effects of incidents. NIMS integrates the best practices into a comprehensive framework and provides a template for incident management for emergency management and response personnel in the context of all-hazards, working in conjunction with the National Response Framework (NRF) [7] National Incident Management System]. The ―systems approach‖ is also supported by the National Health Security Strategy (NHSS), recognizing that many interrelated systems are critical to support health at the individual and community levels and to protect them and support their recovery from an incident [8]. Overall, the strategic objectives of the NHHS support the significance and relevance of scenario-based training by highlighting the importance of fostering informed and empowered individuals and communities; developing and maintaining a well-trained workforce, ensuring situational awareness; fostering integrated, scalable healthcare delivery systems; ensuring timely and effective communications; promoting effective countermeasures enterprises; ensuring prevention/mitigation of environmental and emerging health threats;incorporating post-incident recovery into planning and response;working with partners across the border and around the globe; and finally, by ensuring that all systems which support the security of our Nation‘s health are grounded in science, evaluation, and quality improvement methods. It is essential that emergency management /response personnel possess the requisite knowledge, skills, and abilities to optimize personal performance and contribute to the overall successful management of disasters. Emergency responders is a broadly defined category and collectively includes individuals from Federal, State, territorial, tribal, regional, and local governments, non-governmental organizations (NGO‘s), private sector organizations and industries, critical infrastructure/key resource owners and their operators, and individuals from any organization, or persons who assume any role in emergency management [NIMS]. The quality and overall effectiveness of disaster education and training provided for emergency responders would be greatly enhanced if the delivery transitioned beyond the current traditional didactic approach to a more dynamic, multidisciplinary, and multidimensional approach. It is believed that this vision can be realized by offering scenariobased education that engages learners as active, rather than passive, participants in the process of enhancing their knowledge, skills, and abilities as a responder. This chapter explores the concept of scenario-based education using the ―Successive Approximation‖ approach for providing disaster-related education to our Nation‘s current and future responders. Chapter 5 - In today‘s technology-driven society, the ability to effectively use information and communication technology (ICT) is essential in an educational context. The ability to ―access, understand and create communications in a variety of contexts‖ (Ofcom, 2009, pg 4) is known in the UK as Media Literacy. To date, research on media literacy has focused primarily on the impact of demographic factors such as age, gender and socio-economic status. Apart from personality factors, the key role that Psychological factors play in media literacy has been overlooked. When viewed through a Psychological lens it is clear that all

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three components of media literacy: access, understanding and creation require in-depth examination both separately and in combination. This analysis applies at both the theoretical level and the empirical level. The authors ask: how Psychologically valid are current conceptions of media literacy? How accurately do they reflect perceptions and experiences of media use? The authors propose that the consideration of the psychological dimensions of media literacy skills is crucial if the authors are develop and full understanding of media literacy skills and capitalise on the learning potential of Web 2 technology. In this paper the authors highlight how Psychological theory and research has previously contributed to our understanding of our interactions with technology, the process of learning and consider how psychology can contribute to our understanding and application of new technologies within education. As a discipline with the objective of understanding behaviour, the consideration of the Psychological dimensions of Media Literacy is crucial for both education and society. Chapter 6 - Mechatronics is an area that merges multidisciplinary knowledge coming from mechanical engineering, electronics and computer technology. Vocational training in mechatronics requires the teaching of ―multi-skills‖ and ―multi-intelligent‖ in various learning contexts, as well as a good blend of learning in the classroom and practical training in schools where is steered with quality management system. Quality education is the education in which the provider offers education services in accordance with certain standards, develops skills, attitudes that enable a person to accede to a higher stage of career development, self discovery, personality development, adaptability to labor market and life long learning. Quality in education must be defined not only on the basis of what is needed now for an adult or a young person but depending on how it manages to meet future needs. A quality education is not only to ensure progress in achieving predetermined objectives, but also to set new trends and new ways of achieving them. Vocational training colleges together with industry are confronted with the need to develop and integrate theoretical and practical learning sequences that are able to fulfill the demands for multi-skilled technicians and skilled workers. The claim for work-related learning based on the interleaving of theoretical learning and learning by practical work and experimentation is obvious [1] A major goal in mechatronics training is that students have to acquire theoretical and operational knowledge and practical competencies in terms of technical core skills. This type of skills generally relates to the assembly and service of complex machines, plants and systems, in the field of plant construction and mechanical engineering, and in those companies that purchase and operate such mechatronic systems. It describes the effect of some learning methods that apply quality management in an organized educational environment and system. Mechatronics is an interdisciplinary science, so the authors have to use different learning methods according to the curricula‘s specific target. The main aim of this paper is to increase the learning levels of mechatronics education in order to have and efficient assessment [2]. Chapter 7 – Knowing what science is, how scientific knowledge is produced, what limitations does this knowledge has, who is a scientist and how does scientist work, in other words, understanding the nature of science corresponds to individuals‘ scientific literacy (Macaroglu, 1999). World-wide research shows that many people are not well informed about science. Therefore; scientific literacy is one of the emphases cited in science education programs throughout the world. The major limitations in scientific literacy can be attributed to many factors. One of the important factors cited in the literature is the knowledge of

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science and science teaching pedagogy of elementary school teachers. Therefore, there is a need to study elementary school teachers‘ knowledge of science and science teaching pedagogy. Chapter 8 - The present world is rapidly changing at all times. Students must try hard to adjust themselves to such a world. Here, the authors showed our previous researches (I the mechanism of point mutations, ii the drug discovery using in silico, iii the study of mouse DNA polymerase alpha, iv the genetic analysis of biogenetical times) and described the knowledge, the skills and the logic of chemistry and biology required for these researches. Logical thinking and the capability to respond to diverse situations were needed for success. As research is conducted by making full use of a wide range of the researcher‘s ability, students will be able to acquire the capabilities, such as logical thinking and adaptability, through experiences of the research studies. Thus, the education acquired through research will help students to adapt to the rapidly changing world. Chapter 9 - Based on our experience in the field of psychological research in museums, with the two focal points of supporting critical thinking and the potentials of mobile devices, the authors argue that critical thinking – a crucial skill in our rapidly changing world – can and should be supported in informal settings such as science museums by means of mobile devices: As our world is rapidly changing, the lay public is required to inform themselves about contemporary socio-scientific issues constantly throughout life to make deliberative decisions as participants of our democratic knowledge society. For reflective judgment, critical thinking skills are essential. However, respective abilities and dispositions are often lacking, and therefore developing critical thinking skills is one of the desired outcomes of modern science education. The authors argue that science museums are an excellent setting for skill development: They present sufficient information serving as a basis for reflective judgment and critical thinking if visitors are supported in activities such as the evaluation of opposing arguments and integration of controversial information. This support can easily be accomplished by tapping into the potential of visitors‘ personal mobile devices. By offering tools that facilitate the fundamental cognitive processes of critical thinking, visitors‘ reflective judgment is supported during their visit. If the tools are available on the visitors‘ personal devices (e.g., cellphones), they could access the tool again at any time in their daily life. As an illustration for this argument, the authors present a design draft of such a tool, which is based on current psychological knowledge about critical thinking and reflective judgment, and the authors outline its specific potential for critical thinking skill development in informal settings. Silver nanoparticles could be key to devices that keep hearts beating strong. New fibre nanogenerators could lead to electric clothes. 'Fertility chip' to accurately count spermatozoa in sperm. Report highlights nanotech retreat. Stem cell capsules may help mend broken bones. EPA SAP releases report on nanosilver and other nanometal pesticide products. Dangerous Nanoparticles Can be Transported by Insects Chapter 10 - Quality of services offered by an educational institution represents all the features of a study program and its provider, through which the beneficiary‘s expectations are met, as well as the quality standards.

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In: Science Education in a Rapidly Changing World Editor: Seth D. Grahame

ISBN 978-1-61728-914-9 © 2011 Nova Science Publishers, Inc.

Chapter 1

RECOLLECTIONS OF 45 YEARS IN RESEARCH: FROM PROTEIN CHEMISTRY TO POLYMERIC DRUGS TO THE EPR EFFECT IN CANCER THERAPY Hiroshi Maeda* Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, and Division of Applied Chemistry, Graduate School of Engineering, Sojo University, Kumamoto, 860-0082 Japan

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ABSTRACT This article describes the lifelong research experience of a scientist, from the beginning studies of protein chemistry to development of a protein drug (neocarzinostatin, NCS) to the invention of the first polymer conjugate drug— poly(styrene-co-maleic acid (SMA) conjugated to NCS, －called SMANCS. The author, having acquired knowledge of proteases and inhibitors, pioneered investigations of microbial proteases in the pathogenesis of bacterial infection. The author‘s group, using a polymer-conjugated enzyme (superoxide dismutase), discovered an enormous burst in the generation of superoxide anion radical (O2・－) during influenza virus infection by the generation of xanthine oxidase. O2・－ was found to be the major cause of the pathogenesis of this viral infection, which progressed even after the virus was eradiated. These events can be interpreted as advancing beyond the boundary of Robert Koch‘s postulates, that is, viral disease occurring in the absence of virus. Also, the importance of endogenous free radicals, now referred to as reactive oxygen species (ROS) and reactive nitrogen species (RNS), during the microbial infections. Role of ROS and RNS in human disease and health became clear, in that they were crucial factors for development of (eg. drug-resistant mutant) formation of mutant microorganisms in chronic and acute infections as well ass carcinogenesis.

* Corresponding author. Tel.: +81 96-326-4114; fax: +81 96-326-4114. E-mail address: [email protected].

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Hiroshi Maeda In additional studies of the pathogenesis of infections of bacterial and fungi, activation of the kallikrein-kinin cascade and thus bradykinin generation at the site of infection were found to result in pain and enhancement of vascular permeability (edema). Because no potent inhibitors of bacterial proteases exist in the human body, such proteolytic activity is detrimental to the host. The intense enhancement of vascular permeability of bacterial infection or inflammation was later found to be analogous to the situation in cancer tissues. That finding led to the discovery of the EPR (enhanced permeability and retention) effect of macromolecules (>40 kDa) in solid tumors. This EPR effect can be utilized for targeting of macromolecular anticancer drugs to tumors, in the field that is today known as nanomedicine. The EPR effect is now becoming a universal guiding principle for tumor selective targeting in nanomedicine for design of drugs such as polymer conjugates, liposomes, micelles, antibodies, and DNA/carrier complexes etc. The polymer conjugate drug SMANCS made remarkable pinpoint targeting possible with unprecedented selectivity: i.e., a tumor/blood ratio of >2000 was achieved. Further enhancement, 2- to 3-fold, of the EPR effect, and thereby more tumor selective drug delivery became possible via either angiotensin II-induced elevation of blood pressure or application of nitroglycerin ointment (which produces nitric oxide in tumors). As described in the text, such interactions of multiple disciplines and of basic science and clinical problems have yielded many discoveries that will be invaluable to young scientists and future directions and development in the medical sciences.

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1. BON VOYAGE: PASSAGE TO THE MACROMOLECULAR WORLD AND PROTEIN CHEMISTRY After obtaining my BS degree from Tohoku University, in Sendai, Japan, in March, 1962, I applied for an extremely competitive Fulbright Graduate Study Fellowship to study in the United States. With great luck, I was accepted into the Fulbright program for study at the University of California, Davis, for 2 years. There, I met Professor Robert E. Feeney, in August, 1962, for the first time; he was to become my mentor throughout my academic career. Professor Feeney, who passed away in September, 2007, was well known for his research on egg white proteins and, more specifically, on ovomucoids and other protease inhibitors. He may be better known, however, for his research on antifreeze glycoprotein found in blood plasma of Arctic and Antarctic fishes. He is also famous in the field of chemical modification of proteins. These research areas in fact became the basis of my own future research directions and developments. At the University of California, Davis, my MS thesis concerned the molecular microheterogeneity of primarily the egg white protease inhibitors called ovomucoids with genetically identical backgrounds. The remarkable progress in protein chemistry and biochemistry during those days is comparable to that of genomic science at the end of the 20th century. My curiosity about the life sciences led me to choose medical science as my future interest.

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Recollections of 45 Years in Research: From Protein…

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2. BACK TO SENDAI AND THE WORLD OF ANTIBIOTICS After finishing my MS degree at Professor Feeney‘s laboratory, I returned to Sendai, Japan, which is about 350 km north of Tokyo, where I continued my studies at Tohoku University Medical School in Professor Nakao Ishida‘s Department of Bacteriology. When I had been an undergraduate, in 1960, I had the microbiology class that was taught by Dr. Ishida, who was then an associate professor at Tohoku University Medical School. He later became known throughout the world as the virologist who discovered Sendai virus, who passed a way in December 2009 during preparation of this manuscript. In Sendai, my first research project under Professor Ishida‘s supervision was to isolate interferon from the allantoic fluid of virus-infected embryonated chicken eggs. At that time, interferon was vaguely known as a protein, but not much more was known. World-class research projects, particularly studies of virus, were conducted in that department, but a program that screened for bioactive compounds with antibacterial, antiviral, or antitumor activity was also actively pursued. By means of this screening program, Ishida‘s group discovered a unique antitumor protein, with unprecedented activity, which was named neocarzinostatin (NCS). Because of my former experience in protein chemistry, Professor Ishida assigned me to the investigation of the biochemical and chemical nature of NCS (1). The biological activity of NCS were studied primarily by Katsuo Kumagai, MD, who had originally been a clinician but then a junior faculty member and later became Professor of Microbiology at Tohoku University School of Dentistry. The Southern Research Institute of the National Cancer Institute in the United States also evaluated the antitumor activity of NCS in the murine Walker 256 tumor model and showed NCS to be one of the most active compounds evaluated among 50 or so new candidate drugs at that time. To clarify the chemical structure of NCS, we initiated amino acid sequencing of NCS. Use of Sanger‘s reagent, dinitrofluorobenzene, that is coupled to N-terminal amino acid (to obtain dinitrophenylated derivatives), and Edman‘s degradation using phenylisothiocyanate was routine proceadures. The automatic amino acid analyzer was also becoming a common tool in protein chemistry. In addition, dansyl derivatization with a resultant higher fluorescence sensitivity, together with thin-layer chromatography, became an accepted method for detection of N-terminal amino acid residues. Despite of inadequate resources, we began the research on amino acid sequencing of NCS. Meantime we developed a highly sensitive amino acid sequencing methos using fluorescein isothiocyanate (FITC), similar to the Edman reagent but much higher sensitirity, for which Hiroshi Kawauchi, a graduate student (a few year junior to me, who later became Professor of Kitazato University and one of the most expert of the pituitary hormone of fish ) contributed a lots, first by synthesizing pure FITC; commercial FITC at that time had a purity of no better than 60%, far from good chemistry. Although we published few papers, the method did not become popular because no effort for commercialization was made in one reason (2-4). Any innovative project or large research undertakings required substantial funding. To obtain such research money, we applied to the National Institutes of Health (NIH) of the United States. Several months after submission of the application to the NIH, we received a letter that our application was successful. However, our excitement was temporary. A few weeks after that letter, we received another letter from the Office of General Accounting

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Hiroshi Maeda

stating that the grant could not be funded, perhaps because of the Vietnam War. Student sentiments against the Vietnam War were so strong that they would target the United Statessupported research project, even though academic, with violence.

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3. ON TO THE UNITED STATES: WORK AT CHILREN’S RESEARCH FOUNDATION AND HARVARD MEDICAL SCHOOL Within a few months, Professor Ishida received a letter from Professor Sidney Farber, MD (1903–1973), who was the founder and Director of Children‘s Cancer Research Foundation (CCRF) of Children‘s Hospital Boston, at Harvard University Medical School; (CCRF is now Dana-Farber Cancer Institute). The letter stated that he and Dr. Meienhofer‘s group were interested in NCS and wanted to collaborate in research on NCS. The letter was accompanied by a letter from the late Johannes Meienhofer, PhD, at the same institute, who would be in charge of the project. Such an offer from Harvard was quite appealing, and Dr. Ishida decided that I should go to Boston next year, after my PhD degree was conferred. Dr. Farber was a pathologist and pediatric oncologist who was well known throughout the world, as Professor at Harvard Medical School, and President of the American Cancer Society (1968–1969). He believed strongly that cancer chemotherapy would be effective, and he developed the concept of total care of pediatric cancer patients, which meant primarily free care and a wide range of support services at CCRF. He pioneered treatments of Wilms‘ tumor (a kidney cancer) of children with actinomycin D and of lymphoma and leukemia with methotrexate. Dr. Meienhofer was a synthetic peptide chemist working at CCRF, who had been trained in Aachen, Germany, and was involved in the organic synthesis of insulin under Dr. Helmut Zahn. After I arrived in Boston in May, 1968, I started work on the amino acid sequencing of NCS by using the dansyl-Edman method. To gain more experience in amino acid sequencing, I was sent to the Hormone Research Laboratory of the University of California, San Francisco (UCSF), where Professor Chao Hao Li (1913–1987), who was a friend of Dr. Farber and a scientific consultant to CCRF, was the director. I spent about 2 weeks at the UCSF Hormone Research Laboratory near Golden Gate Park in San Francisco. What I found was an unusual characteristic of NCS: it resisted chemical reduction of its two disulfide bonds, even under the excess amount of reducing agents, 5 M guanidine-HCl or 8 M urea. To reduce and alkylate NCS, I developed a new method of disulfide bond reduction in liquid ammonia with dithiothreitol, which worked perfectly; this method was published in 1971 in the Journal of the American Chemical Society (5). The remainder of my work involved peptide fragmentation with trypsin, chymotrypsin, and thermolysin, and manual Edman degradation. At that time, high-pressure liquid chromatography for separating peptide fragments was not available, amino acid analysis was not completely automated, and 6 N HCl hydrolysis at 110 C in vacuo was, of course, required. Tedious labor-intensive efforts were thus prerequisites for amino acid sequencing. About 1 year later, when the project was under way and productive, a postdoctoral fellow, Charles Glaser, joined in our group. When the major portion of the work was almost completed, Dr. Glaser went to UCSF for a second postdoctoral fellowship, and Kenji Kuromizu, another postdoctoral fellow from Kyushu University, Japan, joined our laboratory to help with this project. The total amino acid

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sequence was completed before long after his arrival (6-8). The positions of the two disulfide bridges in NCS were determined later, after we returned to Japan (9), and a minor revision of the amino acid sequence (10) was also determined primarily by Dr. Kuromizu. In the early summer of 1971, I received a letter from Professor Yorio Hinuma, MD, asking me to accept the associate professorship position at his Department of Microbiology at Kumamoto University Medical School. Dr. Hinuma became world known by his discovery of the human T-cell leukemia virus in later year, which is the causative agent of adult T-cell leukemia, for which he received the Hammer Award, among others. He also received the Order of Culture from the Emperor of Japan in 2009. His offer was a challenge for me, inasmuch as the amino acid sequence of NCS was almost completed, so I accepted the offer. I returned to Sendai in the middle of September, to finish work in my previous position, and then in October I moved to Kumamoto to begin work at my new position.

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4. KUMAMOTO UNIVERSITY IN KYUSHU, JAPAN I had no acquaintances or relatives in Kumamoto, which is located in the central region of Kyushu Island. Kumamoto University Medical School is an old school with a long history that can be traced back to the 18th century. I continued my studies of NCS, such as chemical modification and structure-activity relationships, biochemical and molecular mechanisms of action, tissue distribution, and pharmacokinetics, pharmacodynamics, and degradation in vivo. One very interesting finding was the highly lymphotropic nature of NCS after subcutaneous injection. When 14C-labeled succinylated NCS was injected subcutaneously, it accumulated primarily in regional lymph nodes (11). Lymphatic tissue is known to be the preferred site of cancer metastasis, which is why lymphatic metastasis occurs so frequently. This lymphotropic drug accumulation motivated me to devise a strategy for treatment of lymphatic metastasis by utilizing this property: that is, delivering the drug directly to the lymphatic system. In fact, in lymphology, macromolecules and lipids were well known to be preferentially recovered by the lymphatic system after injection into the interstitial space. In other words, lipophilic and macromolecular derivatization of NCS would likely make such lymphotropic drug delivery possible, which would be ideal for an anti-lymphatic metastasis strategy. We also showed that, at a subcellular level, intracellular uptake was needed for DNA degradation by NCS. This finding meant that NCS activity occurred inside cells after entry by endocytosis, rather than signal modulation leading to NCS activity at the surface of the cell membrane (12-14). Succinylation of NCS suggested that two of the free amino groups in NCS (one at the N-terminal alanine 1 and the other at lysine 20) could be utilized for modification without loss of activity (15,16). During this work, I found an advertisement in Chemical and Engineering News stating that poly(styrene-co-maleic anhydride) (SMA) could be used as car wax and floor polishing materials, which were water and solvent-soluble, hydrophobic polymers containing maleic anhydride. As was a case of succimic anhydride it would react with amino groups of NCS. Thus, I planned to modify two amino groups of NCS with SMA polymer. I expected that attachment of SMA to NCS would confer a potential (perhaps ideal) lymphotropic property to NCS. For this purpose, I asked ARCO in Philadelphia for a small sample of SMA, and they generously sent me several 1-lb bottles of SMA with different specifications.

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Without much difficulty, I reacted SMA (with a relative molecular mass Mr about 5 kDa) and NCS in bicarbonate buffer (pH 8.5), and purified and verified that two SMA chains were conjugated to NCS, which I named SMANCS (Figure 1). The first paper on the synthesis of SMANCS appeared in the International Journal of Peptide and Protein Research in 1979 (17). Descriptions of the biological and pharmacological properties of SMANCS, including its highly lymphotropic nature, were subsequently published (18-20).

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S MA

Prot ein

Figure 1. Chemical structure of SMANCS. SMANCS consists of three components: two chains of styrene-co-maleic acid polymer, a protein portion, and the chromophore of NCS.

Because industrial-grade SMA was unfit for pharmaceutical development, I collaborated with the Kuraray Company in Kurashiki, Japan, which had experts in polymer chemistry and was highly interested in developing pharmaceuticals. After we compared various alkyl side chains of half-alkyl esters of maleic acid residues, we chose to work with the n-butyl halfester of SMA for a number of reasons. The details of this synthesis and the chemistry of SMANCS were published in the Journal of Medicinal Chemistry in 1985 (21). With the fully characterized polymer-conjugated antitumor protein SMANCS in hand, my graduate student Jiro Takeshita (who later became an anesthesiologist) and I were on board for a big voyage on the ocean of macromolecular pharmacology, or polymer therapeutics, as Professor Ruth Duncan later preferred to call it. In the late 1960s, the clinical development of NCS had started a phase I/II study in Japan, although anecdotal accounts had previously confirmed its efficacy (22,23). In this regard, my old close friend since college freshman in Tohoku University Medical School, Dr. Kanamaru, who later became a professor of clinical oncology, was the first doctor to apply NCS in human that is now considered phase 0/I. Professor Nakao Ishida, who was the director of the project, collaborated with Kayaku Antibiotic Laboratory of Tokyo on the manufacturing of NCS and later with Yamanouchi Pharmaceutical Company (now Astellas) for marketing.

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After my return to Japan in 1971, I became a member of the NCS project and was often asked to give lectures on the chemistry, biochemistry, mechanism of action, pharmacology, and pharmacokinetics of NCS. The mode of action of NCS at the molecular level was first studied by my senior colleague, Yasushi Ono, MD, PhD, who demonstrated inhibition of DNA synthesis by NCS, and, at a higher dose, degradation of DNA as its primary mode of action. Dr. Kumagai explored the antitumor effect of NCS in vivo by using various murine models. We confirmed its extremely high potency in bacterial and cultured cell systems: its minimum inhibitory concentration was as low as 0.01 g  mL1, or less than 0.1 nM (24,25). One problem, however, was its very rapid clearance in vivo by both proteolytic degradation and renal excretion. We later found that this NCS, a small protein of 12 kDa, was being absorbed from the urinary bladder and returned to the blood circulation (by a vesicorenal recirculation mechanism) (26). Also, high accumulation in the urinary bladder supported its use for bladder cancer. Furthermore, intravenous administration by either a bolus or continuous infusion and by subcutaneous administration led to great differences in plasma drug concentration depends on the routes of administration. The pharmacokinetics of NCS or proteins in general were not fully clarified at that time. We later studied its pharmacokinetics and pharmacodynamics in more detail. On the basis of these data, we constructed computer-simulated compartment models for slow infusion of NCS via the carotid artery for use in therapy for brain tumors (two-compartment model) and leukemia (one-compartment model) (27,28). These models accounted for the extremely short half-life in blood and the urinary excretion. Inasmuch as a very low concentration of NCS was infused into the carotid artery for brain cancer, NCS in blood returning to the general circulation would be diluted to subtoxic levels, with concomitant proteolytic degradation helping keep its concentration at nontoxic levels. Later findings also showed that the enhanced permeability and retention (EPR) effect functions in brain cancer, because of the lack of the blood-brain barrier at tumor site. However, this clinical strategy, based on this unique pharmacokinetic characteristic of NCS, was not fully utilized for brain tumors, except for 19 cases of glioblastoma, for which we obtained good results (unpublished). The reason for this situation was related to economics, as discussed later. While I continued pharmacokinetics and pharmacodynamics studies of NCS in 1972, I had submitted a dissertation to Tohoku University Medical School for a doctoral degree in medicine that was based on study of NCS.

5. SMANCS IN CLINICS AND BEYOND: THE DISCOVERY OF THE EPR EFFECT The drawbacks of NCS, i.e., rapid renal clearance and proteolytic degradation, were overcome by conjugation of NCS with SMA polymer (20,29-31). Also, the antigenicity and immunogenicity against native NCS was almost fully eliminated (20,31) like pegylated proteins. In contract to the immunosuppression that many anticancer agents are known to cause, SMANCS stimulated natural killer cells, T cells, and macrophages, and induced interferon owing to its SMA component (32-35). Newly introduced styrene moiety of SMANCS and SMA also confer the albumin binding properties (35), thus albumin masks

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SMA-conjugates such as SMANCS, and thus they became more biocompatible (35). SMANCS thus became advantageous to NCS for various reasons. Although the biological, cytotoxic, and DNA inhibitory activities of SMANCS in vitro were almost equal to those of NCS, in that the molecular size was only 25% larger: 12 kDa versus 16 kDa, SMANCS was markedly different from the parental NCS, particularly in its hydrophobic nature and albumin-binding property. Binding to albumin would cause the Mr of SMANCS to become 90 kDa, so the apparent molecular size of SMANCS in blood plasma would exceed the molecular threshold of renal clearance, and SMANCS would not readily be cleared from the blood (31,36). SMANCS leaking out of blood vessels would be cleared via the lymphatic system, as described later, and would thus be lymphotropic. While we investigated these basic aspects, my colleague, Dr. Toshimitsu Konno of the First Department of Surgery of Kumamoto University Hospital, was trying to treat hepatic and biliary tumors by direct arterial injection via laparotomy and ligation of the hepatic artery. He asked me whether SMANCS would dissolve in Lipiodol, a lipid contrast agent. If it would, SMANCS would be an ideal candidate as a cancer treatment drug given by arterial injection, and he would inject SMANCS with Lipiodol. As that time, no anticancer agents were available that were suitable for use with Lipiodol. My answer was yes, it did dissolve in Lipiodol, so we prepared the SMANCS/Lipiodol solution. The next day, Dr. Konno injected this solution into the hepatic artery of rabbits with implanted VX-2 experimental tumors in the liver. When SMANCS/Lipiodol (1.0 mg  mL1) was injected arterially, we recognized its presence in the tumors using a soft X-ray system in the resected liver specimens, even without arterial ligation (37-41). Furthermore, no laparotomy was needed, because SMANCS/Lipiodol upon arterial injection spontaneously penetrated the tumor blood vessels of tissue into a remarkable manner, which was later interpreted as the EPR effect. This finding was quickly applied to clinical settings.

6. THE POWER OF INTRAARTERIAL INJECTION OF THE POLYMERIC DRUG SMANCSS/LIPIODOL At that time, there was virtually nothing to offer while there were the many hepatoma patients in Japan. One alternative was surgical resection, which would often result in a high and accelerated recurrence of residual tumor except only a few lucky patients . Methods for early diagnosis such as -fetoprotein (AFP) and computed tomography (CT) were just becoming available. Without treatment, patients died, usually within 3–4 months. Because of the poor diagnostic and treatment options, the late Professor Ikuzo Yokoyama, chairman of the Department of SurgeryI, asked me whether we could use SMANCS to treat a patient (a 56-year-old woman) by means of Seldinger‘s method via the femoral artery. With this method, neither laparotomy nor arterial ligation would be necessary, as we found earlier. The patient had an advanced hepatoma, a tumor more than 13 cm in diameter, and her life expectancy, even with blood transfusion and other treatments, was about 2 months, but no longer than 4–5 months. After Professor Yokoyama explained this new therapy to the patient and family, we performed this procedure under X-ray guidance, without complications. The patient appeared in the outpatient clinic for follow-up 3–4 months later. Dr. Konno, who was in charge of the patient, was shocked that the patient was still alive and looked very healthy,

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with no ascites or jaundice, which were the common manifestations of advanced hepatoma. CT examination showed that the hepatoma had markedly regressed, to an unprecedented extent (Figure 2).

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Figure 2. CT images of the liver for the first patient with a hepatoma treated with SMANCS. (A) Before SMANCS application, the dark area encircled by the dashed line is the liver tumor. (B) Five months after SMANCS treatment; (C) 17 months after SMANCS treatment. A marked reduction in tumor size can be seen. Lipiodol appears white high density area indicating tumor area and retain SMANCS.

Dr. Konno rushed into my office with the new and previous CT films, and both of us were of course quite excited. Professor Yokoyama, Dr. Konno, and I were convinced that SMANCS had some magical power. Within 1 year (1982), 22 patients received this treatment, and all but 2 showed a marked reduction in both tumor size and levels of the AFP tumor marker. This result was published in Japanese, journal Cancer and Chemotherapy (37), and about 1 year later, a more detailed paper on the clinical effect of SMANCS on hepatocellular carcinoma appeared in an English language journal (39). These results obviously encouraged all of us involved in development of the drug, and subsequent results were also published (3941). The extraordinary efficacy of SMANCS/Lipiodol was related to the truly precise tumorselective drug delivery, although it required arterial infusion via a designated artery. Along with our excitement about these clinical results, we were interested in a more quantitative evaluation of drug delivery via this technique. Therefore, to analyze the efficacy of this drug delivery, I synthesized a 14C-labeled Lipiodol moiety from [14C]linoleic acid and administered the 14C-labeled Lipiodol via the hepatic artery targeted to a tumor (VX-2) implanted in the liver of rabbits. Another graduate student, Ken Iwai surgeon, MD from Konno‘s laboratory helped me this part of extensive experiments. Analysis of radioactivity in the tumor confirmed that the highest count—more than 2000-fold—occurred in the tumor compared with that in blood. Furthermore, in contrast to the usual situation for lipid particles in normal tissue, 14C-labeled Lipiodol was not cleared from the tumor tissue as usually occurs via the lymphatic system (36,38). Indeed, in lymphology, Lipiodol is used to visualize the lymphatic duct and lymph nodes via an X-ray system or by lipid-specific staining. Lipid particles or

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macromolecules are usually cleared or recovered by the lymphatic system from the tissue interstitium, and the fact that Lipiodol remained in the tumor suggested an impaired lymphatic clearance in the tumor tissues. Furthermore, the distribution of 14C-labeled Lipiodol was only about a few percent of the injected doses in all normal organs such as the colon, kidney, and bone marrow, except for a relatively high value (10–15%) in the spleen and liver which were covered by the hepatic or splenic arteries near hepatic artery. This finding indicates that this intraarterial method of SMANCS/Lipiodol administration would almost completely eliminate the systemic adverse effects caused by drug deposition in normal tissues, while producing an extremely effective antitumor effect because the tumor-selective drug accumulation was so marked. The high radioactivity counts of labeled lipid in the liver and spleen (normal tissues) were much reduced within a few days, perhaps because of normal lymphatic clearance. Other explanations for the higher radio activity count in the liver may be the first-pass effect, because the artery used for the injection was the one supplying to the liver and the fact that lipid particles are usually recovered via the reticuloendothelial system of the liver and spleen.

7. BACK TO THE BASICS IN INFECTION, INFLAMMATION, AND CANCER: THE ROLES OF PROTEASES, REACTIVE OXYGEN SPECIES (ROS), AND REACTIVE NITROGEN SPECIES (RNS) IN PATHOGENESIS

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7a. Microbial Disease in the Absence of Microorganisms: Microbial Proteases as Pathogens Because I worked at Medical School, I was frequently asked to consult on various clinical problems. I was fortunate to interact with members of different clinical departments at the medical school: Internal Medicine (I/II), Surgery (I/II), Ophthalmology, Dermatology, and Obstetrics-Gynecology, and departments in the basic sciences, including Pharmacology, Anatomy and Pathology. Once, my colleague Professor Ryoichi Okamura, a professor of ophthalmology, showed me severe cases of corneal infection with Serratia marcescens and Pseudomonas aeruginosa, which did not respond to any antibiotics. The damage to the cornea was so severe and irreversible and the pain was so intense that some patients underwent extraction of the eyeball. Having some knowledge of bacterial proteases, I suggested that bacterial proteases could be the cause. In addition, Dr. Koki Matsumoto and Dr. Ryuji Kamata (who were then graduate students) came to my laboratory in the medical school to study whether serratia metalloproteinase triggered the kallikrein-kinin cascade, which was initiated by activation of the Hageman factor (or Factor XII) (42-46). Human humoral fluid contains no effective inhibitor of any of the proteases of Serratia or other bacteria. The end result is pain induced by bradykinin (or kinin) and involving vascular extravasation of plasma proteins. We were able to measure the extent of vascular leakage of plasma proteins by injecting Evans blue (which bound to albumin in vivo) into guinea pigs; the dye would leak into the interstitial space (outside blood vessels). The amount of Evans blue was quantified after extraction from the skin or dermal tissue with formamide. (This method would become an invaluable tool in quantification of vascular leakage from solid tumors during the elucidation of the EPR effect, as described later.) We then found that many microbial

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proteases activated one or more steps in the kallikrein-kinin cascade, i.e., activation of the Hageman factor, or direct liberation of bradykinin from kininogen. Then-graduate student Akhteruzzaman Molla (who is now Director of the Virus Research Laboratory of Abbott Laboratories, Chicago), from Bangladesh, made significant contributions to this work, after Dr. Matsumoto completed his PhD degree.

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Figure 3. Bradykinin in generation by protease and kallikrein-kinin cascade. A shows extravasation of Evans blue albumin complex induced by intradarmal injection of bradykinin and serratial 56K protease. B shows kallikrein → kinin cascade and steps that microbial proteases activate.

Extension of our research on bacterial proteases and house dust mite protease produced a surprising and intriguing finding: activation of influenza virus infectivity by cleavage of hemagglutinin on the surface of the virus. For this project, invaluable contributions of two graduate students—Takaaki Akaike and Keishi Maruo—should be mentioned (47,48). Dr. Akaike (now, Professor of Microbiology, Kumamoto University Medical School) also investigated the true cause of viral pneumonia, as well as the molecular mechanism of double infection with both bacteria and influenza virus, in which proteases caused a more than 100fold increase in viral infectivity. In our model, we administered, in addition to the virus, bacterial protease, at a dose of about 1 g, as a bacterial effector. The reproduction of virus was indeed markedly enhanced by proteolytic cleavage of the hemagglutinin of influenza virus, a process that is required for virus infectivity. A surprising finding was that house dust mite protease, which commonly occurs in household air or in the environment of areas inhabited by humans, did increase influenza virus infectivity 100-fold at the 1 g  mL1 level. This level is a likely concentration of mite protease found in ambient air being inhaled daily, which may be adsorbed on the upper tracheal epithelial surface (per cm2), the site of influenza virus entry (45-49). Therefore, in an influenza epidemic, more attention should be paid to exogenous proteases from various bacteria as well as dust derived mite proteases in addition to the endogenous serine-type proteases found in the body (e.g., kallikrein). This identification of activation of the kallikrein-kinin cascade by bacterial, fungal, and mite-derived proteases at different steps of the cascade was considered an important landmark in the field of kinin study, and it was a major reason for my receiving the Commemorative Gold Medal Award from the E. K. Frey–E. Werle Foundation of Munich, Germany, in 1998. The award was given on the basis of the recommendations of Professor Hans Fritz (Munich)

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and Professor Werner Müller-Esterl (since 2009, President of the Johann Wolfgang GoetheUniversity Frankfurt am Main) who were experts in this field, and I am most grateful to them (50). Later, in recognition of the Commemorative Gold Medal Award and my retirement, Biological Chemistry, a journal of the German Society for Biochemistry and Molecular Biology produced a special issue (November, 2004). In 1995, the Japan Society of Bacteriology had presented me with the Asakawa Award, its highest award, for the discovery of the pathogenic roles of bacterial proteases, particularly the finding of the mechanism of kinin generation and the involvement of proteases in the in vivo multiplication of influenza virus.

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7b. Microbial Disease in the Absence of Microorganisms: Endogenous Free Radicals as Pathogens In my department during my chairmanship, we pursued projects in multiple areas, including bacterial infection and proteases, viral infection and free radicals, and cancer chemotherapy and polymeric drugs. The interaction of different research fields yielded invaluable results, such as the role of polymer-conjugated superoxide dismutase (SOD) for the control of pathogenesis in influenza virus infection. This finding itself then led to the discovery of the superoxide anion radical (O2• ) as a pathogenic molecule and the first demonstration of the occurrence of O2•  in viral disease in the absence of virus (51-53). This concept went beyond the boundaries of the Postulates of Robert Koch, which required proof of the presence of defined microbial pathogens at the site of infection or in an ill subject (54). With reference to a different topic, viral infection triggers a number of events in host defense, or the immune response. One is the oxidative stress that is induced in influenza virus infection, which Dr. Linus Pauling first suggested. However, proving the presence of endogenous free radicals or ROS formation in animals and humans was quite difficult. One idea was to remove ROS, and then one could at least successfully control pathogenesis by using an enzyme, super oxide dismutase SOD with a molecular size of 30 kDa. In working toward this goal of proving the presence of these radicals, I had enough experience with chemical modifications of NCS, and I knew that the in vivo half-life of small proteins such as SOD would be too short, that native SOD would not work injected intravenously. Therefore, I designed an SOD to have a longer in vivo half-life by conjugating it with a biocompatible polymer, pyran copolymer [DIVEMA (divinyl ether and maleic anhydride copolymer)]. In collaboration with Dr. Takashi Hirano of Tsukuba, I prepared a pyran-SOD conjugate that had a more than 20-fold longer half-life in plasma after intravenous injection. Dr. Tatsuya Oda, my junior faculty, now Professor of Nagasaki University, and Akaike undertook experiment using influenza mouse model. Injecting this pyran-conjugated SOD into mice infected with influenza virus led to 98% survival, whereas almost all virus-infected control mice died 8–12 days after the infection began. It was interesting to follow the time course of viral yield in lungs of infected control mice: the maximal virus yield was obtained on days 4– 5, and from day 8 on mice started to die, but without detectable virus in the lung. By day 12, all control mice had died, but we found no virus in their lungs. This result means that the cause of viral death and the amount of virus found in the lung were unrelated. In contrast, when we scavenged the O2•  (or ROS) by means of pyran-SOD, the survival of mice

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improved greatly, which demonstrated the pathogenic role of O2•  in influenza virus infection. We then determined that the major source of O2•  generation was activation of xanthine oxidase in infected lung tissue. The results were published in Science and other prestigious journal (51-53). We successfully continued this line of research, and we later found that nitric oxide (NO) is generated in parallel with O2•  (55). Nitric oxide synthase (NOS) generates NO, mostly in infiltrated leukocytes. We then realized that O2•  and NO reacted extremely quickly, at a diffusion-limited rate, to form peroxynitrite (ONOO), which is highly oxidative and acts as a nitrating agent on proteins, nucleic acids, and lipids. We showed for the first time, in viral and bacterial infection models, that the nitration reaction and formation of mutants or virus and bacteria occurred at sites of infection (lesions) (55-57). This nitration is ubiquitous and affects many aromatic molecules, such as tyrosine (to produce nitrotyrosine) and purines (nitroguanosine), as reported earlier. More interesting and more important, we demonstrated that nitration of guanine at the eighth position led to formation of 8-nitroguanine. 8Nitroguanosine becomes a substrate of NOSs and cyt-P450 reductase etc, and then generate O2•  , thus lead to propagation reaction yielding ONOO and nitration of G, then generation of O2•  from 8-nitroguanine (57). This result confirmed that the mechanism of mutation occurred at the site of infection, and consequently it also supported inflammation-induced carcinogenesis (54,58,59). We reported that exposure to ONOO caused marked (severalfold) acceleration of viral mutation (57,59-62), as seen in influenza virus infection (56). Dr. Hideo Kuwahara, a former student in our laboratory, had found accelerated mutation in Salmonella in Ame‘s test , as well as drug-resistant mutants of Helicobacter pylori (at least a 7-fold higher frequency) in the presence of ONOO- at physiological and pathological concentration (59,60). Canolol, a phenolic compound that we found in crude rapeseed oil, blocked this ROS/RNS-induced mutation (59,60), as well as gastric carcinogenesis produced by a carcinogen plus H. pylori infection in a gerbil model, while it suppressed inflammation as revealed by collaboration with Dr. Shoei Tatematsu of Aichi Cancer Center of Nagoya (61). More recently, Sawa et al reported formal formation of 3‘ 5‘ cyclic-8 nitroguanosine which appears to have a significant role in intracellular signaling pathway (63).

8. CLARIFYING DETAILS OF THE EPR EFFECT: A UNIVERSAL SOLID TUMOR-TARGETING PRINCIPLE OF MACROMOLECULAR ANTICANCER AGENTS At about the same time, in the late 1980s, Dr. Yasuhiro Matsumura, who originally trained as a surgeon and is now at the National Cancer Center Hospital East, Japan, joined our laboratory to pursue a PhD degree in cancer research. He played a critical role in identifying bradykinin—as an effector responsible for facilitating fluid extravasation—in ascitic fluid in cancer patients (which occurs in carcinomatosis) (64). This finding stimulated us to investigate the mechanism of such extravasation in cancer tissue in greater detail, because this enhanced vascular permeability was thought to sustain rapid tumor growth by supplying oxygen and nutrients, which may be regarded as the true cause of sustained growth of cancer cells. However, we also thought to utilize this enhanced vascular permeability to control

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tumor growth, by suppressing kinin generation via either protease inhibitors or kinin antagonists. My prior knowledge of the chemical modification of proteins was an important element leading to the discovery of the EPR effect. Also, the method of quantitation of extravasation in infectious or inflammatory lesions as described earlier, could be readily applied to investigate extravasation in cancer tissue. Measuring Evans blue in tumor tissue could be viewed as corresponding to measuring delivery of macromolecular drugs of about 67 kDa to tumor tissues, or to accumulation of such drugs in tumor tissues, which we did not see in normal tissues (Figure 4A(1)). This observation was very intriguing. To validate such preferred accumulation of macromolecules in tumor tissue, we examined the effect of agents of different molecular sizes on tumor uptake of macromolecules in a more detailed manner. The first series of experiments, carried out in mice, involved injecting immunoglobulin (IgG, 160 kDa), transferrin (90 kDa), albumin (67 kDa), ovalbumin (47 kDa) and ovomucoid (28.8 kDa) from chicken egg white, and NCS (12 kDa). These substances were primarily labeled with diethylenetriaminepentaacetic acid (DTPA) (a chelating agent), followed by chelation of radioactive 51Cr, the use of this label having been described earlier by Professor Claude F. Meares of the University of California, Davis, California. In SMANCS (16 kDa), the two free amino groups of NCS were blocked by conjugation with SMA, so no free amino group was available. Therefore, SMANCS was first cross-linked with free L-lysine via its free carboxyl groups to form an amide linkage. DTPA was then added to the newly introduced amino group. With all these radioactive and biocompatible proteins in hand, Matsumura and I undertook extensive experiments. To my relief, my hypothesis that these natural proteins of more than 40 kDa would accumulate more selectively in cancer tissue was confirmed for all large proteins, but not for ovomucoids and NCS, both of which are small proteins. Small proteins were quickly excreted into urine, without uptake by tumors. However, when SMANCS was bound to albumin, its behavior was more like that of true macromolecules, near 90 kDa. We described these new findings in a manuscript that we submitted to the journal Cancer Research (65). I believed that this phenomenon of extravasation and accumulation of macromolecules in tumors and their prolonged residence time in plasma would merit an attractive appellation. I therefore coined the designation ―enhanced permeability and retention effect” of macromolecules in solid tumor tissues, or the EPR effect, which is now well accepted in the field of drug delivery, particularly in cancer targeting, for delivery of liposomes, micelles, antibodies, and DNA/carrier complexes to tumors (Figure 4). The EPR effect is more than just a passive targeting of drugs, however, because its definition includes a prolonged period of retention in tumor tissues. For instance, one can target any cancer drugs or imaging (contrast) agents to solid tumors if one injects them into a tumor-feeding artery; the drugs will be taken up more in tumor tissue but will disappear from the tumor within 5 min or so. This passive targeting is in clear contrast to the EPR effect, because the passive targeting is a temporary phenomenon. In fact, radiologists know this targeting as a tumor stain seen in routine angiography. In our 1986 Cancer Research paper (65), we also reported that intratumor retention of Evans blue-albumin injected into tumor showed was far more persistent than retention in normal tissues. The normal tissues cleared the Evans blue-albumin within a few days or so, and the agent was almost completely gone by 1 week. The Cancer Research paper of 1986 was accepted by the two referees, one of whom wrote a comment directly on the manuscript: ―Fantastic findings ! Send to the press

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immediately !.‖ This paper, authored by Dr. Matsumura and I, was published very quickly, without any revision required. We were, of course, extremely excited. On only a few other occasions in my career did I have papers published in a first-class journal without revision needed. The paper was well received, as was the advent of clinical development of SMANCS. Around this period we were receiving great many hepatoma patients from all over Japan and also from abroad. Maki Clinic in Kikuchi City took care these patients, and both Shojiro Maki, M.D., the director of clinic and who was also my student, and Dr. Konno were in charge of the clinical procedure. Cured hapatoma patients of San Antonio, Texas and State of Oklahoma nominated me to became an honorary mayor of San Antonio and an honorary citizen of the State of Oklahoma in 1989. Also, in 1997 the Princess Takamatsu Cancer Research Foundation in Tokyo gave me an award for academic excellence on the basis of development of SMANCS and discovery of the EPR effect in solid tumors.

Figure 4. The EPR effect in a tumor in vivo (A) and a schematic illustration of an enhanced EPR effect under angiotensin-II (AT-II)-induced hypertension (B) (reproduced with permission from ref (66). A: (1) S-180 tumors were implanted in the skin in mice, and when tumor reach to a palpable size Evans blue was injected intravenously. Dark blue spots in (1) demonstrate the tumor-selective accumulation of Evans blue-albumin; this means extravasation of Evans blue-albumin is observed as the EPR effect, which is not seen in normal tissue surrounding the tumors (67). In Figure 4, A-(2) and -(3), CT scan images of primary hepatoma after SMANCS/lipiodol injection via the hepatic artery which shows tumor selective drug (SMANCS/Lipidol) uptake by (EPR effect) in tumor as white area. CT scans were taken 2 days after administration and 6 months (Figure 4A (2)/(3)) after, respectively. B: The EPR effect does not occur in normal tissue but is observed in cancer tissue (65,66). Under AT-II-induced hypertension, drug delivery to tumor can be further augmented, with more delivery of the macromolecular drug to tumor, as seen in (on the right, which shows drug being pushed out) (67). The method is now being applied in clinical settings (66).

One great supporter of the EPR effect was Professor Ruth Duncan (at the University of Kiel, UK, then, now at the University of Cardiff). She became an enthusiastic locomotive engine in the field of polymer therapeutics, which is now also called nanomedicine. She and others, including Dr. William Regelson of the Virginia Commonwealth University College of

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Medicine in Richmond, who had been working on DIVEMA, also became good friends of mine during this time. Prof. Helmut Ringsdorf at University of Mainz, a renown polymer chemist and was a mentor of Ruth Duncan during her postdoc, also became a strong supporter of EPR effect. Dr. Duncan and I coorganized a few international symposiums on polymer therapeutics in London and Japan. She sent me a new postdoctoral fellow, Dr. Len Seymour (now Professor at the University of Oxford), to help continue investigations of the EPR effect and other developments in polymer therapeutics. I also received from her well-refined or discrete-sized copolymers of HPMA (hydroxypropyl methacrylate), which were prepared by the group led by Professor Karel Ulbrich of the Institute of Macromolecular Chemistry, in Prague, Czech Republic. After we radiolabeled these copolymers, we carefully examined their pharmacokinetics and retention in various tissues and tumors with a focus on their molecular size. We at Kumamoto also studied the kinetics of uptake of the copolymers by S180 tumors, particularly at early time points (i.e., within 1–6 h) (68); Dr. Duncan‘s group, then at the University of Birmingham, UK, performed similar studies with B16 melanoma (69). Other research groups in Tsukuba, Tokyo, and Kyoto have confirmed the EPR effect in different tumor models. Use of HPMA-copolymer of discrete different molecular sizes to analyze the EPR effect thus provided more refined data (36, 68-71). Another researcher, the late Professor Judah Folkman (1933–2008) at Children‘s Hospital Boston and Harvard Medical School, also became a strong supporter of the EFR effect. His lifelong study of angiogenesis, tumor neovascularization, and vascular permeability in cancer tissue are integral components of the field of the vascular biology of tumors that he developed. The angiogenesis and EPR effect are the most crucial aspect of tumor growth in view of supplying oxygen and nutrients. I was also most impressed by the excellent scanning electron microscope images of vasculature of tumor blood vessels by Professor Paul O‘Brien of the University of Melbourne then (now at Monash University Medical School), who reported leakage of polymers out of tumor blood vessels in Cancer Research in 1990 (72). We still collaborate with his students.

9. FACTORS FACILITATING THE EPR EFFECT We had previously determined that bacterial infection induced bradykinin via the kallikrein-kinin cascade, which is also responsible for pain and edema formation and frequently accompanies tissue degeneration. The cause of this bradykinin-related pain and edema was identical in both inflammation and cancer. That is, this same mechanism may indeed function in cancer tissue, inasmuch as we had identified excessive bradykinin levels in ascitic and pleural tumor fluids (64,73,74). These data were important because excessive bradykinin facilitates extravasation of fluid in the cavitary compartment and thus will play a role in ascitic and pleural fluid formation. Dr. Matsumura and Dr. Masami Kimura, who was then also a graduate student, in the Department of Surgery, clarified bradykinin formation in various cancerous ascitic and pleural fluids in many patients (73,74). Inhibition of bradykinin formation by inhibiting kallikrein with soybean trypsin inhibitor suppressed ascitic fluid accumulation. On the basis of these findings, I expected that activation of iNOS (the inducible form of NOS) and an accompanying NO generation would occur in tumor tissues. In one of our

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projects on infectious disease, we had developed a scavenger of NO, i.e., PTIO (2-phenyl4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) (75). Using PTIO, we found that NO was also involved in the EPR effect in solid tumors (76-79). Then, Jun Wu (a graduate student from China, who is now at the City of Hope National Medical Center in California) studied various vascular mediators as well as antagonists and inhibitors of inflammation such as aspirin, indomethacin, kinin antagonists, and L-NMMA (L-N-monomethyl arginine) and confirmed that these mediators affected the EPR effect as well (75-78). Thus, the EPR effect occurred in cancer as well as in inflammation (73,74-79). Among these mediators, collagenase and matrix metalloproteinase, activated by ONOO (which derived from the reaction of NO with O2• ), were also involved in the EPR effect (78,79). Other factors that were found to facilitate the vascular permeability of tumors include tumor necrosis factor-, vascular endothelial cell growth factor (VEGF), which was formally identified as vascular permeability factor by Dvorak and colleagues (80), and interleukin-12. I believe, however, that NO and bradykinin were the most important of all effectors. Therefore, the EPR effect is induced by multiple factors, and in fact it has now been demonstrated to function in tumors and inflammatory tissues, for delivery of various types of macromolecules and nanoparticles including antibodies, DNA/carrier complexes, and liposomes, and a considerable literature on the EPR effect has developed in recent ten years (Figure 5) and even bacteria (81, 82).

Figure 5. Citation frequency of papers on the EPR effect in solid tumors over time.

The Controlled Release Society awarded me the Nagai Innovation Award for Outstanding Achievement on my contribution in the targeted anticancer drug delivery (EPR mechanism) and invention of SMANCS, that is after following Robert Langer of MIT (2003). Detailed accounts of EPR effect have reviewed in many occasion (70,71,83-88).

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10. FURTHER ENHANCEMENT OF THE EPR EFFECT The vascular density of rapidly growing tumors such as hepatocellular carcinoma (primary liver cancer) and renal cell carcinoma is usually quite high, whereas that of other tumors, such as pancreatic and prostatic cancer, and metastatic liver cancers, is low. Such hypovascular tumors have lesser vascular density or vascular appearance upon angiography and may show a small EPR effect or low density as discussed earlier. People who do not accept the existence of the EPR effect have noted this point. A hypovascular nature indicates the presence of insufficient angiogenesis for tumor growth. However, blood vessels always occur wherever tissues grow; that is, no tissue lacks blood vessels (with an exception of cartridge). In the window chamber model of solid tumors in rats, one can observe very irregular blood vessels (89), and blood flow may be seen only once every 17 or 21 min unless blood pressure is raised. Hori and colleagues (89,90) also found that blood flow direction may change suddenly. Colloidal osmotic pressure in these solid tumors is believed to become very high and hence suppress penetration of drugs into tumor tissue. One argument proposes that mechanical tissue pressure is generated in an artificial chamber, where tumor cells have a doubling time of 24–48 h, and thus the tissue mass will fill up the chamber and compress the chamber space after a certain time interval, which would thereby impede vascular blood return or normal vascular physiology. In addition, most tumor cells have adapted hypoxic or anaerobic metabolism for energy production (known as the Warburg effect). Under such conditions, hypoxia-inducible factor, HIF-1, is known to be activated and to lead to generation of VEGF. Because the EPR effect is the result of vascular leakage of macromolecules from the luminal side to the tumor interstitium to support nutrients and oxygen supply, I initiated further investigations to enhance the EPR effect more by two practical methods for drug delivery to tumors. The first method involved artificially inducing the hypertensive state (e.g., 110–150 mmHg) with a slow intravenous infusion of angiotensin-II (AT-II). This pathophysiology of tumor vasculature was first described by Prof. Maro Suzuki (90). Drug in circulation would thus be more effectively pushed into tumor tissue because of the increased vascular pressure would open up only in the tumor vasculature due to incomplete vascular architecture such as lack of smooth muscle layer surrounding the blood vessels. Also, in an AT-II-generated hypertensive state, the endothelial cell-cell gap junctions in normal tissues would become tight, so fewer drugs would leak out of vessels in normal tissues in contract to tumor vessels which would be opened up. These experiments were carried out in 1991 by my then-student Chang Li (67), from China, who later received his PhD and MD degrees from Harvard and is now CEO and CSO of Boston Biomedical Inc. and was on the faculty at Harvard Medical School and CEO of ArQule. Clinical evaluation of this method was more recently conducted by my colleagues Dr. Akinori Nagamitsu and Dr. Khaled Greish in our Hakuaikai hospital in Kumamoto, with highly encouraging results that were recently published (66). Because of my pioneering work on polymeric drugs, particularly SMANCS, and my discovery of the EPR effect of macromolecular drugs in solid tumor, I received a Lifetime Achievement Award by Journal of Drug Targeting, Informa UK Ltd. (publisher) at the Royal Pharmaceutical Society, in Manchester, in 2007. Also, the Journal of Drug Targeting published a special issue to honor my award in 2007. The previous award winners are R. L. Juliano (USA,2004), A. Florence (UK, 2005) and H. Ringsdorf (Germany, 2006).

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The second method to enhance EPR effect was to utilize NO. We recently found the extremely interesting fact that drug delivery is enhanced by externally applied nitroglycerin. Nitroglycerin (91,92) has been used for more than 100 years to treat myocardial infarction and angina pectoris. Infarcted myocardial tissue becomes hypoxic, similar to many tumor tissues, so that both tissue oxygen (pO2) and pH values are low. Nitroglycerin is readily absorbed from the dermal surface into the circulation, and nitrite ion (NO2) is liberated from nitroglycerin (via denitrase) in the hypoxic infarcted tissue. NO2 is then converted to NO by nitrite reductase. As described earlier, NO is one of the major vascular permeability factors and facilitates the EPR effect, primarily in tumor tissue. This NO2 release thus occurs very similarly, or in the same manner, in both infarcted cardiac tissue and tumor tissue. The result is indeed enhanced drug delivery to tumors and an improved therapeutic effect. Takahiro Seki (our postdoctoral fellow), Jun Fang, and I recently reported this finding (92). My research activities, in addition to involving bacterial proteases and polymeric drugs, focused on clarifying the roles of endogenous free radicals (e.g., O2•  and NO•) in infection and cancer in the late 1980s to 2004 before the mandatory retirement from Kumamoto University. Consequently, I organized two international meetings on NO—one in 1997 in Kyoto, Japan, with Professor Noboru Toda (Shiga University) and Professor Salvador Moncada (The Wolfson Institute for Biomedical Research at University College London), and the other one, The 3rd International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide in 2004 in Nara, Japan, with Professor Mitsuhiro Yokoyama (Kobe University) and Professor Naoyuki Taniguchi (Osaka University). The Nitric Oxide Society, of which I was president for 2 years, published a special issue of the journal Nitric Oxide: Biology and Chemistry to honor my retirement in 2005. I am also helped to organize four other meetings in Kumamoto, Japan, in the past 7 years: 9th Meeting of the Society of Cancer Prevention of Japan in June, 2002; the 3rd Japan NO Meeting in May, 2003; the 76th Annual Meeting of the Japanese Society for Bacteriology in April, 2003; and the 23rd Meeting of the Japan Society of Drug Delivery System, in June, 2007.

11. SMA AS A VERSATILE MICELLE-FORMING AGENT Dr. Khaled Greish from Egypt joined my department as a graduate student in 2003. He had clinical experience (with a Master‘s degree in medicine) and a keen interest in new areas of cancer chemotherapy. I assigned him to investigate the possibility of forming micelles with anticancer agents using SMA, because from my earlier experience, I knew that SMA formed micelles. The primary issues were which drugs to encapsulate in the micelles, how to make the micelles, and what would be the characteristics of the SMA micelles. For a model, we chose the drugs doxorubicin and then pirarubicin (tetrahydropyranyl-doxorubicin, or THP). Both drugs formed useful micelles, with the THP micelles exhibiting slower drug release because they were more stable than were doxorubicin micelles. Indeed, SMA-THP micelles showed excellent in vivo antitumor activity (93-96). A few years before our investigations of SMA micelles, PEGylated ZnPP (PEG-ZnPP) had been shown to have excellent antitumor properties in vivo; our postdoctoral fellow from India, Dr. S. K. Sahoo (97), and Jun Fang in our laboratory described the in vivo evaluation (98). ZnPP is almost insoluble in water, but PEG-ZnPP and SMA-ZnPP micelles became

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water-soluble. ZnPP is essentially an inhibitor of heme oxygenase-1 (HO-1), which is also called heat shock protein (Hsp) 32 and is highly upregulated in most cancer cells. In these cells, HO-1 generates biliverdin from heme, and biliverdin is then oxidized to bilirubin. We realized that because bilirubin is a potent antioxidant, it confers antioxidative power to tumor cells to protect them against endogenous oxidants, which may come from leukocytes and anticancer agents. Administration of PEG-ZnPP to suppress bilirubin production in vivo would thus make targets more vulnerable to ROS, thus usefull as anticancer agent (98-101). More recently such encapsulation is incorporation of zinc protoporphyrin (ZnPP) into SMA- micelles after the work of PEG-ZnPP (95,102-104). Details such as drug release,stability, tumor targeting via the EPR effect, both therapeutic effect and toxicity in vivo were clarified by J. Fang, K. Greish, and A. K. Iyer (another graduate student from India). All the micellar drugs were better than the parental drugs in pharmacokinetics, therapeutic effect and toxicity. The SMA-pirarubicin micelle was the best among them: it had a longer (about 200 times) plasma circulation time and a higher (more than 20 times) tumor accumulation than the parent pirarubicin. In tumor-bearing mice, even at one-fifth of the maximal tolerable dose (i.e., a very low dose), SMA-pirarubicin micelles produced 100% survival at more than 200 days without detectable toxicity in S-180 tumor bearing mouse model. We also found that the micelles encapsulating ZnPP exhibited antitumor activity in vivo (95,98-104). These work continued up to now at Sojo University Faculty of Pharmaceutical Sciences in my new laboratory. Our report on the anticancer effects of the HO-1 inhibitor PEG-ZnPP drew the attention of many researchers throughout the world. One of them, Professor Peter Valent (Division of Hematology and Hemostaseology at the Medical University of Vienna), asked me to supply SMA-ZnPP and PEG-ZnPP. Also, from the Humboldt University of Berlin, Professor Beate Raeder (a laser biophysicist) asked me to collaborate. Both collaborations worked very well. Professor Valent‘s group published a paper on SMA-ZnPP and PEG-ZnPP that showed inhibition of HO-1 and downregulation of an oncogene in chronic myelogenous leukemia cells and other lymphocytic leukemia cells. Their approach was also effective against imatinib-resistant chronic myelogenous leukemia cells. Thus, HO-1 is an ideal molecular therapeutic target for inhibition without toxicity (102-104). Furthermore, SMA can encapsulate various fluorescent dyes such as fluorescein, rose bengal, and indocyanine green (as recently demonstrated by G. Bharate, a PhD student) as well as chlorophyll studied by Hideaki Nakamura, our junior faculty member) (unpublished data), and we expect future development along this line.

12. PROTEIN DRUGS, THEN AND NOW During development of proteinaceous pharmaceuticals in medicine, the possible antigenic nature of proteins has been the first concern, and the labile nature of proteins has been the second. We showed earlier that one could overcome these problems via polymer conjugation, including modification with SMA, which nullified the immunogenicity of SMANCS and prolonged its in vivo half-life (29-32,105-109). During this period, PEGylation was becoming a standard procedure used to reduce the immunogenicity of proteins. Before NCS was approved in 1971 as a therapeutic agent for treatment of leukemia and cancers of the

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gastrointestinal tract, pharmaceutical community involved had very little experience with or knowledge about protein drugs in technical and scientific issues, such as pharmacokinetics, tissue distribution, AUC (area under the concentration-time curve), and inactivation of protein drug.. The protein nature of NCS meant that proteolytic degradation would occur during sample preparation or processing, as well as on administration. Thus, NCS activity would drop rapidly if no protease inhibitor were used (29,30,105,108,109). My experience in Professor Feeney‘s laboratory helped me clarify these points. However, protein drugs were so new at that time that general acceptance was not so easy to achieve. NCS has, as mentioned earlier, extremely high activity at or less than the nanomolar range, and is thus very toxic unless the dosage is carefully controlled. Furthermore, its urinary excretion is extremely fast, with its molecular size of about 12 kDa, and its in vivo proteolytic degradation is also very rapid (26,109). It is thus essential for good therapeutic effect to maintain a meticulously controlled plasma concentration without over shooting the drug level to avoid adverse effect. We published these pharmacokinetic data for the theoretical calculation of infusing velocity for brain tumor via the intra carotid-arterial, and intravenous infusions velocity for leukimia, in which infusion of NCS was determined by considering rates of elimination (urinary excretion) and inactivation in the blood, and the IC50 etc (27,28,110). However, precise finetuning of dosing velocity was not popular among clinicians at that time. On the occasion of 30 years of the discovery of prototype proteinaceous antitumor agent NCS, we organized a symposium on NCS in Kumamoto in 1994. NCS had became a leading prototype of protein antitumor agents that contains unique endyene chromophore as active moiety that generates reactive oxygen species. Namely, proteinaceous antitumor agents included actinoxanthin in Moscow (Prof. Khoklov), macromomycin in Tokyo (Prof. Umezawa), and lymphomycerin and largomycin and others in Sendai (Prof. Ishida). The book on NCS describes the general characteristic of neocarzinostatin, the amino acid sequence and chemical structure of the protein portion and the chromophore, two-dimensional NMR study, X-ray crystallography, the mode of action at the molecular level, and the immunopotentiating effect. Clinical effects and side effects are also discussed, as well as development of the polymer conjugation for the development of anticancer polymer drug SMANCS and its clinical application (110). Our second macromolecular drug, SMANCS, which the Japanese Government approved for its use in 1993, was launched for marketing in 1994 by Yamanouchi Pharmaceutical Company, Tokyo, but its acceptance was also not so straightforward. One issue was that its approved route of administration was intraarterial, into the hepatic artery, for treatment of hepatocellular carcinoma (primary liver cancer). A second issue concerned the market size and sales volume. The financial incentive for any drug with a sales volume of less than $10 million or even $100 million dollars (US) per year is not attractive to most pharmaceutical companies, so that not much interest existed for marketing expansion or for treating different types of cancers. Thus, its clinical development other than hepatoma received no support. Today, a few decades later, protein drugs, many of which are PEGylated proteins, are attracting more attention than ever. According to Chemical and Engineering News of July 20, 2009, 4 of the top-selling 15 U.S. pharmaceutical products in 2008 were protein drugs. However, for the category of anticancer drugs of so called molecular target drugs, questions about cost/benefit issues prevail. Namely, many of the molecular target drugs do not satisfy the many patients. For instance, Tito Fojo and Christine Grady (111), and others (112,113)

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have expressed concerns about this issue, and The Lancet carried Editorial and other article on this matter (112,113). However, I can see great potential for development of anticancer drugs based on the EPR effect, which could target all tumors more selectively. Furthermore, we have now found ways to augment the EPR effect 2- to 3-fold by simple clinical manipulations, as discussed above. Therefore, macromolecular drugs may be more effective than low-molecular-weight drugs, because these EPR effect-based drugs utilize more universal and ubiquitous characteristics of solid tumors. Another issue is related to the system of anticancer drug development, about which one must think more carefully and wisely. For example, many drug-screening mouse models do not truly mimic highly mutated or genetically diversified human solid tumors, because mouse model tumor cell lines have features of primarily one clone and no host reactions (meaning no inflammation → no free radicals → no mutation → no genetic divergence) (114, 115). I believe that the design of synthetic polymeric drugs, which have much better potential of cost/benefit performance than the available contemporary protein drugs such as monoclonal antibodies, which are extremely expensive and selective to one specific target molecule (epitopic) in tumor cells, will be more economical and effective. Thus, these drugs will eventually be adopted for use in oncology clinics. In fact, many polymeric drugs are now in phase I and II trials in the United States, Japan, and Europe, and I am excited to see their clinical successes.

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ACKNOWLEDGMENTS I am greatly indebted to the long-term support of The Ministry of Education, Culture, Sports, Science, and Technology, Japan, for my Research Grants, such as Grants-in-Aid for Scientific Research on Cancer Priority Areas including (20015045), Scientific Research (C) (20590049), and others. I am also grateful to all my colleagues, in Kumamoto and elsewhere, who were not named in the text; to my wife Noriko; and to Judith B. Gandy, for long-term editing of my manuscripts.

REFERENCES [1] [2]

[3]

[4]

Maeda, H., Kumagai, K., and Ishida, N. (1966) Characterization of neocarzinostatin. J. Antibiot. Ser. A 19, 253-259. Maeda, H., and Kawauchi, H. (1968) A new method for the determination of Nterminus of peptido chain with fluorescein-isothiocyanate. Biochem. Biophys. Res. Comm., 31, 188-192 (3) Maeda, H., Ishida, N. Kawauchi, H. and Tuzimura, K. (1969) Reaction of fluorescein-isothiocyanate with protein and amino acids. Part I. J. Biochem., 65, 777783 Kawauchi, H., Tuzimura, K., Maeda, H. and Ishida, N. (1969) Reaction of fluoresceinisothiocyanate with protein and amino acids. Part II. J. Biochem., 66, 783-789

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Recollections of 45 Years in Research: From Protein… [5] [6] [7]

[8]

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[15] [16] [17]

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Meienhofer, J. Czombos, J. and Maeda, H. (1971) Reduction of disulfide bonds in liquid ammonia. J. Am. Chem. Soc., 93, 3080-3081 Meienhofer, J., Maeda, H., Glaser, C. B., Czombos, C., and Kuromizu, K. (1972) Primary structure of neocarzinostatin, an antitumor protein. Science 178, 875-876. Maeda, H., Glaser, C. B., Czombos, J., and Meienhofer, J. (1974) Structure of the antitumor protein neocarzinostatin. Purification, amino acid composition, disulfide reduction, and isolation and composition of tryptic peptides. Arch. Biochem. Biophys. 164, 369-378. Maeda, H., Glaser, C. B., Kuromizu, K., and Meienhofer, J. (1974) Structure of the antitumor protein neocarzinostatin. Amino acid sequence. Arch. Biochem. Biophys. 164, 379-385. Kuromizu, K., Abe, O., and Maeda, H. (1991) Location of the disulfide bonds in the antitumor protein, neocarzinostatin. Arch. Biochem. Biophys. 286, 569-573. Kuromizu, K., Tsunasawa, S., Maeda, H., Abe, O., and Sakiyama, F. (1986) Reexamination of the primary structure of an antitumor protein, neocarzinostatin. Arch. Biochem. Biophys. 246, 199-205 Maeda, H., Takeshita, J., and Yamashita, A. (1980) Lymphotropic accumulation of an antitumor antibiotic protein, neocarzinostatin. Eur. J. Cancer 16, 723-731. Maeda, H., Aikawa, S., and Yamashita, A. (1975) Subcellular fate of protein antibiotic neocarzinostatin in culture of a lymphoid cell line from Burkitt's lymphoma. Cancer Res. 35, 554-559. Sakamoto, S., Maeda, H., and Ogata, J. (1979) An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells. Experientia 35, 1223-1234. Takeshita, J., Maeda, H., and Koike, K. (1980) Subcellular action of neocarzinostatin: Intracellular incorporation, DNA breakdown and cytotoxicity. J. Biochem. 88, 10711080. Maeda, H. (1974) Preparation of succinyl neocarzinostatin. Antimicrob. Agents Chemoth. 5, 354-355 Maeda, H. (1974) Chemical and biological characterization of succinyl neocarzinostatin. J. Antibiotics, 27, 303-311 Maeda, H., Takeshita, J., and Kanamaru, R. (1979) A lipophilic derivative of neocarzinostatin: A polymer conjugation of an antitumor protein antibiotic. Int. J. Peptide Protein Res. 14, 81-87. Maeda, H., Takeshita, J., Kanamaru, R., Sato, H., Khatoh, J., Sato, H. (1979) Antimetastatic and antitumor activity of a derivative of neocarzinostatin: An organic solvent- and water-soluble polymer-conjugated protein. Gann 70, 601-606. Takeshita, J., Maeda, H., and Kanamaru, R. (1982) In vitro mode of action, pharmacokinetics, and organ specificity of poly(maleic acid-styrene)-conjugated neocarzinostatin, SMANCS. Gann 73, 278-284. Maeda, H., and Matsumura, Y. (1989) Tumoritropic and lymphotropic principles of macromolecular drugs. Crit. Rev. Ther. Drug Carrier Syst. 6, 193-210. Maeda, H., Ueda, M., Morinaga, T., and Matsumoto, T. (1985) Conjugation of poly (styrene-co-maleic acid) derivatives to the antitumor protein neocarzinostatin: Pronounced improvements in pharmacological properties. J. Med. Chem. 28, 455-461.

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[22] Takahashi, M. Toriyama, K. Maeda, H. Kikuchi, M. Kumagai, K. and Ishida, N. (1969) Clinical trials of a new antitumor polypeptide: Neocarzinostain. Tohoku J. Exp. Med., 98, 273-280 [23] Hiraki, K., Kamimura, O., Takahashi, I., Nagao, T., Kitajima, K., and Irino, S. (1973) Neocarzinostatin, a new chemotherapeutic approach to acute leukemia. Nouv Rev Fr Hematol 131, 445-451. [24] Ono Y., Watanabe, Y., Ishida, N. (1966). Mode of action of neocarzinostatin: inhibition of DNA synthesis and degradation of DNA in Sarcina lutea. Biochim Biophys Acta 119, 46-58. [25] Ono, Y., Ito, Y., Maeda, H. and Ishida, N. (1968) Mode of action of neo-carzino-stainmediated DNA degradation in Sarcina Lutea. Biochim. Biophys. Acta, 155, 616-618 [26] Maeda, H., Sakamoto, S., and Ogata, T. (1977) Mechanism of accumulation of the antitumor protein antibiotic neocarzinostatin in bladder tissue: Intravenous administration, urinary excretion, and absorption into bladder tissue. Antimicrob. Agents Chemother. 11, 941-945. [27] Maeda, H., Sano, Y., Takeshita, J., Iwai, Z., Kosaka, H., Marubayashi, T., and Matsukado, Y. (1981) A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin: Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery. Cancer Chemother. Pharmacol. 5, 243-249. [28] Maeda, H., Matsukado, Y., Iwai, Z., Uemura, S., Kuratsu, J., Takeshita, J., Sano, Y. (1982) Pharmacokinetic one-compartment model using neocarzinostatin as a prototype drug and its clinical application to chemotherapy for brain tumor. Part I. Theory and computer simulation for cerebrospinal infusion (in Japanese). Jpn. J. Cancer Chemother. 9, 1042-1045. [29] Maeda, H., and Takeshita, J. (1975) Degradation of neocarzinostatin by blood sera in vitro and its inhibition by diisopropyl fluorophosphate and N-ethylmaleimide. Gann, 66, 523-527. [30] Maeda, H. and Takeshita, J. (1976) Inhibitors of proteolytic enzymes prevent the inactivation by blood of the protein antibiotic neocarzinostatin and its succinyl derivative. J. Antibiotics, 29, 111-112 [31] Maeda, H., Matsumoto, T., Konno, T., Iwaki, K., and Ueda, M. (1984) Tailor-making of protein drugs by polymer conjugation for tumor targeting: A brief review on Smancs. J. Protein Chem. 3, 181-193. [32] Suzuki, F., and Kobayashi, M. (1997) Immunomodulating antitumor mechanism of SMANCS. Neocarzinostatin: The Past, Present, and Future of an Anticancer Drug (Maeda, H., Edo, K., and Ishida, N., Eds.) pp 167-186, Springer, Tokyo. [33] Masuda, E., and Maeda, H. (1997) Host-mediated antitumor activity induced by neocarzinostatin and its polymer-conjugated derivative in tumor-bearing mice. Neocarzinostatin: The Past, Present, and Future of an Anticancer Drug. (Maeda, H., Edo, K., and Ishida, N., Eds.) pp 187-204, Springer, Tokyo. [34] Oda, T., Morinaga, T., and Maeda, H. (1986) Stimulation of macrophage by polyanions and its conjugated proteins and effect on cell membrane. Proc. Soc. Exp. Biol. Med. 181, 9-17. [35] Kobayashi, A., Oda. T., and Maeda, H. (1988) Protein binding of macromolecular anticancer agent SMANCS: Characterization of poly(styrene-co-maleic acid)

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derivatives as an albumin binding ligand. J. Bioactive Compatible Polymers, 3, 319333. Maeda, H. (2001) SMANCS and polymer-conjugated macromolecular drugs: Advantages in cancer chemotherapy. Adv. Drug Deliv. Rev. 46, 169-185. Konno, T., Maeda, H., Yokoyama, I. et al (1982) Use of a lipid lymphographic agent, lipiodol, as a carrier of high molecular weight antitumor agent, SMANCS, for hepatocellular carcinoma. Cancer and Chemotherapy 9, 2005-2015 (in Japanese) Iwai, K., Maeda, H., and Konno, T. (1984) Use of oily contrast medium for selective drug targeting to tumor: Enhanced therapeutic effect and X-ray image. Cancer Res. 44, 2115-2121. Konno, T., Maeda, H., Iwai, K., et al (1983) Effect of arterial administration of highmolecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: A preliminary report. Eur. J. Cancer Clin. Oncol. 19, 1053-1065. Konno, T., Maeda, H., Iwai, K., et al (1984) Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer 54, 2367-2374. Maki, S., Konno, T., and Maeda, H. (1985) Image enhancement in computerized tomography for sensitive diagnosis of liver cancer and semiquantitation of tumor selective drug targeting with oily contrast medium. Cancer 56, 751-757. Matsumoto, K., Yamamoto, T., Kamata, R., and Maeda, H. (1984) Pathogenesis of serratial infection: Activation of the Hageman factor-prekallikrein cascade by serratial protease. J. Biochem. 96, 739-749. Kamata, R., Yamamoto, T., Matsumoto, K., and Maeda, H. (1985) A serratial protease causes vascular permeability reaction by activation of the Hageman factor-dependent pathway in guinea pigs. Infect. Immun. 48, 747-753. Molla, A., Yamamoto, T., Akaike, T, Miyoshi, S., and Maeda, H. (1989) Activation of Hageman factor and prekallikrein and generation of kinin by various microbial proteinases. J. Biol. Chem. 264, 10589-10594. Maeda, H. (1996) Role of microbial proteases in pathogenesis. Microbiol. Immunol. 40, 685-699. Maeda, H. (2002) Microbial proteinases and pathogenesis of infection. Wiley Encyclopedia of Molecular Medicine (Creighton, T. E., Ed.) pp 2663-2668, Volume 4, John Wiley & Sons, New York. Akaike, T., Molla, A., Ando, M., Araki, S., and Maeda, H. (1989) Molecular mechanism of complex infection by bacteria and virus analyzed by a model using serratial protease and influenza virus in mice. J. Virol. 63, 2252-2259. Maruo, K., Akaike, T., Inada, Y., Ohkubo, I., Ono, T., and Maeda, H. (1993) Effect of microbial and mite proteases on low and high molecular weight kininogens. J. Biol. Chem. 268, 17711-17715. Akaike, T., Maeda, H., Maruo, K., Sakata, Y., and Sato, K. (1994) Potentiation of infectivity and pathogenesis of influenza A virus by a house dust mite protease. J. Infect. Dis. 170, 1023-1026. Frits, H., and Travis, J. (2004) Hiroshi Maeda—40 years of research. Reflections on the occasion of his retirement and 65th birthday. Biol. Chem. 385, 987-988.

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[51] Oda, T., Akaike, T., Hamamoto, T., Suzuki, F., Hirano, T., and Maeda, H. (1989) Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymerconjugated SOD. Science 244, 974-976. [52] Akaike, T., Ando, M., Oda et al (1990) Dependence on O2 generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J. Clin. Invest. 85, 739745. [53] Maeda, H., and Akaike, T. (1991) Oxygen free radicals as pathogenic molecules in viral diseases. Proc. Soc. Exp. Biol. Med. 198, 721-727. [54] Maeda, H. (2000) Paradigm shift in microbial pathogenesis: An alternative to the Koch-Pasteur paradigm in the new millennium. Abstr. for the 13th International Congress of The International Organization for Mycoplasmology, Fukuoka, Japan, 35. [55] Akaike, T., Noguchi, Y., Ijiri, S. et al (1996) Pathogenesis of influenza virus-induced pneumonia: Involvement of both nitric oxide and oxygen radicals. Proc. Natl. Acad. Sci. U.S.A. 93, 2448-2453. [56] Akaike, T., Fujii, S., Kato, A. et al (2000) Viral mutation accelerated by nitric oxide production during infection in vivo. FASEB J. 14, 1447-1454. [57] Sawa, T., Akaike, T., Ichimori, K. et al (2003) Superoxide generation mediated by 8nitroguanosine, a highly redox-active nucleic acid derivative. Biochem. Biophys. Res. Comm., 311, 300-306. [58] H. Maeda and T. Akaike (1998) Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Moscow), 63, (No.7) 1007-1017 [59] Kuwahara, H., Kariu, T., Fan, J., and Maeda, H. (2009) Generation of drug-resistant mutants of Helicobacter pylori in the presence of peroxynitrite, a derivative of nitric oxide, at pathophysiological concentration. Microbiol. Immunol. 52, 1-7. [60] Kuwahara, H., Kanazawa, A., Wakamatsu, D., Morimura, S., Kida, K., Akaike, T., and Maeda, H. (2004) Antioxidative and antimutagenic activities of 4-vinyl-2, 6dimethoxyphenol (canolol) isolated from canola oil. J. Agric. Fd. Chem., 52, 43804387 [61] Cao, X., Tsukamoto, T., Seki, T. et al (2008) 4-Vinyl-2,6-dimethoxyphenol (canolol) suppresses oxidative stress and gastric carcinogenesis in Helicobacter pylori-infected carcinogen-treated Mongolian gerbils. Int. J. Cancer 122, 1445-1454. [62] J. Yoshitake, T. Akaike, T. Akuta, F. Tamura, T. Ogura, H. Esumi and H. Maeda: Nitric oxide as an endogenous mutagen for Sendai virus without antiviral activity. J. Virol., 78, 8709-8719 (2004) [63] Sawa, T., Zaki, M., H., Okamoto, T. et al (2007) Protein S-guanylation by the biological signal 8-nitroguanosine 3‘,5‘-cyclic monophosphate. Nature Chem. Biol.3, 727-735. [64] Maeda, H., Matsumura, Y., and Kato, H. (1988) Purification and identification of [hydroxprolyl3]bradykinin in ascetic fluid from a patient with gastric cancer. J. Biol. Chem. 263, 16051-16054. [65] Matsumura, Y., and Maeda, H. (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387-6392. [66] Nagamitsu, A., Greish, K., and Maeda, H. (2009) Elevating blood pressure as a strategy to increase tumor targeted delivery of macromolecular drug SMANCS: Cases of advanced solid tumors. Jpn. J. Clin. Oncol., 39,756-766.

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[67] Li, C. J., Miyamoto, Y., Kojima, Y., and Maeda, H. (1993) Augmentation of tumor delivery of macromolecular drugs with reduced bone marrow delivery by elevating blood pressure. Br. J. Cancer 67, 975-980. [68] Noguchi, Y., Wu, J., Duncan, R. et al (1998) Early phase tumor accumulation of macromolecules: A great difference in clearance rate between tumor and normal tissues. Jpn. J. Cancer Res. 89, 307-314. [69] Seymour, L. W., Miyamoto, Y., Maeda, H., Brereton, M., Strohalm, J., Ulbrich, K., and Duncan, R. (1995) Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier. Eur. J. Cancer 31, 766-770. [70] Maeda, H., Seymour, L. W., and Miyamoto, Y. (1992) Conjugates of anticancer agents and polymers: Advantages of macromolecular therapeutics in vivo. Bioconj. Chem. 3, 351-362. [71] Maeda, H., Wu, J., Sawa, T., Matsumura, Y., and Hori, K. (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J. Controlled Release 65, 271-284. [72] Skinner, S. A., Tutton, P. J. M., and O‘Brien, P. E. (1990) Microvascular architecture of experimental colon tumors in the rat. Cancer Res. 50, 2411-2417. [73] Matsumura, Y., Kimura, M., Yamamoto, T., Maeda, H. (1988) Involvement of the kinin-generating cascade in enhanced vascular permeability in tumor tissue. Jpn. J. Cancer Res. 79, 1327-1334. [74] Matsumura, Y., Maruo, K., Kimura, M., Yamamoto, T., Konno, T., and Maeda, H. (1991) Kinin-generating cascade in advanced cancer patients and in vitro study. Jpn. J. Cancer Res. 82, 732-741. [75] Akaike, T., Yoshida, M., Miyamoto, Y., Sato, K., Kohno, M., Sasamoto, K., Miyazaki, K., Ueda, S., and Maeda, H. (1993) Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/･NO through a radical reaction. Biochemistry, 32, 827-832. [76] Maeda, H., Noguchi, Y., Sato, K., Akaike, T. (1994) Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn. J. Cancer Res. 85, 331-334. [77] Maeda, H., Wu, J., Okamoto, T., Maruo, K., and Akaike, T. (1999) Kallikrein-kinin in infection and cancer. Immunopharmacology ,43, 115-128. [78] Wu, J., Akaike, T., and Maeda, H. (1998) Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger. Cancer Res. 58, 159-165. [79] Wu, J., Akaike, T., Hayashida, K., Okamoto, T., Okuyama, A., and Maeda, H. (2001) Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinase. Jpn. J. Cancer Res. 92, 439-451. [80] Senger, D. R., Galli, S. J., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., Dvorak, H. F. (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science, 219, 983-985. [81] Kimura N, Taniguchi S, Aoki K, Baba T. Selective localization and growth of Bifidobacterium bifidum in mouse tumors following intravenous administration. Cancer Res. 40. 2060-2068 (1980).

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[82] Zhao M, Yang M, Ma H, Li X, Tan X, Li S, Yang Z and Hoffman R M. Targeted therapy with a salmonella typhimurium leucine-arginine auxotroph cures orthotopic human breast tumors in nude mice. Cancer Res. 66, 7647-7652 (2006). [83] H. Maeda, T. Sawa, and T. Konno: Mechanism of tumor-targeted deliverly of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J. Cont. Release, 74, 47-61 (2001). [84] H. Maeda, G. Y. Bharate, J.Daruwalla, Polymeric drugs and nanomedicines for efficient tumor targeted drug delivery based on EPR-effect. Eur. J. Pharm. Biopharm. 71, 409-419, (2009). [85] T. Seki, J. Fang, H. Maeda: Tumor targeted macromolecular drug delivery based on the enhanced permeability and retention effect in solid tumor. In Pharm. Perspective of Cancers Therapeutics (eds. Y. Lu and R.I. Mahato), AAPS Springer Press, New York, 94-120 (2009). [86] A.K. Iyer, K. Greish, J. Fang, R. Murakami and H. Maeda: High-loading nanosized micelles of copoly(styrene–maleic acid)–zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor. Biomaterials, 28, 1871-1881(2007). [87] K. Greish, J. Fang, T. Inuzuka, A. Nagamitsu and H. Maeda: Macromolecular anticancer therapeutics for effective solid tumor targeting: Advantages and prospects. Clinical Pharmacokinetics, 42, 1089-1105 (2003). [88] Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting. In: Weber G eds .Advances in Enzyme Regulation: Oxford, UK, Elsevier Science Ltd. 2001; 41, 189207. [89] Hori, K., Suzuki, M., Tanda, S., Saito, D., Shinozaki, M., and Zhang, Q. H. (1991) Fluctuations in tumor blood flow under normotension and the effect of angiotensin ІІinduced hypertension. Jpn, J. Cancer Res. 82, 1309-1316. [90] Suzuki, M., Hori, K., Abe I., Saito, S., and Saito, H., (1981) A new approach to cancer chemotherapy: a selective enhancement of tumor blood flow with angiotensin II. J. Natl. Cancer Inst. 67, 663-669. [91] Maeda H, Seki T, Fang J. (2008) Enhanced tumor delivery of macromolecular antitumor-drugs by topical application of nitroglycerin on superficial tumors. Abst. 67th Annual Meeting of the Jpn. Cancer Assoc. No. P-518, p.213 [92] Seki, T., Fang, J., and Maeda, H. (2009) Enhanced delivery of macromolecular antitumor drugs to tumors by nitroglycerin application. Cancer Sci. 100, 2426-2430. [93] Greish, K., Nagamitsu, A., Fang, F., and Maeda, H. (2005) Copoly(styrene-maleic acid)-pirarubicin micelles: High tumor-targeting efficacy with low toxicity. Bioconj. Chem.16, 230-236. [94] Greish, K., Sawa, T., Fang, J., Akaike, T., and Maeda, H. (2004) SMA- doxorubicin, a new polymeric micellar drug for effective anticancer targeting. J. Controlled Release 97, 219-230. [95] Iyer, A. K., Greish, K., Seki, T., Okazaki, S., Fang, J., Takeshita, K., and Maeda, H. (2007) Polymeric micelles of zinc protoporphyrin for tumor targeted delivery based on EPR effect and singlet oxygen generation. J. Drug Target. 15, 496-506. [96] J. Daruwalla, K. Greish, C. M. Wilson, V. Muralidharan, A. Iyer, H.Maeda, C. Christophi Styrene maleic acid-pirarubicin disrupts tumor microcirculation and

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enhances the permeability of colorectal Liver Metastases, J. Vascu. Res., 46, 218-228 (2009) Sahoo, S. K., Sawa, T., Fang, J., Tanaka, S., Miyamoto, Y., Akaike, T., and Maeda, H. (2002) Pegylated zinc protoporphyrin: A water-soluble heme oxygenase inhibitor with tumor-targeting capacity. Bioconj. Chem. 13, 1031-1038. Fang, J., Sawa, T., Akaike, T., Akuta, T., Sahoo, S. K., Griesh, K., Hamada, A., Maeda, H. (2003) In vivo antitumor activity of pegylated zinc protoporphyrin: Targeted inhibition of heme oxygenase in solid tumor. Cancer Res. 63, 3567-3574. Doi, K., Akaike, T., Fujii, S., Tanaka, S., Ikebe, N., Beppu, T., Shibahara, S., Ogawa, M. and Maeda, H. (1999) Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth. Br. J. Cancer, 80, 1945-1954. (100)J. Fang, T. Sawa, T. Akaike, K. Greish, and H. Maeda: Enhanced chemotherapeutic effect against tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin in combination with anticancer agents. Int. J. Cancer, 109, 1-8 (2004) J. Fang, T. Akaike, and H. Maeda: Antiapoptotic role of heme oxygenase and its potential as an anticancer target. Apoptosis, 9, 27-35 (2004) M. Regehly, K. Greish, F. Rancan, H. Maeda, F. Böhm and B. Röder: Water-soluble polymer conjugated of ZnPP for photodynamic tumour therapy. Bioconj. Chem., 18, 494-499 (2007) Mayerhofer, M., Gleixner, K. V., Hörmann, G., Sonneck, K., Aichberger, K. J., Ott, R. G., Greish, K., Nakamura, H., Derdak, S., Samorapoompichit, P., Pickl, W. F., Sexl, V., Esterbauer, H., Sillaber, C., Maeda, H., and Valent, P. (2008) Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: A novel approach to overcome resistance against imatinib. Blood 111, 2200-2210. Hadzijusufovic, E., Rebuzzi, L., Gleixner, K. V., Ferenc, V., Kondo, R., Gruze, A., Kneidinger, M., Krauth, M.-T., Mayerhofer, M., Samorapoompichit, P., Greish, K., Pickl, W. F., Maeda, H., Willmann, M., and Valent, P. (2008) Targeting of heat-shock protein 32/heme oxygenase-1 in canine mastocytoma cells is associated with reduced growth and induction of apoptosis. Exp. Hematol. 36, 1461-1470. H. Maeda, N. Yamamoto and A. Yamashita (1976) Fate and distribution of [14C] succinyl neocarzinostatin in rats. Europ. J. Cancer, 12, 865-870 H. Maeda, M. Kimura, I. Sasaki, Y. Hirose and T. Konno (1992) Toxicity of bilirubin and detoxification by PEG-bilirubin oxidase conjugate: A new tactic for treatment of jaundice. In Poly (Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications (ed. J. M. Harris) Plenum Press, New York, p. 153-169 M. Kimura, Y. Matsumura, T. Konno, Y. Miyauchi and H. Maeda: Enzymatic removal of bilirubin toxicity by bilirubin oxidase in vitro and excretion of degradation products in vivo. Proc. Soc. Exp. Biol. Med., 195, 64-69 (1990) H. Maeda and T. Konno: Metamorphosis of neocarzinostatin to SMANCS −Chemistry, pharmacology and clinical effect of the first prototype anticancer polymer therapeutic− In Neocarzinostatin: The Past, Present, and Future of an Anticancer Drug. (eds. H. Maeda, K. Edo and N. Ishida) Springer-Verlag, Tokyo, p. 227-267 (1997)

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[109] H. Maeda, T. Akaike, Y. Sakata and K. Maruo: Role of bradykinin in microbial infection: Enhancement of septicemia by microbial proteinases and kinin. In Agents and Actions Supplements 42, Proteases, Proteases Inhibitor and Protease-Derived Peptides: Importance in Human Pathophysiology and Therapeutics. (eds. J.C.Chironis and J.E. Repine) Birkhauser Verlag AG, Switz., p.159-165 (1993) [110] H. Maeda, K. Edo and N. Ishida eds. (1997) Neocarzinostatin: The Past, Present, and Future of an Anticancer Drug. Springer-Verlag, Tokyo, pp. 1-289 [111] Fojo, T., and Grady, C. (2009) How much is life worth: Cetuximab, non-small cell lung cancer, and the $440 billion question. J. Natl. Cancer Inst. 101, 1044-1048. [112] Hind, D., Pilgrim, H., and Ward, S. (2007) Questions about adjuvant trastuzumab still remain. Lancet 369, 3-5. [113] Editorial (2008) Welcome clinical leadership at NICE. Lancet 372, 601. [114] Sjöblom, T., Jones, S., Wood, L. D. et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-274. [115] Shah, S. P., Morin, R. D., Khattra, J., et al and Aparicio, S. (2009) Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution Nature 461, 809-813.

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Chapter 2

EDUCATIONAL CHANGES IN PREVENTING INFECTION RISK DUE TO OCCUPATIONAL BLOOD-BORNE EXPOSURE Emanuele Amodio1, Nino Romano2 and Maria Antonella Di Benedetto3

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1

Emanuele Amodio, Medical Doctor, Specialist in Hygiene and Preventive Medicine, University of Palermo, Department for Health Sciences Promotion 2 Nino Romano, Medical Doctor, full professor of Hygiene and Preventive Medicine, University of Palermo, Department for Health Sciences Promotion 3 Maria Antonella Di Benedetto, Biologist, University of Palermo, Department for Health Sciences Promotion

1. BACKGROUND With the emergence of AIDS in the early 1980s, concerns about the transmission of blood-borne pathogens began to grow in the workplace including in the healthcare setting. Responding to these concerns, the Centers for Disease Control and Prevention (CDC) in the USA have issued Universal Precautions [1], followed by Standard Precautions [2], aiming to protect healthcare workers (HCWs) from exposure to blood-borne pathogens. Standard Precautions combine the major features of Universal Precautions and Body Substance Isolation [3] and are based on the principle that blood, body fluids, secretions, excretions except sweat, non-intact skin, and mucous membranes may contain transmissible infectious agents. An accidental exposure to blood or other body fluids in a healthcare setting constitutes a risk of transmission of HIV and other blood-borne pathogens such as HBV and HCV [4, 5]; in addition, such exposure can cause tremendous anxiety and can be a life changing experience. Indeed, assessing the risk involved in an accident and counselling the patient could be complicated. Within a limited period of time, information of the victim‘s and the

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E. Amodio, N. Romano and M. Antonella Di Benedetto

source‘s serology status has to be collected and possibly complemented by additional laboratory tests to take appropriate preventive measures. The World Health Organization (WHO) estimates that 3 million percutaneous exposures occur annually among 35 million HCWs and that as a consequence an estimated 66,000 hepatitis B, 16,000 hepatitis C and up to 1,000 HIV infections occur each year [6]. Most HCWs today are immune to HBV as a result of pre-exposure vaccination [7]. However, without postexposure prophylaxis, there is a 6% to 30% risk that a susceptible exposed HCW will be infected with HBV [4]. The precise number of healthcare personnel with occupationally acquired HCV infections is unknown. Prospective studies show that the risk for HCV transmission following percutaneous exposure to an HCV-positive source is approximately 1.8% (range 0%–7%) [4] and the average risk for HIV transmission after a percutaneous exposure is estimated to be approximately 0.3% [8]. The primary goal of infection control is to protect HCWs from acquiring a serious viral infection. For this reason, the CDC recommends the use of Standard Precautions (SP) to protect healthcare workers from the risk of acquiring nosocomial pathogens such as HIV, HBV and HCV. Its use is strongly recommended because it is impossible to identify all those patients HIV positive, and cost of routine HIV testing is more expensive than consistently practicing SP [9]. SP are also intended to protect patients by ensuring that HCWs do not carry infectious agents to patients on their hands or via equipment used during their care. Improvement of hand hygiene, with the aim of minimizing nosocomial infections, is a high priority of the WHO; i.e. microorganisms such as Staphylococcus aureus, found in 10% to 78% of healthcare workers, can survive for over 2 hours on the hands [10]. Despite recognition of the importance of standard precautions, studies have shown that the adherence levels are unsatisfactory and compliance with SP among HCWs remains low although in both developing [11] and developed countries [12] the level of adherence varies according to professional category [13,14]. Some studies documented aspects that were especially neglected including hand washing, cleaning of surfaces and cleaning of shared materials. Individual, work-related and organizational factors have been identified as the reasons for poor adherence to SP such as, for example, misinformation, insufficient time and unavailability of materials (soap, sharps containers, disinfectants); moreover, discrimination toward HIV-positive patients may contribute to inappropriate SP use because of exaggerated fears [15].

2. STANDARD PRECAUTIONS Standard Precautions include a group of infection prevention practices that apply to all patients, regardless of suspected or confirmed infection status, in any setting in which healthcare is delivered. The main recommendations include: a) the use of personal protective equipment (PPE) such as gloves, gown, mask, eye protection or face shield whenever there is a possibility of contact with organic secretions

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b) hand hygiene c) cleaning of surfaces d) proper disposal of sharp objects. The adoption of SP during patient care is determined by the nature of the HCWs-patient interaction and the extent of anticipated blood or body fluid exposure [16]. For some interactions, such as taking of a blood sample, only gloves may be needed; during other interactions, for example, intubation, use of gloves, gown, face shield and goggles is necessary. Compliance with standard precautions during intubation is very important especially under emergency circumstances when infectious agents may not be suspected, but later are identified (e.g., SARS-CoV, Mycobacteria tuberculosis, Neisseria meningitidis) [16].

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1. Use of Personal Protective Equipment The proper use of personal protective equipment (PPE) is one of the preventive practices strongly recommended by the Centers for Disease Control and Prevention (CDC). The underlying principle of this last statement is that, since many patients with infections are not recognized, all body fluids are potentially infectious. According to the U.S. Occupational Safety and Health Administration (OSHA), PPE refers to ―specialized clothing or equipment worn by an employee for protection against infectious materials‖. In this way, PPE acts as a physical barrier that blocks the exposure to potentially infectious body fluids avoiding their contact with face, hands and other exposed skin (or mucous membranes) during patient care activities. Moreover, wearing PPE can reduce the chance of contaminating sanitary environment lowering the risk of infectious spread among patients. For these reasons, the use of gloves, gowns/aprons, masks/respirators and goggles/face shield should be strongly encouraged in healthcare settings.

1. Gloves Gloves are the most common type of PPE used in healthcare settings. Just more than one century ago, Semmelweiss recognized that hands of healthcare workers may be a major source of nosocomial infections and it has been established that the number of microorganisms on the hands steadily increases on average 16 units for minute on the nongloved hands [17,18] during performance of healthcare tasks. Otherwise, gloving is associated with a marked reduction of bacterial contamination and colonization of hands. According to previous considerations, international literature agrees that wearing gloves is a main practice for both prevent hand contamination and reduce transmission of pathogens. OSHA mandates gloves to be worn by HCWs during any patient care. Nowadays, several different types of gloves are available on the market in order to reach the best solution for workers and patients. Allergic problems linked to the use of gloves in latex were solved limiting latex products and using gloves made with nitrile, vynil or other materials. When invasive patient procedures are needed, sterile surgical gloves can be used by healthcare workers and during some surgical procedures, two pairs of gloves can minimize infectious risks. Gloving significantly reduces the risk of exposures but in no case wearing gloves can provide a complete protection of hands [19] and when gloves have not been properly removed

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a further contamination of skin is possible in up to 29.4% of subjects [20]. Moreover, several authors reported glove cross-contamination rates of 39% to 64% [21, 22] suggesting a high risk of healthcare associated infections in patients. Biological risks can greatly increase because of the uncompliance with gloving among HCWs and suboptimal rates of glove utilization were still worldwide reported, from 13.5% in Malaysia [23], 39% in China [24], 58.8% in Turkey [25] and up to 62% in USA [26].

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2. Gowns/Aprons Gowns/aprons are used to protect exposed skin and clothing during activities that may generate splashes or sprays of biologic, physical and chemical hazards. Aprons are generally preferred when limited contamination is anticipated whereas gowns which cover front and back torso as well as arms should be used when considerable contamination of the body can be expected. Sterile gowns are used when invasive procedure need to be performed and waterproof gown should be worn when fluid penetration is likely to occur. Several studies show that gowns are effective barriers, decreasing dissemination of microorganisms and being cost saving by averting nosocomial infections and their associated costs of treatment [27, 28]. Some other authors highlight that although gowns were found to not decrease hospital infection rates [29] they help to increase compliance with other infection control measures, such as handwashing and gloving [30] to 84% among UK general practitioners in 2004 [33]. 3. Facemasks and Respirators Facemasks and respirators intend to prevent the spread of germs from patients to HCWs, protecting respiratory tract and mucous membranes of mouth and nose. Both devices may also reduce the exposure of others to HCW‘s saliva and respiratory secretions. Facemasks do not form a tight seal on the face and do not provide complete protection because of the loose fit between the surface of the facemask and face, they are used to help wearers from coming into contact with germs by blocking large-particle droplets transmitted by cough, sneezes or certain medical procedures. Differently, most respirators (e.g. N95 or higher filtering piece respirator) are designed to achieve a very close facial fit and a more efficient filtration of very small particles that may be in the air. For this reason, CDC does not recommend respirators for children or people with facial hair because a proper fit cannot be achieved. However, respirators make it more difficult to communicate or breathe for long period of time. In this way, HCWs generally do not comply with facemask/respirator use and a recent review on this topic has reported a mean compliance rate of 30% (range 4-55%) [31]. 4. Goggles and Face Shields Goggles and face shields provide barrier protection for eye and/or other facial areas. Goggles are devices designed to fit wearer‘s face blocking splashes, sprays and respiratory droplets. Nowadays, new styles of goggles can be fitted over glasses and they also can be directly or indirectly vented on the side to reduce fogging. Face shields typically offer coverage from forehead to below the mouth and prevent fluid penetration. However, full face masks covering from forehead to below the chin are available when copious exposure is

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attended [34]. Several studies reporting compliance rates for the use of eye protection ranged from 0% [35] to 92% [36] with a mean of 38% [31]. The proper use of PPE is essential in minimizing health risks and requires of some knowledge that should be kept in mind: 1. Almost all PPE is disposable and is designed to be used only once for contact with one patient so its reuse must be avoided. Based on information declared in the label, only a minority of PPE can be washable and manufactured for multiple use. 2. Disposable PPE cannot be properly washed or sanitized. 3. Workers using PPE should avoid touching contaminated surfaces and, if it is not possible, clean environmental surfaces or body sites should be touched before. 4. All PPE has to be kept in disposable state and the damaged or contaminated equipment has to be replace immediately. 5. PPE has not be shared with other healthcare workers and reusing PPE could increase the risk of contracting infections. 6. PPE should be select by considering anticipated exposure, durability and appropriateness and comfort with respect to the worker.

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2. Prevention of Needlestick /Sharp Injuries The Centers of Disease and Control Prevention (CDC) of Atlanta strongly recommend sharp and needlestick injury prevention as a major health priority. This last statement is supported by the consideration that every day more than 1,000 needlesticks and other sharpsrelated injuries are sustained by US HCWs [37]. However, these data may underestimate the real occupational risk since several surveys indicate that up to 50% of HCWs do not report their percutaneous injuries [33, 38, 39]. Generally, injuries occur during use of a device on patients (41%) or before disposal of a sharp device (40%) and, rarely, during or after disposal (15%) [40]. During all activities, a low compliance with guidelines on safe handling and disposal of sharps has been documented to increase the incidence of needlestick injury [41, 42]. The Health Protection Agency estimates that between 1997 and 2004, 38% of all percutaneous exposures could have been prevented by adherence to procedure for safe handling of sharps and clinical waste [43]. Although several studies observed HCW compliance with handling and disposal of sharps and good adherence was commonly reported [44, 45], some unsafe practices have been identified. Re-sheathing has been strongly discouraged for many years [1] but in 2004 Bennett and Mansell found that 7% and 11% of community nurses admitted re-sheathing disposable Vacuitaners and needles following injection, respectively [45]. Disposal of sharps was also associated with 15% to 48% of all sharps-related exposures [46] of which a large majority is caused by overfilled sharps boxes [45].

Concluding, an unacceptably suboptimal compliance with PPE and procedure for safe handling of sharps is worldwide reported, although a certain variability exists in different geographic areas [47]. In particular, full compliance rates below 5% were observed in some Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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UK and US healthcare settings [33, 48] and up to 60% of HCWs were uncompliant in Danish [49] and Canadian studies [50]. It is also evident that HCWs are selective in their adherence to different types of PPE and respiratory protection devices showed generally the lowest compliance [31]. The main reasons for poor compliance and authors who reported observation are listed in Table 1. Table 1. Reasons for noncompliance with personal protective equipment among healthcare workers Author

Country

Year

Perception that the patients are low risk

- Cutter et al. - Ferguson et al.

- UK - USA

- 2004 - 2004

Forgetfulness

- Madan et al.

- USA

- 2002

- Ferguson et al.

- USA

- 2004

- Ji et al. - Sax et al.

- China - Switzerland

- 2005 - 2005

- Tait et al.

- USA

- 2000

- Madan et al.

- USA

- 2002

- Sax et al.

- Switzerland

- 2005

- Tait et al.

- USA

- 2000

- Ferguson

- USA

- 2004

Lack of knowledge or training

- Bennet et al.

- UK

- 2004

Lack of faith in the efficacy of equipment

- Ferguson et al.

- USA

- 2004

Fear concerning loss of dexterity

- Nelsing et al.

- Denmark

- 1997

- Stein et al. - Bennet et al. - Cutter et al. - Ferguson et al.

- UK - UK - UK - USA

- 2003 - 2004 - 2004 - 2004

- Nelsing et al. - Bennet et al. - Ferguson

- Denmark - UK - USA

- 1997 - 2004 - 2004

Time factors

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No anticipated exposure

Lack of availability of PPE

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1. Hand Hygiene Hospital-acquired infections are a major threat to patients and place a great burden on healthcare services. Since healthcare workers‘ hands represent the principal route of transmission of pathogens in health care setting, hand hygiene compliance is of crucial importance to prevent nosocomial infections and has been identified as a health policy priority [51]. Hand hygiene was one of the first medical measures assessed with epidemiologic methods [52]. Failure to wash hands between patients and after glove use potentially jeopardizes the health of both HCWs and their patients through the spread of microorganisms as HIV and many other pathogens contained in biological samples. Despite being widely accepted as one of the most important means of controlling the spread of these infections, hand hygiene compliance rates in healthcare setting remain low. Factors as the professional role, the contagious status of the patient and how busy a unit is, have been associated with low compliance rates [53]. An observational study conducted in Belgium from Noritomi et al [53], demonstrated that doctors had better compliance rates than did nurses and that male HCWs were more compliant than female staff. On the contrary, another study [54] showed that the female staff washed their hands more often than male staff although this difference only persisted among physicians and wardpersons. Moreover, Noritomi et al [53] observed that procedures associated with patients under enteric isolation were correlated with a higher rate of compliance suggesting that conscious perception of the importance of hand disinfection may play a role in these instances; probably, there is a tendency for HCWs to disinfect the hands more often after a dirty contact than after a clean contact, as shown by a study [55] carried out to investigate how often healthcare workers apply antiseptic handrubs after different activities ranked according to the risk of hand contamination (Fulkerson Scale, Table 2). This study reported that after contact with faeces (rank 12), antiseptic handrub was used in 97.3% of the observations, while the rate of handrub use after direct or indirect contact with infectious material (ranks 13 to 15) ranged from 78.6% to 85.1%. It seems that contact with urine or faeces is judged to be of higher risk than contact with infected patients [55]. In general, many studies [56, 57, 58] find much higher rates of hand hygiene after patient contact than before patient contact; this datum shows that hand hygiene is perhaps influenced more by the inherent desire to clean oneself when feeling dirty than by an interest in protecting the patient. In other observational studies conducted in hospitals, HCWs cleaned their hands on average from 5 to as many as 42 times per shift and 1.7-15.2 times per hour [51]. This finding provides an indication that the number of opportunities for hand hygiene per HCW varies markedly between hospital wards; nurses in paediatric wards, for example, had an average of 8 opportunities for hand hygiene per hour of patient care, compared with an average of 30 for nurses in Intensive Care Units [51]. There are many different reasons why healthcare workers disinfect their hands much less often than necessary. These include :  

Insufficient knowledge of the clinical situations in which the patient clearly benefits Lack of products or dispensers: unavailability of the disinfecting handrub right where it is needed

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E. Amodio, N. Romano and M. Antonella Di Benedetto

38    

Lack of time: hand disinfection is frequently not carried out because of increasing pressure of work Cutaneous irritation: skin problems with use (e.g. dryness) Occurrence of emergent situations Failure of high-ranking medical staff to set an example: junior HCWs will think that hand disinfection cannot be very important if senior medical staff dispense with it.

Compliance could be improved by knowledge of the principal clinical circumstances in which hand disinfection is indispensable [59]. Table 2. Fulkerson Scale Ranking Contacts of Healthcare Personnel from clean to dirty* Rank

1 2 3 4

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5 6 7 8 9 10 11 12 13 14 15

Contact with

Sterile or autoclaved materials Thoroughly cleaned or washed materials Materials not necessarily cleaned but free from patient contact (e.g., paper) Objects contacted by patients either infrequently or not expected to be contaminated (e.g., patient furniture) Objects intimately associated with patients, but not known to be contaminated (e.g., patient gowns, linens, dishes, and bedside rails) Patients but minimal and limited (e.g., shaking hands and taking pulses) Objects in contact with patient secretions Patient secretions or mouth, nose, or genitoanal area Material contaminated by patient urine Patient urine Materials contaminated with faeces Faeces Materials contaminated with secretions or excretions from infected sites (e.g., wounds or tracheotomy)

* Data from Wendt et al, 2004 [55].

2.

Cleaning of Surfaces Maintaining a clean environment is a social obligation of hospitals because some microorganisms can contaminate and survive in the inanimate environment (Table 3) [60]; the organisms that cause infection are invisible to the naked eye and their existence is not necessarily associated with the presence of visual dirt. The most relevant nosocomial pathogens can persist on dry inanimate surfaces for months; in addition to the duration of persistence, some studies have also identified factors influencing persistence. For example, a low temperature, such as 4° C or 6° C, was associated with longer persistence for most bacteria, fungi and viruses [61]. Environmental cleaning is

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an important part of infection-control for influenza, parainfluenza, enteric viruses, severe acute respiratory syndrome (SARS)-associated coronavirus, hepatitis B virus (HBV) and hepatitis C virus (HCV) [62]. Table 3. Persistence of clinically relevant microorganisms on contaminated environmental surfaces* Microorganism

Time of persistence (range)

HBV HCV HIV HAV Candida albicans Haemophilus influenzae Staphylococcus aureus, including MRSA

> 7 days * 16 h - 63 days ** > 7 days * 2 hours- 2 months * 1 – 120 days * 12 days * 7 days- 7 months *

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* Data from Kramer et al. 2006 ** Data from Kamili et al. 2007 ; Paintsl et al 2010

The use of molecular epidemiology has helped to enhance understanding of the role of the environment in nosocomial infections by confirming that isolates in the environment either are the same as isolates recovered from patients [61]. During an influenza pandemic, the virus transmission may be reduced by the adoption of appropriate hygiene measures, including cleaning of surfaces likely to be contaminated by virus; Greatorex et al. [63] showed that 1% household bleach, which equates to 0.05% sodium hypochlorite, are sufficient for the inactivation of human influenza viruses. It has been documented that influenza A viruses can survive for a prolonged period on different types of surfaces once they are present in the environment. Indeed, contamination of hands after contact with an influenza virus-contaminated surface has been demonstrated and infectious influenza virus was isolated from hands after contact with a porous surface contaminated for 15 min, as well as after contact with a nonporous surface contaminated for 24 h [64]. A study conducted in Switzerland [65] showed that infectious influenza virus can survive for several days in banknotes; this requires a relatively large inoculum and the presence of a protective matrix, such as respiratory mucus. Indeed, for any environmental contamination to be relevant , the virus should not only remain infectious but also persist at a sufficient concentration to enable it to reach the respiratory tract via finger contamination. Rhinovirus is the most common respiratory virus known to be easily transmitted by this route [66]. Blood from HBV infected persons with active viral replication may have high levels of virus, and small, visually undetectable inocula may be highly infective; HBV is a virus known to be stable in the environment and that, compared with HCV, generally circulates in the blood of infected persons at concentrations that are 2–4 log higher. HBV may survive for up to 7 days in relative humidity of 42% [60, 67]. Outbreaks of hepatitis B that have involved

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E. Amodio, N. Romano and M. Antonella Di Benedetto

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fomites have been traced to contaminated electroencephalographic electrodes and to lancets used in the monitoring of glucose levels [68]. Kamili et al [62] showed that HCV in plasma can survive drying and environmental exposure to room temperature for at least 16 hours but a recent study [69] showed that HCV might still be transmissible via syringes long after their first use until to 63 days. The investigators looked at 2 types of syringes and blood volumes: a low–volume insulin syringe with a permanently attached needle filled with 2 µl of blood, and a higher-volume tuberculin syringe with a detachable needle filled with 32 µl of blood. The results showed that survival of infectious HCV is dependent on syringe type and size, with detachable-needle syringes and high-volume syringes being more likely to transmit the virus. Comparing with HIV, they found that HCV and HIV in low-volume syringes show a similar time course, but HCV appears to survive longer than HIV in high-volume tuberculin syringes. These findings support the results of epidemiologic studies that implicate crosscontamination from inanimate surfaces, objects or devices in HCV transmission [70] in health care settings and among injection drug users [71, 72].

3. Education and Training of Workers Healthcare workers (nurses, surgeons, midwifes, housekeepers, physicians, laboratory workers, dentists, etc.) are at risk for blood-borne infections at their workplace; reduction of occupational exposures to blood and body fluids remains an important challenge to healthcare professionals. The CDC recommended the routine use of SP over a decade ago but numerous studies indicate that HCWs fail to comply with the CDC guidelines and that the level of work experience has not been correlated with compliance rates [59,73]. In a study of HCWs in an emergency department, Meengs et al. [74] noted that the number of years of clinical experience was not significantly related to hand-washing frequency. This result is of considerable importance, as it suggests that work experience, even in a teaching hospital, does not influence an individual‘s hand hygiene behaviour over time. In addition, it suggests a cycle of incorrect practice in the working environment. Some studies [75] have showed that HCWs sharing washing facilities with a senior staff member or higher-ranking coworker who does not wash his or her hands are significantly less likely to wash their own hands, thus perpetuating poor compliance. Senior members of medical staff must recognize that they have to set an example and act accordingly. Therefore, the most critical point for the biosafety is not sophisticated devices or facilities, but health education of HCWs; as the outcome of an infection can be fatal, the phenomenon deserves serious attention. Multifaced approaches which combine education with written material, reminders and continued feedback of performance can have an important effect on SP compliance [76]. There are four major components to healthcare worker safety programs: first are training and administrative controls, like isolation policies and procedures for recognizing patients with a communicable disease before they expose workers; second are engineering controls like negative pressure rooms for patients with airborne diseases such as Tuberculosis (TB); third are work practice controls such as not recapping needles; fourth is proper use of personal protective equipment (PPE). While PPE is last in the hierarchy of prevention, it is very important for protecting healthcare workers and others workers (policeman, hairdresser, barber, podologist, tattooing worker, etc.) potentially exposed to blood-borne infections from disease transmission.

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Indeed, improper use of gloves could result in failure to prevent the occupational infections because gloves can become carriers of pathogens through contact of contaminated surfaces. Studies have shown that microorganisms including Escherichia coli, Staphylococcus aureus and viruses could be transferred from infected sources to gloves, making gloves a potential source of microbial contamination [77, 78]. More recently, a cross-sectional survey [79] was conducted in another setting of workers (105 hairdressers of Palermo city) to evaluate knowledge, attitudes and behaviours towards occupational risk of HIV, HBV and HCV infections. This study highlighted the need to produce appropriate educational materials for salons and to establish obligatory refresher courses. It showed unsafe practices such as not wearing gloves after an accidental cut on customers and reusing the same blades and gloves on multiple clients. Educational campaign and feedback on adequacy of discharge cleaning were found to be effective in improving environmental cleaning [80]. Indeed, increasing the volume of disinfectant applied to environmental surfaces, providing education for Environmental Services Staff, and instituting feedback with a black-light marker improved cleaning and reduced the frequency of MRSA and VRE contamination. In an early study [81], the knowledge and preventive practices toward the risk of infection with HIV, HBV and HCV were evaluated in a sample of 254 dentists and odontostomatologies in Palermo (South Italy). The results showed a significant correlation between better knowledge and safer practice. Also surgical personnel working in four specialties (cardiothoracic, general, gynaecologic and orthopaedic) in the operating room improved their compliance with SP and at 1- and 2years post-implementation of an educational intervention [82]. The findings showed that the wearing of double gloves and protective eyewear by surgical personnel increased following the educational intervention, whereas the incidence of documented blood and body fluid exposures decreased. Therefore, education programs for healthcare personnel, particularly those in outpatient settings, should include review of aseptic practices for injection and infusion procedures, such as always using a new needle and syringe every time fluid is withdrawn from a multidose vial and restricting medications and intravenous solutions to single patients [69]. A climate of prevention must be established in health care settings to increase the consistent use of SP by HCWs both seniors and juniors; senior staff should first recognize that the risk of transmission of infectious microorganisms can be high and should educate juniors to minimize the risk. In addition, each hospital should ensure administrative support, strong initial training, continuing education, regular encouragement and monitoring of SP compliance.

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CDC-Universal Precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in healthcare settings. – MMWR, 1988; 37: (I) 377-388

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[11]

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E. Amodio, N. Romano and M. Antonella Di Benedetto West KH, Cohen ML – Standard Precautions- a new approach to reducing infection transmission in the hospital setting. J Intraven Nurs, 1997 Nov-Dec: 20 (6 Suppl.): S710 Garner JS. Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol, 1996; 17: 5380 Beltrami EM, Williams IT, Shapiro CN, Chamberland ME. – Risk and management of blood-borne infections in health care workers. Clin Microbiol Rev, 2000; 13: 385-407 Di Benedetto M.A., Vitale F., Cannova L., Cabibi D. – Rischio biologico da virus ematici in operatori sanitari. Osservatorio Epidemiologico, Notiziario 2003. www.doesicilia.it Pruss-Ustun A, Rapiti E, Hutin Y: Estimation of the global burden of disease attributable to contaminated sharps injuries among health-care workers. Am J Ind Med. 2005, 48(6):482-490. Cleveland JL, Siew C, Lockwood SA, Gruninger SE, Gooch BF, Shapiro CN. Hepatitis B vaccination and infection among US dentists, 1983-1992. J Am Dental Ass, 1996; 127: 1385-1392. Bell DM- Occupational risk of human immunodeficiency virus infection in healthcare workers : An overview. Am J Med, 1997; 102 (5B): 9-15. Kermode M, Holmes W, Langkham B, Thomas MS, Gifford S. HIV-related knowledge, attitudes and risk perception amongst nurses, doctors and other healthcare workers in rural India. Indian J Med Res, 2005; 122(3): 258-264. Kampf G, Kramer A.-Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs. Clin Microb Rev, 2004; 17 (4): 863-893 Mendoza C, Barrientos C, Vasquez R, Panizza V. Exposiciòn laboral a sangre y fluidos corporals. Experiencia en un hospital pediatrico. Revista Chilena de Infectologìa, 2001; 18 (1) :28-34. Erasmus V, Brouwer W, van Beeck EF, Oenema A, Daha TJ, Richardus JH, Vos MC, Brug J. – A qualitative exploration of reasons for poor hand hygiene among hospital workers: lack of positive role models and of convincing evidence that hand hygiene prevents cross-infection. Infect Control Hosp Epidemiol, 2009; 30 : 415-419. Brevidelli MM, Cianciarullo TI - Nìveis de adesão às precaucões-padrão entre profissionais medicos e de enfermagem de um hospital universitàrio. Braz J Nurs, 2006 (Online). Disponìvel em: http:// www.uff.br/objnursing/viewarticle. Lopes ACS, Oliveira AC, Silva JT, Paiva MHRS. - Adesão às precaucões-padrão pela equipe do atendimento prè-hospitalar mòvel de Belo Horizonte, Minas Gerais, Brasil. Cad Saude Publica, 2008; 24(6): 1387-1396. Brevidelli MM, Cianciarullo TI. Psychosocial and organizational factors relating to adherence to standard precautions. Rev Saùde Pùblica, 2009; 43(6). Centers for Disease Control and Prevention. 2007. Guideline for isolation precautions: preventing transmission of infectious agents in healthcare setting. http:// www.cdc.gov/ncidod/dhqp/gl_isolation_standard.html Pittet D, Dharan S, Touveneau S, Sauvan V, Perneger T V. Bacterial contamination of the hands of hospital staff during routine patient care. Arch. Int.Med. 1999; 159: 821826.

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[18] Pittet D, Boyce JM. Hand hygiene and patient care: pursuing the Semmelweis legacy. Lancet Infect Dis. 2001; 9-20. [19] Kralj N, Beie M, Hofmann F. Surgical gloves - how well do they protect against infections? Gesundheitswesen, 1999; 61:398-403. [20] Tenorio AR, Badri SM, Hota B, Matushek M, Hayden MK, Trenholme GM, Weinstein RA. Effectiveness of gloves in the prevention of hand carriage of vancomycin-resistant Enterococcus species by health care workers after patient care. Clin. Infect. Dis., 2001; 32: 826-829 [21] Girou E. Prevention of nosocomial infections in acute respiratory failure patients. Eur Respir J Suppl. 2003 Aug; 42:72s-76s. [22] Ray AJ, Hoyen CK, Taub TF, Eckstein EC, Donskey CJ. Nosocomial transmission of vancomycin-resistant enterococco from surfaces. J Am Med Assoc. 2002;287:14001401. [23] Naing L, Nordin R, Musa R.The prevalence of, and factors related to, compliance with glove utilization among nurses in Hospital Universiti Sains Malaysia. Southeast Asian J Trop Med Public HealthJi G, Yin H, Chen Y. Prevalence of and risk factors for noncompliance with glove utilization and hand hygiene among obstetrics and gynaecology workers in rural China. Journal of Hospital Infection ,2005; 59:235–241. [25] Kuzu N, Ozer F, Aydemir S, Yalcin AN & Zencir M. Compliance with hand hygiene and glove use in an university-affiliated hospital. Infection Control and Hospital Epidemiology, 2005; 26: 312–315. [26] Golan, Y, Doron S, Griffith J, El Gamal H, Tanios M, Blunt K, Barefoot L, Bloom J, Gamson K, Snydman LK, Hansjosten K, Elnekave E, Nasraway SA & Snydman DR.The impact of gown-use requirement on hand hygiene compliance. Clinical Infectious Disease, 2006; 42: 370–376 [27] Puzniak LA, Gillespie KN, Leet T, Kollef M, Mundy LM. A cost-benefit analysis of gown use in controlling vancomycin-resistant Enterococcus transmission: is it worth the price? Infect Control Hosp EpidemiolSrinivasan A, Song X, Ross T, Merz W, Brower R, Perl TM. A prospective study to determine whether cover gowns in addition to gloves decrease nosocomial transmission of vancomycin-resistant enterococci in an intensive care unit. Infect Control Hosp Epidemiol. 2002; 23: 424-428 [29] Slaughter S, Hayden MK, Nathan C, Hu TC, Rice T, Van Voorhis J, Matushek M, Franklin C, Weinstein RA. A comparison of the effect of universal use of gloves and gown with that of glove use alone on acquisition of vancomycin-resistant enterococci in a medical intensive care unit. Ann Intern Med 1996; 125:448-456 [30] Manian FA, Ponzillo JJ. Compliance with routine use of gowns by healthcare workers (HCWs) and non-HCW visitors on entry into the rooms of patients under contact precautions. Infect Control Hosp EpidemiolGammon J, Morgan-Samuel H, Gould D. A review of the evidence for suboptimal compliance of healthcare practitioners to standard/universal infection control precautions. J Clin NursMadan AK, Raafat A, Hunt JP, Rentz D, Wahle MJ, Flint LM. Barrier precautions in trauma: is knowledge enough? J Trauma. 2002 Mar;52(3):540-543 [33] Cutter J, Jordan S. Uptake of guidelines to avoid and report exposure to blood and body fluids. Journal of Advanced Nursing 2004; 46, 441–452

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[34] National Institute for Occupational Safety and Health (NIOSH). Eye Protection for Infection Control. September 2004. [35] Evanoff B, Kim L, Mutha S, Jeffe D, Haase C, Andreck D & Fraser V.Compliance with universal precautions among emergency department personnel caring for trauma patients. Annals of Emergency Medicine, 1999; 33: 160–165. [36] Osborne S. Influences on compliance with standard precautions among operating room nurses. American Journal of Infection Control, 2003 ; 31: 415–423. [37] Panlilio AL, Orelien JG, Srivastava PU, Jagger J, Cohn RD, Carco DM, the NaSH Surveillance Group; the EPINet Data Sharing Network. Estimate of the annual number of percutaneous injuries among hospital-based healthcare workers in the United States, 1997-1998. Infect Control Hosp Epidemiol, 2004; 25(7):556- 562. [38] Perry J, Robinson ES, Jagger J. Needle-stick and sharps-safety survey. Nursing, 2004; 34(4):43-7. [39] Sohn S, Eagan J, Sepkowitz KA. Safety-engineered device implementation: does it introduce bias in percutaneous injury reporting? Infect Control Hosp Epidemiol. 2004; 25(7):543-7 [40] http://www.cdc.gov/sharpssafety/ [41] Gould D. (1994) Sharps handling and disposal: a study. Nursing Standard. 8, 25–28. [42] Weltman AC, Short LJ, Mendelson MH, Lilienfeld DE e Rodriguez M. Disposalrelated sharps injuries at a New York City teaching hospital. Infection Control and Hospital Epidemiology 1995; 16, 268– 274 [43] Health protection agency centre for infections and collaborators. Occupational transmission of HIV. Summary of published reports. March 2005 edition. [44] Chan R, Molassiotis A, Chan E, Chan V, Ho B, Lai CY, Lam P, Shit F, Yiu I. Nurses' knowledge of and compliance with universal precautions in an acute care hospital. Int J Nurs StudBennett G, Mansell I. Universal precautions: a survey of community nurses' experience and practice. J Clin NursPerry J, Parker G, Jagger J. Percutaneous injuries in home healthcare set setting. Home Healthc Nurse 2001; 19(6): 342-347. [47] McCoy KD, Beekmann SE, Ferguson KJ, Vaughn TE, Toner JC, Woolson RF & Doebbeling BN. Monitoring adherence to standard precautions. American Journal of Infection Control, 2001 ; 29: 24–31. [48] Madan AK, Raafat A, Hunt JP, Rentz D, Wahle MJ, Flint LM. Barrier precautions in trauma: is knowledge enough? J Trauma. 2002 ; Mar;52(3): 540-543. [49] Nelsing S, Neilsen TH, Nielsen JO. Non-compliance with universal precautions and the associated risk of muco-cutaneous blood exposure among Danish physicians. Infection Control and Hospital Epidemiology, 1997; 18. 692–698. [50] Godin G, Naccache H, Morel S, Ebacher MF. Determinants of nurses‘ adherence to universal precautions for venepuncture. American Journal of Infection Control, 2000; 28, 359–364. [51] WHO: WHO guidelines on hand hygiene in health care. First global patient safety challenge – clean care is safer care. Geneva: WHO; 2009. [52] Semmelweis IP. Die Atiologie, der Begriff und die Prophylaxis des kindbettfiebers. Pest, Hungary: C.A. Hartleben; 1861.

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[53] Noritomi DT, Chierego M., Byl B., Menestrina N., Carollo T., Struelens M., Vincent JL. Is compliance with hand disinfection in the intensive care unit related to work experience? Infect Control Hosp Epidemiol. 2007; 28 : 362-364. [54] Van de MT, Bourke R., McLoughlin J, Nonu M, Reis M. Gender influences handwashing rates in the critical care unit. Am J Infect Control, 2001; 29: 395-399. [55] Wendt C, Knautz D, von Baum H. Differences in hand hygiene behavior related to the contamination risk of healthcare activities in different groups of healthcare workers. Infect Control Hosp Epidemiol. 2004; 25 : 203-206. [56] O‘Boyle CA, Henly SJ, Larson E. Understanding adherence to hand hygiene recommendations: the theory of planned behaviour. Am J Infect Control 2001; 29: 352360. [57] O‘Boyle CA, Henly SJ, Duckett LJ. Nurses‘ motivation to wash their hands: a standardized measurement approach. Appl Nurs Res. 2001; 14 : 136-145. [58] Aragon D, Sole ML, Brown S. Outcomes o fan infection prevention project focusing on hand hygiene and isolation practices. AACN Clin Issues, 2005; 16 : 121-132. [59] Kampf G, Löffler H, Gastmeier P. Hand hygiene for the prevention of nosocomial infections. Dtsch Arztebl Int. 2009; 106 (40) 649-655. [60] Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infectious Diseases, 2006; 6 : 130-137. [61] Bala Hota. Contamination, disinfection, and cross-colonization: are hospital surfaces reservoirs for nosocomial infection?. Clin Infect Dis. 2004; 39: 1182-1189. [62] Kamili S, Krawczynski K, McCaustland K, Xiaofang L, Alter MJ. Infectivity of hepatitis C virus in plasma after drying and storing at room temperature. Infect Control Hosp Epidemiol. 2007; 28: 519-524. [63] Greatorex JS, Page RF, Curran MD, Digard P.,Enstone JE, Wreghitt T, Powell PP, Sexton DW., Vivancos R.,Nguyen-VT JS. Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1. PLoS One. 2010; 5(2): e8987. Published online 2010 February 1. doi: 10.1371/journal.pone. 0008987. [64] Bean B, B M Moore, Sterner B, Peterson L R, Gerding D N, Balfour H H . 1982. Survival of influenza-viruses on environmental surfaces. J Infect Dis. 146: 47-51. [65] Thomas Y, Vogel G, Wunderli W, Suter P, Witschi M, Koch D, Tapparel C, Kaiser L. 2008. Survival of influenza virus on banknotes. Applied and Environmental Microbiology. 74 : 3002-3007. [66] Hendley J O, R P Wenzel, J M Gwaltney. 1973. Transmission of rhinovirus colds by self-inoculation. Engl J Med. 288 : 1361-1364. [67] Zaidi M., Wenzel RP. Disinfection, sterilization, and control of hospital waste. In : Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious disease. 5th edition. Philadelphia: Churcill Livingstone, 2000 :3000-3002 [68] Hepatitis B outbreak investigation team. An outbreak of hepatitis B associated with reusable subdermal electroencephalogram electrodes. CMAJ, 2000; 162: 1127-1131. [69] Paintsl E, He E, Peters C, Lindenbach B, Heimer R. Survival of HCV in syringes: implication for HCV transmission among injection drug users. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 168, 2010.

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[70] Centers for Diseaes Control and Prevention. Transmission of hepatitis B and C viruses in outpatient settings – New York, Oklahoma, and Nebraska, 2000-2002. MMWR, 2003; 52: 901-906. [71] Hagan H, Thiede H, Weiss NS, Hopkins SG, Duchin JS, Alexander ER. Sharing of drug preparation equipment as a risk factor for hepatitis C. Am J Public Health, 2001; 91 : 42-46. [72] Hahn JA, Page-Shafer K, Lum PJ, Bourgois P, Stein E, Evans JL, Busch MP, Tobler LH, Phelps B, Moss AR. Hepatitis C virus seroconversion among young injection drug users: relationships and risks. J Infect Dis. 2002; 186 : 1558-1564. [73] Akduman D, Kim LE, Parks RL, L‘Ecuyer PB, Mutha S, Jeffe DB, Evanoff BA, Fraser VJ. Use of personal protective equipment and operating room behaviors in four surgical subspecialties: personal protective equipment and behaviors in surgery. Infect Control Hosp Epidemiol. 1999 Feb; 20(2): 110-114. [74] Meengs MR, Giles BK, Chisholm CD, Cordell WH, Nelson DR. Hand washing frequency in an emergency department. Ann Emerg Med. 1994; 23 : 1307-1312. [75] Lankford MG, Zembower TR, Trick WE, Hacek DM, Noskin GA, Peterson LR. Influence of role models and hospital design on hand hygiene of healthcare workers. Emerg Infect Dis. 2003; 9 : 217-223. [76] Naikoba S, Hayward A. The effectiveness of interventions aimed at increasing handwashing in healthcareworkers – a systematic review. J Hosp Infect. 2001 Mar; 47 (3) : 173-180. [77] Montville R, Chen Y, Schaffner DW. Glove barriers to bacterial cross-contamination between hands to food. J Food Prot. 2001; 64: 845- 849. [78] Majioie IML, von Blomberg BME, Bruynzeel DP. Development of hand eczema in junior haidressers an 8-year follow-up study. Contact Dermat. 199; 34 : 243-247. [79] Amodio E, Di Benedetto MA, Gennaro L, Maida CM, Romano N. Knowledge, attitudes and risk of HIV, HBV and HCV infections in hairdressers of Palermo city (South Italy). Eur J Public Health 2009 Nov 5. [80] Goodman ER, Platt R, Bass R, Onderdonk AB, Yokoe DS, Huang SS. Impact o fan environmental clearing intervention on the presence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci on surfaces in intensive care unit rooms. Infect Control Hosp Epidemiol. 2008; 29 (7) : 593-599. [81] Vitale F, Di Benedetto MA, Casuccio A, Firenze A, Calandra G, Ballarò F, Romano N. Influenza dei percorsi formativi sulle conoscenze di infezioni da HIV, HBV e HCV nella pratica odontoiatrica. Ann Ig. 2005; 17: 185-196. [82] Lynn EK, Jeffe DB, Evanoff BA, Mutha S, Freeman B, Fraser VJ. Improbe compliance with universal precautions in the operating room following an educational intervention. Infect Control Hosp Epidemiol. 2001; 22: 522-524.

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Chapter 3

LEARNING AND TEACHING OF COMPUTER PROGRAMMING: PAST AND FUTURE Wilfred W.F. Lau* and Allan H.K. Yuen Faculty of Education, The University of Hong Kong, Pokfulam Road, Hong Kong

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ABSTRACT Research into computer science education has spanned a broad range of topics. Learning to program is notably an area that has received much attention over the years since virtually every computer science program requires the mastery of programming skills and knowledge. This chapter aims to review four significant research strands of learning and teaching of computer programming, namely cognitive consequences and transfer effects of learning of computer programming, differences between novices and experts, programming knowledge and strategies, and program comprehension and composition. It first surveys some important studies performed in these strands in the past. Then for each strand, it recommends some literature-based research directions for future studies. While these recommendations still need further empirical support, such a review provides valuable avenues for researchers and practitioners alike towards advancement in their professions.

INTRODUCTION As a core component in computer science education, learning to program poses a lot of difficulties to novices (Johnson, 1990; Sleeman, Putnam, Baxter, & Kuspa, 1988; Soloway, Bonar, & Ehrlich, 1983; Spohrer & Soloway, 1986; Spohrer, Soloway, & Pope, 1985). Dijkstra (1989) described programming as ―radical novelty‖ in which our usual strategy of metaphors and analogies simply does not apply. Pea (1986) identified three types of bugs *

Corresponding author. Tel: 852 28592540; fax: 852 25406360. E-mail address: [email protected].

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while studying high school students learning of computer programming. They are parallelism bugs, intentionality bugs, and egocentrism bugs. These conceptual bugs are rooted in a ―superbug‖ that ―there is a hidden mind somewhere in the programming language that has intelligent interpretive powers‖ (pp. 32-33). Ben-Ari (1998) suggested that students lack a viable mental model to learn computer programming and teachers should therefore teach such a model explicitly. Jenkins (2002) argued that programming is a complicated task, which requires the mastery of a number of skills such as problem solving, abstraction, mathematical logic, mechanic, testing and debugging, and life skills. As a novice programmer, he or she simply lacks these skills. Jenkins also noted that these skills form a hierarchy that makes students learn the lower-level skills first before going upwards. That is to say, students will concentrate on the syntax of the language at the expense of learning the higher-level skills like data-structure and algorithms. This hinders students‘ deep understanding of programming and students are unlikely to be able to write a program in a structured manner. Deek (1999) summarised three kinds of difficulties faced by students when learning to program: (1) deficiencies in problem solving strategies and tactical knowledge; (2) ineffective pedagogy of programming instruction; and (3) misconceptions about syntax, semantics, and pragmatics. According to Deek, students simply lack programming skills, knowledge, and strategies to write a program. Also, teaching tends to focus on the implementation of program at the expense of design. It is evident that most textbooks devote themselves mostly to teaching of programming language syntax. Finally, students do not have clear ideas of what programming and programming language are all about. To sum up, it can be said that difficulties in learning to program stem from three major areas: (1) lack of programming skills, knowledge, and strategies; (2) lack of mental models of computer, programming, and programming language; and (3) ineffective programming instruction. Perhaps it is due to these difficulties that research into learning and teaching of computer programming has drawn much attention and spanned a broad range of topics ever since the popularity of computers in schools in the 1980s. This chapter aims to review research strands of learning and teaching of computer programming in the past and attempts to predict future trends of research in these strands drawing on pertinent literature.

RESEARCH STRANDS OF LEARNING AND TEACHING OF COMPUTER PROGRAMMING Research into learning and teaching of computer programming has been done since the 1970s. This research area was mainly driven by advances in computer technology as well as the introduction of computer studies/science as an academic discipline into schools or universities. Broadly speaking, depending on the perspectives of the researchers, the focus of research can be divided into two main categories: (1) programming as a cognitive process and (2) programming as a learning process. In the former case, considerable efforts are paid to the study of cognitive factors influencing learning and teaching of computer programming. For example, what is the nature of programming expertise? What are the difficulties in learning to program? In the latter case, attentions are drawn to the pedagogical issue of learning to program including approaches and tools of teaching of computer programming, teaching of a

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particular construct, and debugging. In an influential article, Robins, Rountree, and Rountree (2003) made a review on learning and teaching of computer programming. Specifically, the researchers identified several significant strands in research on computer programming. In the following sections, four research strands on learning and teaching of computer programming are identified and discussed with reference to their review. These strands are cognitive consequences and transfer effects of learning of computer programming, differences between novices and experts, programming knowledge and strategies, and program comprehension and composition.

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COGNITIVE CONSEQUENCES AND TRANSFER EFFECTS OF LEARNING OF COMPUTER PROGRAMMING During the 1980s, computers were introduced into schools and became part of the curriculum. Papert (1980) advocated a new kind of educational environment that encourages free contact between children and computers. Papert proclaimed that ―in teaching the computer how to think, children embark on an exploration about how they themselves think‖ (p. 19) and the result was that ―powerful intellectual skills are developed in the process‖ (p. 60). It is perhaps through this advocacy that two main research questions emerged in the 1980s: (1) What are the cognitive consequences on children of learning to program? and (2) Are these consequences transferable to other domains? In a study conducted by Linn and Dalbey (1985), over 500 students in 17 classes from 6 schools were examined for their chains of cognitive accomplishments from programming instruction. The chain has three main links: (1) single language features; (2) design skills; and (3) general problem-solving skills. Typical instruction was used in four schools whereas exemplary instruction, where design skills were explicitly emphasized, was used in the other two schools. The study also looked at other factors such as ability, computer access, and gender on programming performance. Among all the findings in this study, it was found that exemplary instruction moved students further along the chain of cognitive accomplishments and ability had no influence on programming performance provided that exemplary instruction was administered. It is clear from these findings that cognitive development in learning to program and performance is enhanced by explicit instruction. Palumbo and Reed (1991) commented on the deficiencies of previous research studies aimed at investigating the relationship between programming instruction and problem-solving skills. Palumbo and Reed identified five major categories of these deficiencies: (1) programming language/problem-solving studies not firmly grounded in the problem-solving theories; (2) quality, length, and intensity of the treatment presented; (3) appropriateness of the programming language selected and the method of instruction; (4) computer system as a whole and the extent to which the computer serves as an instructional medium; and (5) selection of an appropriate sample. Having considered these categories in their research design, Palumbo and Reed selected 22 students in a high school to participate in their study. Among these students, eleven were enrolled in a first-year programming course in BASIC while the others were enrolled in a computer literacy course in which only basic skills of computer operations were taught. The programming instruction lasted for 15 weeks and

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students‘ performance in programming, problem-solving skills, and computer anxiety was recorded in the 5th, 10th, and 15th week. It was found that the BASIC programming group performed significantly better than the computer literacy group in the 15-week period. Also, for the BASIC programming group, those who scored higher in the programming performance measures tended to score higher in the problem-solving measures too. In a similar study, Bernardo and Morris (1994) investigated the transfer effects of BASIC programming course on skills in mathematical modelling, procedural comprehension, and verbal problem solutions on three groups of high school students, namely BASIC programming group, computer literacy group, and nonexposure group. Although there were no significant differences in mathematical modelling and procedural reasoning among the groups, the BASIC programming group outperformed the two other groups in verbal problem solutions. This result reinforces the idea that exemplary programming instruction enhances problem-solving skills as advocated by Linn and Dalbey (1985). While the above studies focus on high school subjects, other studies attempt to establish similar results in colleges. Choi and Repman (1993) examined the effects of Pascal and FORTRAN programming on the problem-solving skills of college students. Their methodology was similar to that of Palumbo and Reed‘s (1991) study. However, Choi and Repman used three groups of students: (1) Pascal programming group (n = 18); (2) FORTRAN programming group (n = 19); and (3) control group (n = 21). Results revealed that while no significant difference in problem-solving skills was observed in the Pascal and FORTRAN programming groups, the two groups were significantly better at problem-solving skills compared with the control group. Also, programming performance correlated with problem-solving skills for both programming groups. Norris and Jackson (1992) studied the effects of programming instruction on critical thinking skills and mental alertness of freshman college students. All subjects enrolled in a one-semester course in BASIC programming. In terms of testing, they were divided into two groups. One group of 39 students took the Watson-Glaser test for assessing critical thinking skills such as inference, deduction, and interpretation (Watson & Glaser, 1980) and the another group of 33 students took the Thurstone test for assessing mental ability in quantitative and linguistic reasoning (Thurstone & Thurstone, 1986). A pre-test and post-test of both tests were administered to the students at the beginning and the end of the semester respectively. For both tests, students showed a significant increase in scores. The findings in general are consistent with that obtained for high school subjects. Regarding the transfer effects of learning of programming, Kurland, Pea, Clement, and Mawby (1989) reported a one-year study of three groups of high school students learning of computer programming. The study addressed three issues: (1) Did programming advance students‘ mathematical and reasoning ability? (2) What cognitive skills predict success in programming? and (3) What understanding of programming did students obtain after two years of study? The first group, experimental group, was in their second year of programming. The second group, some-CP group, had taken one year of programming but had chosen not to continue. The third group, no-CP group, had no programming experience. A number of tests were administered to the three groups of students using a pre-test/post-test method. Results revealed that students only had basic understanding of programming even after two years of study. Also, only ―near‖ transfer of skills (algorithm design and analysis) was evident. ―Far‖ transfer of skills (procedural reasoning, mathematics ability, and

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comprehension) was not observed. This one-year study also showed evidence of transfer of programming instruction on problem-solving and critical thinking skills (Norris & Jackson, 1992).

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DIFFERENCES BETWEEN NOVICES AND EXPERTS One strand of research into learning and teaching of computer programming is to understand the differences between novices and experts. Research in this strand provides insights into the nature of programming expertise. It has been suggested that experts are different from novices in their ability to chunk meaningful and useful information from programs to facilitate program construction and comprehension. Shneiderman and Mayer (1979) performed a program recall study on a group of subjects containing novices and experts. When programs were presented in proper order, experts tended to perform better than novices. However, experts did poorly for shuffled programs. The interpretation is that experts were able to chunk related parts into internal semantic structures and retrieve them in proper program. On the other hand, novices tended to focus on the syntactic aspect of the program and thus performed equally poorly in both proper and shuffled programs. Further evidence of chunking by experts was provided by Soloway and Ehrlich (1984). In their study, Soloway and Ehrlich proposed the idea of programming plans (i.e. program segments that represent typical programming actions) and rules of programming discourse (i.e. rules that govern programming conventions). Soloway and Ehrlich claimed that experts use programming plans and discourse rules in programming. To test the hypothesis, subjects including novices and experts were presented with plan-like and unplan-like versions of programs. They were asked to fill in a missing line of a program. Results showed that experts did significantly better than novices in plan-like programs but were no different than novices for unplan-like programs. The differences between experts and novices lie not only in programming knowledge but also in the use of programming strategies. Pennington (1987a) examined the differences in comprehension strategies employed by two groups of programmers (cf. novices and experts). Programmers were classified by an initial comprehension test into two groups, the top quartile and the bottom quartile groups. The two groups were given further comprehension tasks of a program of moderate length. Results suggested that the top comprehenders used a crossreferencing strategy that alternated between the program and problem domains. On the other hand, the poorer comprehenders tended to use a single strategy, which either focused on the program or problem domain. Wiedenbeck, Fix, and Scholtz (1993) identified five abstract features of mental representation of computer programs of experts in the programming literature: hierarchical structure, explicit mapping between layers, foundation on recognition of recurring patterns, connection of program parts, and grounding in the program text. Empirical evidence supported the existence of these characteristics in experts‘ programs. Winslow (1996) concluded from various studies that novices lack a viable mental model of programming, are limited to superficial knowledge, use general problem-solving strategies instead of problem-dependent strategies, focus on control structures of programs, and adopt a line-by-line, bottom-up approach in programming. In contrast, experts have a variety of mental models and use them in an opportunistic way, possess deep knowledge that is

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hierarchical and multi-layered, use different problem-solving strategies dependent on the familiarity of the problems, focus on algorithms rather than syntax, and have better programming knowledge. Von Mayrhauser and Vans (1994) also summarised the characteristics of experts based on the works of Guindon (1990) and Vessey (1985). It was noted that ―Experts organize knowledge structures by functional characteristics of the domain in which they are experts. Knowledge possessed by novices is typically organized according to the program syntax‖ (p. 5), ―Experts have efficiently organized specialized schemas developed through experience… experts not only used general problem-solving strategies such as divide-and-conquer, but also more specialized design schemas‖ (pp. 5-6), and finally ―Experts are flexible in approaches to problem comprehension…Experts tend to generate a breadth-first view of the program and then refine hypotheses as more information becomes available‖ (p. 6).

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PROGRAMMING KNOWLEDGE AND PROGRAMMING STRATEGIES A lack of programming knowledge is one of the difficulties encountered by novices in learning to program. Computer science educators have long been interested in the nature of programming knowledge. Shneiderman and Mayer (1979) suggested that there are two distinct types of programming knowledge, syntactic knowledge and semantic knowledge. Syntactic knowledge refers to the details of how computation is implemented in a particular programming language such as assigning a value to a variable. Semantic knowledge, on the other hand, requires understanding of programming constructs and concepts that are independent of specific programming languages. Shneiderman and Mayer further added that while the acquisition of semantic knowledge is largely intellectually demanding, syntactic knowledge is learnt primarily by rote. Building on the work of Shneiderman and Mayer (1979), Bayman and Mayer (1988) argued that learning of a programming language (BASIC) involves the mastery of syntactic knowledge, conceptual knowledge, and strategic knowledge. According to Bayman and Mayer, syntactic knowledge refers to knowledge about the features and facts of the language such as the fact that a new line must begin with a number. Conceptual knowledge refers to a conceptual model of the system including the kinds of actions, the kinds of locations, and the kinds of objects that take part in a computer operation. Finally, strategic knowledge refers to the use of syntactic and conceptual knowledge to solve novel problems. Empirical evidence has supported the hypothesis that the provision of conceptual models enhances the development of conceptual and strategic knowledge, in particular for the low ability students. The results are in accordance with the chains of cognitive accomplishments by Linn and Dalbey (1985). McGill and Volet (1997), drawing on the research in educational computing and cognitive psychology, proposed a conceptual framework for analysing students‘ programming knowledge. In their framework, programming knowledge contains five interrelated but conceptually distinct categories: declarative-syntactic, declarative-conceptual, proceduralsyntactic, procedural-conceptual, and strategic/conditional. Declarative-syntactic knowledge refers to the knowledge of the facts about a particular programming language. Declarative-

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conceptual knowledge refers to understanding of actions that take place in a program without the ability to actually write a program. Procedural-syntactic knowledge refers to the ability to produce a syntactically correct program in a programming language without necessarily understanding its semantics. Procedural-conceptual knowledge refers to the ability to write as well as understand the program implemented in a programming language. Finally, strategic/conditional knowledge refers to the ability to use both syntactic and conceptual knowledge to develop programs to solve novel problems. These five categories of programming knowledge are established through an empirical study of two groups of students. The experimental group students (n = 28) were instructed with emphasis on the use of planning strategy for algorithmic development and programming through an interactive teaching approach involving modelling, coaching, and collaborative learning. The control group students (n = 28), although they were introduced to algorithm development in the lectures, were instructed in a traditional way in which they were given set exercises and occasional group explanations. A final examination, which was carefully designed to assess students‘ knowledge in these five categories, was administered to students at the end of the course. Results showed that the experimental group excelled in procedural-conceptual and strategic/conditional knowledge over the control group. On the other hand, declarativesyntactic and declarative-procedural knowledge, which were believed to be acquired through traditional instruction, turned out to be not significantly different between the two groups. Apart from programming knowledge, programming strategies also play an important role in various programming activities. Davies (1993) conducted a review of strategies employed in program comprehension (Brooks, 1977, 1983), program generation (Green, Bellamy, & Parker, 1987; Rist, 1989), and studies on difficulties for novices in using programming strategies (Perkins & Martin, 1986). The researcher further argued that various models of program generation strategies have described programming behaviour differently, often resulting in conflicting predictions of strategies adopted by programmers. For example, Rist (1989) made a clear prediction of the relationship between the order of program generation and expertise. In particular, Rist‘s model predicted that experts generate code in schema order while novices generate code by focal expansion. Also, the order of generation of plan is reflected in the order of generation of the final program text. However, Green et al. (1987) made no predictions concerning the relationship between generation order and expertise. In fact, as the model by Green et al. used working memory as temporal storage of program fragments and there is no reason to believe that experts have greater working memory than novices, it is expected that experts and novices should display similar generation strategies. Based on the models presented by Green et al. (1987) and Rist (1989), Davies (1991) developed an integrated framework for understanding programming behaviour in code generation. The model helps to examine the programming strategies employed by programmers of varying skill levels using different languages. Empirical results revealed that knowledge representation is a developmental process in which the development of programming expertise (especially when comparing intermediates and experts) is ―finetuned‖ to focal elements of plans. Meanwhile, features of the language notations only facilitate generation strategies at the beginning. As programming expertise increases, its role as a determinant of strategies diminishes. The implication of these results clearly contributes

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to our understanding of programming strategies in general and to the interaction between programming expertise and language features in particular in programming generation.

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PROGRAM COMPREHENSION AND PROGRAM COMPOSITION Program comprehension is a process in which programmers try to understand what a program does. Program composition, on the other hand, requires the production of a program based on some specifications. It is regarded as the reverse process of program comprehension. Both processes are important in software design and maintenance. For example, in order to perform debugging on a program, the functionality of the program must first be understood. A number of program comprehension models have been proposed over the years. Brooks (1983) presented a program comprehension model which claims to explain behavioural differences in program comprehensibility such as the effects of differences in tasks performed by the program on comprehension. According to Brooks, program comprehension involves a construction of mappings from the problem domain to the programming domain, possibly through several intermediate domains. To illustrate his idea, Brooks considered a cargo-routing problem. The problem domain involves cargoes as objects that have destinations that must be reached within time and cost constraints. Before the program is constructed, numbers must be assigned to various time and cost constraints and identifiers assigned to the cargoes and destinations. This creates a new domain in which the objects are numbers. An algorithm must be selected to perform the required computation and this leads to a new domain of mathematical objects like trees or arrays. As these mathematical objects are implemented as data structures and primitive operations in programming language, another domain is created. Finally, execution of the program results in a further domain where objects are contents of memory location and operations are instructions in low-level machine code. It is obvious that in this example, five domains with three intermediate domains are involved. Brooks (1983) further claimed that in order to comprehend a program, a programmer must be able to construct or reconstruct salient information in these domains. This process requires the programmer to acquire information within each domain as well as information between domains. Brook‘s theory of program comprehension can be described as top-down and hypothesis-driven. In practice, the theory claims that a programmer forms hypotheses about the function of the program based on high-level domain and programming knowledge. These hypotheses are further decomposed into subsidiary hypotheses, which are to be verified against the beacons in the program text. For example, a swapping of values between two elements in an array in a program may suggest the presence of a certain kind of sort. Hypotheses are either verified by searching the appropriate beacons or revised or even discarded in the case of absence of beacons. This refinement is done interactively until the whole program is comprehended. Shneiderman and Mayer (1979) suggested a program comprehension model based on the interaction between memory components involved in programming tasks. In their model, program text enters the short-term memory, which is chunked into internal semantic structure using the working memory. The internal semantic structure is multileveled with the highest

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level containing the program goal and the lowest level containing statements or algorithms. The construction of internal semantic structure is helped by the long-term memory. The longterm memory is a knowledge base consisting of syntactic and semantic knowledge. Syntactic knowledge is knowledge about the features and facts of a programming language while semantic knowledge is knowledge about programming constructs and programming concepts. Semantic knowledge, like the working memory, is multileveled. According to Shneiderman and Mayer, this model can also account for programmer behaviour in other programming tasks such as program composition, debugging, program modification, and learning of new programming skills and knowledge. Pennington (1987a; 1987b) showed that when given a program, the first mental representation formed by programmers is a control-flow/procedural abstraction of the program known as the program model. In building this model, two types of knowledge come into play, namely text structure and programming plan knowledge. Text structure knowledge consists of control primes (elementary blocks of code) while programming plan knowledge consists of program plans (typical sequences of programming actions). The model is established in a bottom up manner using beacons to identify control primes and chunk microstructures into macrostructures. After the program model is built, a situation model is developed. This situation model, which represents a data-flow/functional abstraction of the program, is also built bottom up from the program model using domain plan knowledge. Domain plan knowledge represents knowledge in the real world domain that is relevant in the current program domain. Similar to the program model, the situation model consists of chunked plan knowledge that is organized in a hierarchy. Finally, cross-referencing is maintained between the program model and the situation model so that a direct mapping between the two abstractions of program is made possible. In contrast to program comprehension, research in program generation attempts to provide a means to transform plan representation of a program into codes. In this regard, Rist (1989) developed a model of schema creation in programming that shows how programming plans can be transformed into programs. There are four stages in this model. The first stage is the creation of a single line of code. Here, Rist adopted Mayer‘s (1987) conceptualization of a program statement as a transaction. A transaction treats each program statement in terms of the operation taking place, its location, and the objects that are involved. Rist also proposed that a central or focal code fragment that represents the most important operation performed by the line should exist in a line of code. During the second stage, single lines of code are combined to form a program plan. This is done by extending the plan focus to include other plan elements. There are two ways to accomplish the extension process: plan creation and plan retrieval. In plan creation, the plan is obtained backward from the goal to the focus of the plan and to the extension of the plan. The plan is generated from the calculation element to the initialization and the output. In plan retrieval, the plan is obtained forward in schema order from the initialization part of the plan to the calculation part, and finally to the output. In the third stage, basic plans are combined to make more complex plans and this constitutes the visible structure of the complete program. In the final stage, the abstract structure of the program can be analyzed using the role structures of various elements of the program. Role structures of elements describe the goals of elements in terms of input, calculation, and output. Furthermore, Rist (1989) also made claims about the effects of programming knowledge on plan generation strategy. Basically, if knowledge is available, then a plan is generated in a

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forward and top-down manner (schema retrieval). If knowledge is not available, then a plan is generated in a backward and bottom-up manner (focal expansion). It is believed that the former behaviour is common to experts while the latter one is typical among novices. Empirical evidence supported the model proposed by Rist. First, both generation strategies were observed from the subjects. Second, as expertise developed, there was a significant decrease in plan creation and an increase in plan retrieval.

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FUTURE RESEARCH DIRECTIONS Based on above review, we propose some future research directions in the aforementioned strands. Concerning the strand of cognitive consequences and transfer effects of learning of computer programming, we argue that the cognitive load theory (CLT) (Sweller, 1988) is likely to illuminate this strand of research. This theory explains how the human cognitive architecture, in particular our memory system, impacts on learners‘ performance. As suggested by the CLT, there are three kinds of loads, namely intrinsic cognitive load, extraneous cognitive load, and germane cognitive load. Intrinsic cognitive load is inherent from the nature of a task itself. Extraneous cognitive load is resulted from the design and presentation of instructional materials. Germane cognitive load is related to the processing, construction, and automation of schemata. The presence of these loads together with the limitation of human memory impedes our learning to a different extent. There is preliminary work on the application of the theory to study novice programmers (Impelluso, 2009; Yousoof, Sapiyan, & Ramasamy, 2008). However, there are far more questions that remain unanswered. For instance, what are the cognitive loads in a programming process? How do these loads affect students learning to program? How can we reduce these loads to enhance student learning in programming? With regard to our review of studies in this strand, we further suggest that transfer studies may be replicated with the consideration of cognitive load in the learning process. Studies in the strand of the differences between novices and experts reveal that they differ in the ways how knowledge is organized and strategies are deployed. Developing novices‘ programming expertise is by no mean an easy task. A recent review shows that in order to help students to progress towards expertise in programming, educators need to ―adopt a deliberate approach to practice, abstract their ideas, develop cognitive flexibility, elaborate their schema, effectively analyse their context, understand how self management impacts upon their performance, form an expansive world view of learning computing and improve their ability to make control decisions‖ (Bower, 2005, p. 18). These point to the fact that an expert possesses a mix of cognitive and metacognitive strategies. There remains a challenge as to how to help novices to become experts. Among the various models of expertise, the model of domain learning (MDL) (Alexander, 2003) is a well-researched one in diverse learning domains such as history, technology, and music therapy with students from elementary to graduate levels. In essence, it delineates development of expertise in academic domains, encompasses three components (knowledge, strategic processing, and interest), and examines their interplay at three stages (acclimation, competence, and proficiency). Nevertheless, the use of the model in the context of computer programming is almost non-

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existent. As such, it is worthwhile to validate the model empirically in learning of programming in future. In the strand of programming knowledge and strategies, it is evident that most studies conducted in the past assumed that students were able to master relevant knowledge and strategies implicitly through daily teaching. In contrast to this position, we propose that it may be more educational to incorporate knowledge and strategies explicitly into instruction. In fact, de Raadt, Toleman, and Watson (2007) taught students programming strategies explicitly based on the Goal/Plan framework by Soloway (1986) and found some initial success. Yet we call for some large-scale in-depth research on the effectiveness of this approach tested under a design-based research setting (Design-Based Research Collective, 2003). This new research paradigm is ―a systematic but flexible methodology aimed to improve educational practices through iterative analysis, design, development, and implementation, based on collaboration among researchers and practitioners in real-world settings, and leading to contextually-sensitive design principles and theories‖ (Wang & Hannafin, 2005, pp. 6-7). If it is proved effective, it advances our understanding of theory and practice in this strand. Regarding the strand of program comprehension and composition, whereas we agree with Storey‘s (2006) ideas of development of methods, theories, and tools in program comprehension, we further contend that the use of adaptive program comprehension tools could be an important direction for future research since it considers individual characteristics into the design of tools. In fact, it has been demonstrated that the use of an adaptive hypermedia system with two sources of personalization information, learning style and learning behaviour, can significantly improve learning efficacy and efficiency (Tseng, Chu, Hwang, & Tsai, 2008). In practice, these tools can be created by integrating state-of-the-art educational technology with sound learning theory incorporating individual characteristics. With the combined efforts of educationalists and technologists, this new initiative is likely to benefit both students and educators although the efficacy of these tools as a learning aid still merits further investigation.

CONCLUSION This chapter surveys some important studies performed in the four strands of learning and teaching of computer programming (cognitive consequences and transfer effects of learning of computer programming, differences between novices and experts, programming knowledge and strategies, and program comprehension and composition) in the past and identifies some literature-based research directions for future studies. While these recommendations still need further empirical support, such a review provides valuable avenues for researchers and practitioners alike towards advancement in their professions. Unlike other traditional scientific disciplines such as physics, chemistry, and biology, computer science education is still a young and emerging discipline with many unexplored issues and the same applies to programming education. Yet by engaging in computer science education research, we are not only participating but also co-constructing it as a unique research area.

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REFERENCES Alexander, P. A. (2003). The development of expertise: The journey from acclimation to proficiency. Educational Researcher, 32(8), 10-14. Bayman, P., & Mayer, R. E. (1988). Using conceptual models to teach BASIC computer programming. Journal of Educational Psychology, 80(3), 291-298. Ben-Ari, M. (1998). Constructivism in computer science education. SIGCSE Bulletin, 30(1), 257-261. Bernardo, M. A., & Morris, J. D. (1994). Transfer effects of a high school computer programming course on mathematical modeling, procedural comprehension, and verbal problem solution. Journal of Research on Computing in Education, 26(4), 523-536. Bower, M. (2005). Towards the development of expertise in computer science [Electronic Version]. Retrieved November 23, 2009 from http://web.science.mq.edu.au/~mbower/ research/papers/MBowerTowardsTheDevelopmentOfExpertsInComputerScience.pdf. Brooks, R. E. (1977). Towards a theory of the cognitive processes in computer programming. International Journal of Man-Machine Studies, 9(6), 737-751. Brooks, R. E. (1983). Towards a theory of the comprehension of computer programs. International Journal of Man-Machine Studies, 18(6), 543-554. Choi, W. S., & Repman, J. (1993). Effects of Pascal and FORTRAN programming on the problem-solving abilities of college students. Journal of Research on Computing in Education, 25(3), 290-302. Davies, S. P. (1991). The role of notation and knowledge representation in the determination of programming strategy: A framework for integrating models of programming behavior. Cognitive Science, 15(4), 547-572. Davies, S. P. (1993). Models and theories of programming strategy. International Journal of Man-Machine Studies, 39(2), 237-267. de Raadt, M., Toleman, M., & Watson, R. (2007). Incorporating programming strategies explicitly into curricula. In Proceedings of the Seventh Baltic Sea Conference on Computing Education Research (Koli Calling 2007) (pp. 53 - 64). Koli, Finland. Deek, F. P. (1999). The software process: A parallel approach through problem solving and program development. Computer Science Education, 9(1), 43-70. Design-Based Research Collective. (2003). Design-based research: An emerging paradigm for educational inquiry. Educational Researcher, 32(1), 5-8. Dijkstra, E. W. (1989). On the cruelty of really teaching computer science. Communications of the ACM, 32, 1398-1404. Green, T. R. G., Bellamy, R. K. E., & Parker, J. M. (1987). Parsing and gnisrap: A model of device use. In G. M. Olson, S. Sheppard & E. Soloway (Eds.), Empirical Studies of Programmers: Second Workshop (pp. 132-146). Norwood, NJ: Ablex Publishing. Guindon, R. (1990). Knowledge exploited by experts during software system design. International Journal of Man-Machine Studies, 33(3), 279-304. Impelluso, T. J. (2009). Leveraging cognitive load theory, scaffolding, and distance technologies to enhance computer programming for non-majors. Advances in Engineering Education, 1(4), 1-19.

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Jenkins, T. (2002). On the difficulty of learning to program. Paper presented at the 3rd Annual Conference of the LTSN Centre for Information and Computer Sciences, Loughborough, UK. Johnson, W. L. (1990). Understanding and debugging novice programs. Artificial Intelligence, 42, 51-97. Kurland, D. M., Pea, R. D., Clement, C., & Mawby, R. (1989). A study of the development of programming ability and thinking skills in high school students. In E. Soloway & C. S. James (Eds.), Studying the Novice Programmers (pp. 83-109). Hillsdale, NJ: Lawrence Erlbaum Associates. Linn, M. C., & Dalbey, J. (1985). Cognitive consequences of programming instruction: Instruction, access, and ability. Educational Psychologist, 20, 191-206. Mayer, R. E. (1987). Cognitive aspects of learning and using a programming language. In J. M. Carroll (Ed.), Interfacing Thought: Cognitive Aspects of HCI (pp. 61-79). Cambridge, MA: MIT Press. McGill, T. J., & Volet, S. E. (1997). A conceptual framework for analyzing students‘ knowledge of programming. Journal of Research on Technology in Education, 29(3), 276-297. Norris, C., & Jackson, L. (1992). The effect of computer science instruction on critical thinking skills and mental alertness. Journal of Research on Computing in Education, 24(3), 329-336. Palumbo, D. B., & Reed, W. M. (1991). The effect of BASIC programming language instruction on high school students' problem solving ability and computer anxiety. Journal of Research on Computing in Education, 23(3), 343-372. Papert, S. (1980). Mindstorms: Children, computers and powerful ideas. NY: Basic Books. Pea, R. D. (1986). Language-independent conceptual bugs in novice programming. Journal of Educational Computing Research, 2(1), 25-36. Pennington, N. (1987a). Comprehension strategies in programming. In G. Olson, S. Sheppard & E. Soloway (Eds.), Empirical Studies of Programmers: Second Workshop (pp. 100112). Norwood, NJ: Ablex Publishing Corporation. Pennington, N. (1987b). Stimulus structures and mental representations in expert comprehension of computer programs. Cognitive Psychology, 19, 295-341. Perkins, D. N., & Martin, F. (1986). Fragile knowledge and neglected strategies in novice programmers. In E. Soloway & S. Iyengar (Eds.), Empirical Studies of Programmers (pp. 213-229). Norwood, NJ: Ablex Publishing Corporation. Rist, R. S. (1989). Schema creation in programming. Cognitive Science, 13(3), 389-414. Robins, A., Rountree, J., & Rountree, N. (2003). Learning and teaching programming: A review and discussion. Computer Science Education, 13(2), 137-172. Shneiderman, B., & Mayer, R. (1979). Syntactic/semantic interactions in programmer behavior : A model and experimental results. International Journal of Computer and Information Services, 8(3), 219-238. Sleeman, D., Putnam, R. T., Baxter, J., & Kuspa, L. (1988). An introductory Pascal class : A case study of student errors. In R. E. Mayer (Ed.), Teaching and learning computer programming (pp. 237-257). Hillsdale, NJ: Lawrence Erlbaum Associates. Soloway, E. (1986). Learning to program = learning to construct mechanisms and explanations. Communications of the ACM, 29(9), 850 - 858.

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Soloway, E., Bonar, J., & Ehrlich, K. (1983). Cognitive strategies and looping constructs: An empirical study. Communications of the ACM, 26(11), 853-860. Soloway, E., & Ehrlich, K. (1984). Empirical studies of programming knowledge. IEEE Transactions on Software Engineering, 10(5), 595-609. Spohrer, J. C., & Soloway, E. (1986). Novice mistakes: Are the folk wisdoms correct? Communications of the ACM, 29(7), 624-632. Spohrer, J. C., Soloway, E., & Pope, E. A. (1985). A goal/plan analysis of buggy Pascal programs. Human-Computer Interaction, 1(2), 163-207. Storey, M.-A. (2006). Theories, tools and research methods in program comprehension: Past, present and future. Software Quality Journal, 14(3), 187-208. Sweller, J. (1988). Cognitive load during problem solving: Effects on learning. Cognitive Science, 12(2), 257-285. Thurstone, L., & Thurstone, T. (1986). Thurstone test of mental alertness examiner's manual. Chicago: Science Research Associates, Inc. Tseng, C. R., Chu, H. C., Hwang, G. J., & Tsai, C. C. (2008). Development of an adaptive learning system with two sources of personalization information. Computers & Education, 51(2), 776-786. Vessey, I. (1985). Expertise in debugging computer programs: A process analysis. International Journal of Man-Machine Studies, 23(5), 459-494. von Mayrhauser, A., & Vans, A. M. (1994). Program understanding - A survey (No. CS-94120). Fort Collins, CO: Department of Computer Science, Colorado State University. Wang, F., & Hannafin, M. J. (2005). Design-based research and technology-enhanced learning environments. Educational Technology Research and Development, 53(4), 5-23. Watson, G., & Glaser, E. (1980). Watson-Glaser Critical Thinking Appraisal manual. San Antonio, TX: The Psychological Corporation. Wiedenbeck, S., Fix, V., & Scholtz, J. (1993). Characteristics of the mental representations of novice and expert programmers: An empirical study. International Journal of ManMachine Studies, 39(5), 793-812. Winslow, L. E. (1996). Programming pedagogy - a psychological overview. SIGCSE Bulletin, 28(3), 17-22. Yousoof, M., Sapiyan, M., & Ramasamy, K. (2008). Proposed framework to manage cognitive load in computer program learning. In Proceedings of the 7th WSEAS International Conference on Artificial intelligence, Knowledge Engineering and Databases (pp. 50-55). Cambridge, UK: World Scientific and Engineering Academy and Society (WSEAS).

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Chapter 4

PROVIDING SCENARIO-BASED, MULTI-DISCIPLINARY, DISASTER EDUCATION: THE SUCCESSIVE APPROXIMATION APPROACH Kelly Burkholder-Allen, Paul Rega, Christopher Bork and Churton Budd University of Toledo, Toledo, Ohio

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ABSTRACT The traditional approach to disaster education lacks depth. Curricula are often comprised of a collection of the ―hazard du jour‖ and presented in the traditional didactic lecture format to an audience of individuals from a single discipline. While the key concepts presented may provide sufficient knowledge for successful completion, there is ample research to demonstrate that the preponderance of professionals who successfully complete these traditional, lecture-style programs consider themselves ill-prepared to respond to incidents [1]. Additionally, recent reports indicate that healthcare providers, hospitals, health systems, cities, states, and the country as a whole scored poorly in preparedness for a catastrophic health event [2-5]. These shortcomings may be related to the learning environment and didactic approach in which most disaster education is conducted. A learning environment that is static, one dimensional, non-interactive, and introduces content in black and white only, does not reflect the spontaneous, dynamic, and multidimensional incidents that our responders are called upon to manage in living color. We find this practice to be unacceptable and offer an alternative approach. Although the traditional approach to disaster education may enhance the adult learners‘ knowledge-base on a given hazard, it often lacks the ability to enhance critical decision-making and other skills that improve their ability to effectively manage an incident. Management of emergencies and disasters takes place on multidisciplinary, multiagency, multijurisdictional levels and is predicated on a systematic approach which manages by objectives. The five-step process used in this management approach includes establishing incident objectives, developing strategies based on the overarching incident objectives, developing assignments, plans, and procedures, establishing measurable tactics for functional activities, while providing direction to attain those tactics, and

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documentation of results in order to measure performance and to facilitate corrective action. A multidisciplinary, systematic, and proactive approach is the foundation of National Incident Management System (NIMS) [6], which provides guidance to jurisdictions so that they may work together in a seamless manner to protect against, respond to, recover from, and mitigate the effects of incidents. NIMS integrates the best practices into a comprehensive framework and provides a template for incident management for emergency management and response personnel in the context of all-hazards, working in conjunction with the National Response Framework (NRF) [7] National Incident Management System]. The ―systems approach‖ is also supported by the National Health Security Strategy (NHSS), recognizing that many interrelated systems are critical to support health at the individual and community levels and to protect them and support their recovery from an incident [8]. Overall, the strategic objectives of the NHHS support the significance and relevance of scenario-based training by 1) 2)

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3) 4) 5) 6) 7) 8) 9)

highlighting the importance of fostering informed and empowered individuals and communities; developing and maintaining a well-trained workforce, ensuring situational awareness; fostering integrated, scalable healthcare delivery systems; ensuring timely and effective communications; promoting effective countermeasures enterprises; ensuring prevention/mitigation of environmental and emerging health threats; incorporating post-incident recovery into planning and response; working with partners across the border and around the globe; and finally, by ensuring that all systems which support the security of our Nation‘s health are grounded in science, evaluation, and quality improvement methods.

It is essential that emergency management /response personnel possess the requisite knowledge, skills, and abilities to optimize personal performance and contribute to the overall successful management of disasters. Emergency responders is a broadly defined category and collectively includes individuals from Federal, State, territorial, tribal, regional, and local governments, non-governmental organizations (NGO‘s), private sector organizations and industries, critical infrastructure/key resource owners and their operators, and individuals from any organization, or persons who assume any role in emergency management [NIMS]. The quality and overall effectiveness of disaster education and training provided for emergency responders would be greatly enhanced if the delivery transitioned beyond the current traditional didactic approach to a more dynamic, multidisciplinary, and multidimensional approach. It is believed that this vision can be realized by offering scenario-based education that engages learners as active, rather than passive, participants in the process of enhancing their knowledge, skills, and abilities as a responder. This chapter explores the concept of scenario-based education using the ―Successive Approximation‖ approach for providing disaster-related education to our Nation‘s current and future responders.

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INTRODUCTION Sentinel events occurring in the mid-1990‘s, provided the impetus for directing billions of dollars toward disaster-related training and education for our Nation‘s responder community and public health infrastructure. The Oklahoma City bombing in 1995, the World Trade Center Bombings of 1993 and 2001, and the Anthrax attacks in 2001, highlighted the vulnerability of our country to acts of terrorism and the urgency for building readiness capacities. As a result, responders from the law enforcement, fire service, and EMS communities, public health, hospital, and healthcare professionals at the local, state, and national levels were suddenly bombarded with training and educational opportunities and funding for equipment to strengthen ournational readiness for Weapons of Mass Destruction (WMD) events. From the WMD theme emerged an emphasis on the recognition, treatment, and management of casualties of Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) events, and a more recent inclusion of Pandemic Preparedness activities, as the novel viruses, H5N1 and H1N1 surfaced. Countless academic institutions, federal agencies, professional societies, and other professionally recognized and credible entities contributed to or independently developed and implemented training and educational initiatives focused on CBRNE and, to a lesser extent, Pandemic Preparedness. Although these specific training and education initiatives have been widely accepted among the professionals within the target professions as providing the necessary knowledge for successful course completion, they have not adequately prepared the learners to actually respond to incidents [3]. Knowledge of specific chemical, biological, radiological, nuclear, and explosive agents alone does not predict the effective management of an actual CBRNE incident. Knowledge is just one element of the ―knowledge, skills, and abilities‖ triad essential for effective response and management of an incident. Disasters of any type and magnitude are dynamic incidents requiring multi-agency, multidisciplinary, and most likely, multijurisdictional response to be effectively managed. Disaster management is approached systematically and comprehensively, incorporating all aspects of the cycle‘s mitigation, preparedness, response, and recovery phases. Disaster education should use the same approach. Ideally, disaster education curricula should be designed based on the principles of standardization and interoperability. It should establish a fundamental ―all-hazards‖ knowledge base which will provide the foundation from which content related to specific agents and types of incidents can be layered. As the responders‘ knowledge is enhanced, so too should their skills and abilities be enhanced [9-10]. In order to accomplish this, the authors propose a paradigm shift, transitioning from the traditional approach of demonstrating ―what we have learned‖ by successful completion of a post-test to providing the responders with opportunities to demonstrate ―how we use what we have learned‖. The authors are advocates for utilizing a scenario-based approach, which successively approximates real-world incidents, thus providing a medium for responders to test their knowledge, skills, and abilities to manage these incidents in an interactive, comprehensive, multidisciplinary, multidimensional, and low consequence environment. The approach is by no means innovative, but is seemingly under-utilized in the science of disaster education. Courses using a similar methodology have been considered the gold standard in healthcare and many professions for decades. Why this approach has not been

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readily apparent in the construct of disaster education for responders can only be speculated, especially because it can be found in even in common courses that many of us been participants in: Drivers‘ Education. Drivers‘ Education is a generic example of a ―gold standard‖ course which successfully combines didactic and experiential learning. The intended outcome of a comprehensive approach is to provide the new driver with the requisite knowledge on traffic laws and vehicle safety, safe driving skills, and ability to effectively combine these elements with critical thinking as he faces new and unusual situations behind the wheel. Neither the didactic nor the experiential element is mutually exclusive and successful achievement of both is critical to providing the new driver with the requisite knowledge, skills, and abilities to safely operate a vehicle. We find that the lack of a ―gold standard‖ approach to disaster training and education to be totally unacceptable. A further call to action for adopting the scenario-based ―successive approximation approach as a gold standard in disaster training and education and is best articulated in the Exercise and Evaluation Guide for Public Health Emergency Preparedness, ―The ultimate test of proficiency for emergency responders and the systems in which they operate is an actual disaster. Fortunately, disasters happen rarely, so responders must find alternate ways to practice their skills. The best forms of practice are exercises and drills that simulate reality as closely as practicable. The true value of exercises lies in the opportunities they offer to practice skills and make mistakes in a low-cost, low-risk, low-consequence environment compared with real catastrophes.‖ [11] Currently, so many of the key elements are already in place. There are a variety of disaster and CBRNE curricula from which content can be drawn to either provide the basic foundation of knowledge or to augment a responder‘s current knowledge base. The National Response Framework, the National Preparedness Guidelines, The National Planning Scenarios, and affiliated Target Capabilities provide the guidance and metrics for scenario-based education planning and evaluation. Similarly, the National Incident Management System (NIMS) provides the basis for interoperability and compatibility, enabling a diverse group of responders to operate in a well-integrated and effective manner. Using these existing tools to design and implement scenarios, in the form of facilitated discussions, tabletop, and functional exercises, which are built upon successive approximations of real-world events can provide the bridge between didactic and experiential education and fill in the gaps which are created by the single-discipline, single hazard, onedimensional approach. A scenario-based approach offers a mutual starting point from which to launch an interactive, multidisciplinary, and multidimensional approach to learning and is one that has been successfully utilized at The University of Toledo for nearly two decades.

OUR HISTORY OF PROVIDING SCENARIO-BASED DISASTER EDUCATION The initial, first-hand experience we had with development and implementation of a scenario-based course occurred in the early 1990‘s when the Director of the Paramedic Program at The University of Toledo Community and Technical College presented us with an opportunity to develop and implement a multi-disciplinary disaster course. The design of the proposed course was ours to determine; enrollment was open to the university students as an

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elective equal to three credit hours and as a continuing education course open to first responders and members of the Emergency Management community. Our attendees represented a wide variety of disciplines, agencies, and levels of experience and included: paramedic students, firefighters and command staff, 911 dispatch personnel, EMS providers, the County EMS Director, emergency management personnel, including the both the County EMA Director and Deputy Director, and personnel from the County Sheriff‘s Department. Throughout the development and implementation stages for Introduction To Disasters: Theory And Practice, we relied upon our years of literature research on disasters, the many ―lessons learned‖ from our experiences responding to disasters with the National Disaster Medical System (NDMS), and the lessons of others as our guide. Having a blank slate from which to begin and an entire semester‘s worth of in-classroom time, we developed an allhazards curriculum built upon the principles of disaster management and the Incident Command System. The curriculum included: 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 15) 16) 17) 18) 19) 20) 21)

the phases of a disaster, categories of disasters Hazard analysis disaster management, Triage, field medical response, hospital response, incident Command System (ICS), the epidemiological aspects of disasters, hazardous materials, media relations, patient care, disaster injury patterns, the medical consequences of simple, extended, and complex disasters, Critical Incident Stress Management (CSM), The Federal Response Plan, The anatomy of a disaster, terrorism and WMD‘s: chemical, biological, and radiological, agents, personal and family preparedness, continuity of operations, and a variety of natural, man-made, technological, and intentional disasters and their consequences.

Our students were assigned readings selected from a wide variety of professional journals, FEMA publications, and books which provided them with a well-rounded perspective on disaster management and response. If a developing event occurred during the semester, we provided Situation Reports and other real-time intelligence from our sources within the agencies involved, reviewed news articles and initiated discussion in class about what had transpired and how the response could be managed better. Classes included didactic material and facilitated discussions which were based on real world events, evolving disasters, and scenarios that we created to provide opportunities for group interaction, handson activities, exercise of critical thinking, and collective problem-solving skills. To capitalize

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on the unique perspectives and professional experiences of the individuals in our class, ICS roles were rotated, placing the students in unfamiliar roles in which they gained a new perspective. The seasoned professionals offered support and guidance to classmates lacking practical experience both during the scenarios and the post-scenario discussion (hot-wash). A variety of scenarios were employed, each accompanied by group activities. For ―triage or ―mass casualty incidents‖ themed classes, paper patients were used to practice triage skills. In scenarios where ICS or ―on-scene management‖ was the theme, Matchbox cars and emergency vehicles were used in conjunction with a carpet depicting a city, allowing students to configure and manage the incident. The class took a field trip to the local Emergency Operations Center (EOC) which provided a realistic venue from which we conducted another scenario. A local aero-medical evacuation program landed their helicopter on campus and the students practiced setting up a landing zone. Mock interviews were conducted by a local television reporter as the students assumed the role of the Public Information Officer (PIO) during a ―media relations‖ themed class. Low-fidelity adjuncts, including maps, accountability boards, two-way radios, sound effects, and other props and special effects aided us in our efforts to approximate real-world conditions. Throughout the semester, written quizzes were used to evaluate student progress in learning key concepts that were presented and to give feedback to the instructors that our teaching methods were or were not being effective. The final exam consisted of individual or small-group projects chosen by the students: analysis of a disaster plan from a response agency outside of the county in which the student resided, coordinating and presenting the initial response to a disaster scenario provided by the instructors, or researching a disaster or interviewing a disaster responder or victim. This course was well received by the students, as evidenced by their positive feedback on end-of- semester evaluations. Scores from the PreTest and Post-Test also provided evidence that the students‘ knowledge of basic concepts associated with disaster management and response had increased. As with most niche courses, student interest waned after a few years and this initial course was discontinued; however, we have used many elements of the original curriculum as a template for conducting scenario-based education to multidisciplinary audiences at local, regional, national, and international venues since. The original curriculum template, circa 1995, has undergone numerous revisions and enhancements, in order to keep it on cuttingedge and allow for presentation on multi-media platforms. Our comprehensive scenario-based courses, and focused courses have been conducted at the university-based and communitybased levels for hospitals, EMS providers, healthcare systems, medical students, resident physicians, nursing students, Physician Assistant students, Disaster Medical Assistance Team (DMAT) responders, Metropilitan Medical Response System (MMRS) and Regional Medical Response System (RMRS) stakeholders, and a host of traditional and non-traditional responders such as librarians. The fidelity of our scenario-based approach and use of successive approximations has amplified throughout the years as technology has advanced. We have had funding and developed working relationships with faculty and departments specializing in the use of creative technology in education. In 2009, we developed and conducted Pile Up, a program for community-based responders as the targeted audience. While we were facile with creating scenarios and challenging our students to participate in the approach and resolution of a fictitious incident, we were hamstrung with the inability to

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create a table-top exercise set in an actual location. In addition to that, with no actual scene to work from, there was no ownership by participants to manage the situation. However, with advances of technology and the services of the University of Toledo‘s Center for Creative Instruction, we devised a multimedia table-top exercise where an actual geographic location was imaged from satellite technology. That site was an Interstate Highway on which a major MCI (Mass Casualty Incident) would be created using animation and computer generated special effects. A panel of experts who would normally be involved with an MCI at that specific geographic site was invited to serve as players and subject matter experts. We presented them with a scenario and asked them to respond in real time concerning their interaction and management of the scene. These experts included:

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1) 2) 3) 4) 5) 6) 7)

Highway Patrol officers Interstate highway management personnel An Emergency physician An Air ambulance pilot An EMS representative from the jurisdiction The Fire Chief from the jurisdiction. A local television reporter

In order to enable the expert panel to demonstrate how they would organize and stage resources, secure the scene, stage and respond to the event icons were developed which could be manipulated by the computer‘s mouse. The icons included fire apparatus, ambulance, helicopters, command post, barricades, field hospital zone, staging area, helicopter landing zone, responders, and victims. As the scenario was presented to the participants, the experts‘ actions were recorded by the manipulation of the symbols upon the map. The facilitator drove the scenario and asked questions of the experts in order for them to expound upon their choices and decisions. Simultaneously, the audience, who were given remote response units that recorded their answers to specific questions (e.g. triaging a specific patient as emergency, urgent, or non-urgent) or to register their opinion about what a panelist had just presented, were invited to engage in play. For each question or response the percentages of the audience‘s responses were presented on the screen for discussion among the panelists. This interactivity between panelists and screen and between experts and audience allowed for a dynamic interplay among all concerned and made disaster management more real than imagined. The development of this concept was unique not only to the university but also in the region. In addition, the expense to produce the entire three hour event cost less than three thousand dollars. The relatively low cost of the innovative learning experience and the positive feedback that was received has energized the notion that this approach to learning can be easily and economically developed for other types of disasters using the actual locations managed by the actual responders The authors have provided scenario-based disaster education, using the successive approximation approach to community-based responders with more frequency and consistency to community-based audiences than audiences from within our university. For the past 15 years, the authors have at times, been paid for conducting courses by a variety of local and state agencies; recipients of Assistant Secretary for Preparedness and Response (ASPR)

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Hospital Preparedness, Homeland Security Grant, Area Health Education Centers (AHEC) funds, in addition to other funding sources. The continued interest in our courses and the limited funding that we have received validates not only our approach to providing disaster education, but the scenario-based approach as well. Unfortunately, our success in providing scenario-based disaster education at The University of Toledo has been more challenging. In the late 1990‘s we received an invitation from the School of Medicine‘s Emergency Medicine Club to provide disaster education to club members. Noting the absence of disaster education within their own medical school curriculum, several of the students conducted a survey of medical schools in the U.S. and found this educational deficit to be a common theme in medical education [12,13]. The survey findings prompted meeting with the Dean and other key faculty within the School of Medicine and the inclusion of a mandatory, eight hour class devoted to topics in disaster medicine. The class was also attended by resident physicians, students from the Schools of Nursing, and Allied Health Sciences for several years. The authors have been and continued to be called upon to provide focused lectures on specific disaster-related topics to students in many health care disciplines on our Health Science Campus. Most recently the authors have utilized mini table top exercises as an approach to teach ICS more interactively. Student who completed one of the sessions in April 2009 noted that the scenario they addressed and the expected actions were almost identical the to CDC and DHS response to the H1N1 outbreak the following week. Again, although we have made some progress, there is still much to be done to provide students on the University of Toledo Health Science Campus with a comprehensive disaster management/medicine curriculum that is integrated and interdisciplinary. Our overarching goal is to provide our Health Science Campus students with the requisite knowledge in the science of disaster management, skills, and abilities, which will best prepare them to effectively respond to a full spectrum of emergencies and disasters. Cognizant of the fact that each and every one of our students on the Health Science Campus, by virtue of chosen course of study, may be called upon to perform response activities, we recognize that a coordinated and comprehensive methodology for such a major undertaking is critical. Our strategy is based on using an incremental approach to introducing content and imbedding it into existing discipline-specific curricula. The initial phase includes the introduction of ―awareness- level ―disaster education content for all University of Toledo Health Science Campus students, followed by discipline-specific content and multi-discipline, scenario-based classes and activities. ―Awareness- level‖ content will be drawn from existing material and provide an all-hazards overview of disasters and disaster management. Awareness-level content can be delivered as an online requirement or incorporated into the curriculum of introductory-level courses within each discipline would provide a basic foundation of knowledge from which to build upon. More in-depth and discipline-specific content would be integrated into existing curricula by inclusion in lecture format or as an online adjunct to course materials. Content in this phase will prepare students to participate in tactical level of response. And although content delivery would be integrated within the existing curricula of each discipline-specific school, this content will be varied only in the level of depth and degree of specialization. Interactive scenarios available online and in the form of games will allow students to role play, practice using the Incident Management System (IMS), while allowing them to engage in a simulated tactical response. Review of Emergency Management Plans for hospitals and health care

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institutions can be accomplished during clinical rotations and will provide a broad overview of their expected level of participation in a real-world event. The final phase will provide with the forum in which students from every discipline will be called upon to apply disaster management and disaster medicine knowledge, practice skills, and apply critical-thinking as they work together responding to scenarios successively approximating real world events. Beginning with simple drills and facilitated discussions, the lessons will be progressing incrementally to more complex scenarios delivered in the tabletop or functional exercise format. At this level, the scenario-based education will take place incrementally throughout an academic year. It is critical that a discussion of lessons learned and corrective action planning take place at the group level at the conclusion of each scenario, so that forward progress is based on confident and effective management of all aspects of the incident. To inject realism and successively approximate real world events scenarios, the students will be guided as they operate under NIMS and be required to complete appropriate NIMS forms. Both students and faculty will serve as evaluators, using the Homeland Security Exercise Evaluation Program (HSEEP) guidelines as a basis for measuring progress providing direction for improvement planning. At this time, our goal remains challenging but not insurmountable. There are countless issues that have prevented us from making progress towards achieving this goal, with the most prominent being the lack of funding. Another issue is the fact that the existing curricula in most disciplines lacks the flexibility necessary for content additions and revisions and often the support from the academic bodies that develop or accredit them. Additionally, the concept, in order to be successfully implemented, would require a campus-wide paradigm shifting and an unprecedented level of cooperation, coordination, and buy-in. In today‘s environment of departmental downsizing, decreases in funding streams for academia, and faculty continuously be called upon to do more with less, it will be years of challenges before we will be able to fully actualize our concept. Nonetheless, the authors maintain the belief that scenario-based disaster education using the successive approximation approach must become the gold standard for our Nation‘s responders, and it should take place in Universities and Academic Centers.

UNIVERSITIES AND ACADEMIC CENTERS ARE IN THE POSITION TO TAKE THE LEAD Whether the scenario-based approach education is initiated at the community or university level, the successive approximation approach can be implemented. Universities and academic centers are positioned to take the lead in the development and implementation of scenario-based disaster education, using this successive approximation approach. Universities and academic centers already have many of the necessary elements in place and can develop and implement courses incurring minimal start-up costs. Expertise in the areas of: instructional design, technology, research, statistical analysis, and in a variety of scientific and behavioral disciplines, can be drawn from faculty. Remaining gaps in expertise can be filled by adjunct faculty with targeted recruitment from the response community. Universities and academic centers also provide the ideal venue from which to conduct the educational offerings, as they have large lecture halls and auditoriums capable of

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accommodating large groups, props , equipment, and simulators. Lecture halls at this level are technologically advanced and capable of incorporating multimedia applications. The initial step, in the development and implementation of scenario-based education, regardless of the composition of the intended audience, should be conducting a gap analysis. This crucial step will assist in determining the strength and integrity of the fundamental disaster management knowledge present in the intended audience and provide insight into their proficiency in associated skills and abilities. The gap analysis will serve as the foundation from which goals, objective, content and scenarios will be developed, implemented, assessed and refined. In a community-based approach, the gap analysis is critical in determining the current state of readiness at the jurisdictional, agency, and individual levels. The first step of the gap analysis includes an extensive review of After Action Reports (AARs) from real-world incidents and previous exercises that have taken place within the jurisdiction. The AAR review will yield information regarding the overall level of readiness by providing crucial details in the defined areas of strength, areas needing improvement, and how the defined areas of improvement are being managed and tracked in the current Improvement Plans (IPs). These documents will also provide an overview of the agencies and disciplines that comprise the community‘s responders and public health infrastructure and their level of readiness. From there, gaps in disaster-related knowledge, skills, and abilities of the individuals in the various responder disciplines can be assessed to identify areas of concentration for curriculum selection and scenario development. Knowing who the players are, their level of knowledge, experience, and skill proficiency, and how well they function together will also help determine the starting point. The goal is to build upon the foundation to make the jurisdiction and its responders stronger and more resilient. Scenario-based education should provide challenges and opportunities to draw from fundamental knowledge and experiences to build capacity. It may be appropriate for the intended audience to begin their scenario-based education with a table top exercise format rather than a facilitated discussion, and in some circumstances, a functional exercise format may best fit the higher level of knowledge, skills, and abilities of a well-seasoned group. The university-based approach requires a gap analysis of a different nature, as most students will have limited if any prior experience as responders. Given their almost certain lack of knowledge, skills, or abilities related to disaster management and practical experience within their chosen professional field, the basic didactic educational elements should be frontloaded. The intended purpose is to provide a consistent knowledge base and a foundation from which to build skills and abilities. In this case, the gap analysis could be performed at the disciplinary or individual college level by reviewing current curricula for existence/inclusion of disaster-related materials and the context in which they are presented. A university with a medical school and schools of nursing, physical therapy, physician assistant programs, and other allied health professions, should consider a global review of disaster-related content in core curricula in order to determine commonalities and opportunities for developing or including multidisciplinary courses or skills labs where the scenario-based approach could be utilized. A multidisciplinary task force that includes faculty members from each of the disciplines will be essential in developing and vetting the content. Ultimately, this would promote collegiality among the disciplines and afford the students and faculty members insight into the roles and complex working relationships that they assume as responders. The entry point for scenario-based education may be the delivery as a low stress

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drill or in facilitated discussion format. This will engage them and promote active participation through mutual problem-solving. As they progress to more difficult and demanding scenarios, they will be able draw from their growing knowledge base, scenariobased ―lessons learned‖, and critical thinking skills. This approach will give tomorrow‘s responders an advantage as they enter the professional workforce.

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CONCLUSION The Homeland Security Presidential Directive (HSPD)-8, ―National Preparedness‖, which includes the National Preparedness Goal and the National Exercise Program, scenarios provide the foundation for identifying capabilities across all mission areas. Scenarios are designed such that certain common functions must be accomplished and to prompt responder organizations to move quickly and in a coordinated fashion. As part of this initiative fifteen National Planning Scenarios have been developed as planning tools. They are ―all hazard‖, encompassing a wide range of potential acts of terrorism and natural disasters provide a common foundation for exercise Scenarios delivered in a high, medium, or low fidelity format will provide responders opportunities to apply fundamental knowledge and test proficiency of critical decisionmaking and other requisite skills in a dynamic, interactive, and multi-disciplinary learning environment, utilizing readily available multimedia platforms and technological adjuncts: satellite imaging, group/videoconferencing, and other applications enable participants to put into practice a variety of strategies and tactical methodologies to manage evolving incidents and events in a simulated real time and low-risk environment. The scenario-based process will aid in the identification and analysis of vulnerabilities in targeted capabilities and promote corrective action planning by building upon successes, and fostering a systems approach to emergency and disaster management. The effectiveness of these methodologies can be validated in scenario-based education developed, delivered, and evaluated based on use of the National Preparedness Guidelines, the National Response Framework, NIMS, and the Homeland Security Exercise Evaluation Program. The benefit to emergency and disasters responders at the agency or jurisdictional level is the ability to assess and track readiness based on outcome oriented and measurable performance metrics that are in alignment with Federal policies and doctrine, industry standards, planning guidance, and applicable laws and regulations. The capabilities planning of the fifteen National Planning Scenarios (NPSs) provide a mutual starting point from which to identify capabilities across all mission levels and target levels and may serve as launching pad. Target Capabilities are identified tasks to be performed in order to prevent, protect against, respond to, and recover from the all-hazard NPS‘s. The National Preparedness Guidelines and Target Capabilities List (TCLs) drive the preparedness cycle by answering foundational preparedness questions: How prepared are we? How prepared do we need to be? What should we do to close the gaps? [14,15]. Scenario-based education based on the National Preparedness Guidelines and Target Capabilities List, that is multidisciplinary, multiagency, and multijurisdictional provides the disaster/emergency managers and responders the forum in which to answer these questions as they their community‘s disaster preparedness cycle.

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Applying the successive approximation approach is limited its scope only by the imagination and available resources of the educators. The scenario-based education utilizing the successive approximation approach that has been developed and implemented at The University of Toledo provides just but one snapshot in the evolving process of enhancing the science of disaster management. There is much work yet to be done in order to provide our Nation‘s public health and emergency responders with comprehensive, multidisciplinary, multi dimensional education that will enhance their knowledge, skills, and abilities to effectively prepare for, mitigate, respond to, and recover from 21st Century hazards; thus increasing resilience at the local, state, and federal levels.

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REFERENCES [1] Center for Biosecurity of UPMC. The next challenge in healthcare preparedness: catastrophic health events. Prepared for the US Department of Health and Human Services under Contract No. HHSO100200700038C. 2009. Report US Department of Health and Human Services Information on disaster preparedness. [2] Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism. Report Card: Government Failing to Protect America from Grave Threats of WMD Proliferation and Terrorism: An Assessment of the U.S. Government‘s Progress in Protecting the United States from Weapons of Mass Destruction Proliferation and Terrorism. January, 2010. http://www.preventwmd.gov/static/docs/report-card.pdf [3] Hartwig KA, Burich D, Cannon C. Critical challenges ahead in bioterrorism preparedness training for clinicians. Prehosp Disaster Med. 2009;24(1):47-53. [4] Maguire BJ, Dean S, Bissell RA, et al. Epidemic and Bioterrorism Preparation among Emergency Medical Services Systems. Prehosp Disaster Med. 2007;22(3):237-242. [5] Williams J, Nocera M, and Casteel C. The Effectiveness of Disaster Training for Health Care Workers: A Systematic Review. Ann Emerg Med. 200;852(3):211-222. [6] Department of Homeland Security. National Incident Management System. 2008. Department of Homeland Security, Washington, DC. [7] Department of Homeland Security-FEMA. National Response Framework. http://www.fema.gov/pdf/emergency/nrf/nrf-core.pdf accessed 1-17-2010. [8] US Department of Health and Human Services. National Health Security Strategy of The United States of America. December, 2009. http://www.phe.gov/ Preparedness/planning/authority/nhss/strategy/Documents/nhss-final.pdf. [9] Barbera JA and Macintyre AG. Medical and Health Incident Mangement (MaHHIM) System: A Comprehensive Functional System Description for Mass Casualty Medical and Health Incident Management. Institute for Crisis, Disaster, and Risk Management, The George Washington University. Washington, D.C., October 2002. Supported by a grant from the Alfred P. Sloan Foundation. [10] Markenson D, DiMaggio C, and Redlener I. Preparing Health Professions Students for Terrorism, Disaster, and Public Health Emergencies: Core Competencies. Academic Medicine. Vol. 80, No. 6/June 2005. [11] Bradshaw CC and Bartenfeld TA. Exercise Evaluation Guides for Public Health Emergency Preparedness. Homeland Security Affairs. 2009;5(3):1-45.

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[12] Colombo, J.B., Peterson, W., Thackeray, J., and et al: Disaster Medicine Education in Medical School Curricula. Ann Emerg Med; 35(5) s.45 (abstract). Poster presentation at the 8th International [13] American Medical Association. Report 15 of the Council on Medical Education (A-09) Education in Disaster Medicine and Public Health Preparedness During Medical School and Residency Training. 2009. http://www.ama-assn.org/ama1/pub/upload/mm/377/ cme-report-15a-09.pdf [14] U. S. Department of Homeland Security. Target Capabilities List: A Companion to the National Preparedness Guidelines. September, 2007 http://www.fema.gov/pdf/ government/training/tcl.pdf [15] Department of Homeland Security and Federal Emergency Management Agency Target Capabilities Users Guide. February, 2009. http://www.iaem.com/committees/ GovernmentAffairs/documents/TargetCapabilitiesUserGuide_17February2009.pdf.

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Chapter 5

A PSYCHOLOGICAL PERSPECTIVE ON MEDIA LITERACY M. M Terras*, J. Ramsay and E. Boyle School of Social Sciences, Faculty of Health, Education and Social Sciences, University of the West of Scotland, Paisley, PA1 2BE

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ABSTRACT In today‘s technology-driven society, the ability to effectively use information and communication technology (ICT) is essential in an educational context. The ability to ―access, understand and create communications in a variety of contexts‖ (Ofcom, 2009, pg 4) is known in the UK as Media Literacy. To date, research on media literacy has focused primarily on the impact of demographic factors such as age, gender and socioeconomic status. Apart from personality factors, the key role that Psychological factors play in media literacy has been overlooked. When viewed through a Psychological lens it is clear that all three components of media literacy: access, understanding and creation require in-depth examination both separately and in combination. This analysis applies at both the theoretical level and the empirical level. We ask: how Psychologically valid are current conceptions of media literacy? How accurately do they reflect perceptions and experiences of media use? We propose that the consideration of the psychological dimensions of media literacy skills is crucial if we are develop and full understanding of media literacy skills and capitalise on the learning potential of Web 2 technology. In this paper we highlight how Psychological theory and research has previously contributed to our understanding of our interactions with technology, the process of learning and consider how psychology can contribute to our understanding and application of new technologies within education. As a discipline with the objective of understanding behaviour, the consideration of the Psychological dimensions of Media Literacy is crucial for both education and society.

* All affiliated to UWS and please send correspondence to Dr MM Terras: Tel: 0141 848 3954, Email: [email protected]

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INTRODUCTION In today‘s technology-driven society, the ability to effectively use information and communication technology (ICT) is essential in an educational context. Initially ICT applications were used as a means of supporting learning activities such as word processing and communication via email. However, the advent of Web.2 technology (e.g. social networking, weblogging and wikis) offers an immense range of new opportunities for ICT not only to support the educational process but also to become an integral part of learning and teaching (Greenhow, Robelia & Hughes, 2009). Learning horizons are no longer restricted by constraints on time, location and physical resources (e.g. library opening hours and the physical availability of books): the internet with its vast repository of information enables people across the globe to access information in a way which is unprecedented in history. If today‘s learners are to maximise these opportunities then they require the skills that enable them to read and write texts on computer screens of varying shapes and sizes, in a range of work, educational and social contexts of use, follow hyperlinks, and navigate their way through a vast amount of information, some of better quality than others. In sum, they need to be media literate. In the UK, Media Literacy is defined as the ability to ―access, understand and create communications in a variety of contexts‖ (Ofcom, 2009, pg 4). In this paper we suggest that the contribution of Psychological factors (both cognitive and psycho-social) to the development and implementation of media literacy skills has been largely been overlooked, and propose that a more in-depth understanding of the Psychological factors that support and hinder effective media literacy skills both within education and in society generally is required. Literacy and the development of literacy skills lie at the core of education. Debate concerning the ability to ―access, understand and create communications‖ in the digital age to a certain extent reflects issues similar to those from a traditional print literacy perspective. However, media literacy also poses some new and unique challenges to learners: the ability to access, understand and create may require a different (and possibly overlapping) skill set from traditional literacy. While traditional literacy focuses on the ability to understand or produce written language, media literacy refers to the ability to use a broader range of media-based technologies which offer a wider range of activities and skills in producing and receiving communications. These communications include both spoken and written language as well as picture-based communication, email, texting via mobile phone and voicemail. When viewed through a Psychological lens it is clear that all three components of media literacy: access, understanding and creation require in-depth examination both separately and in combination. This analysis applies at both the theoretical level and the empirical level. We ask: how Psychologically valid are current conceptions of media literacy? How accurately do they reflect perceptions and experiences of media use? We propose that the consideration of the psychological dimensions of media literacy skills is crucial if we are develop and full understanding of media literacy skills and capitalise on the learning potential of Web 2 technology. In this paper we will highlight how Psychological theory and research has previously contributed to our understanding of our interactions with technology, the process of learning and consider how psychology can contribute to our understanding and application of new technologies within education.

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UNDERSTANDING INTERACTIONS WITH TECHNOLOGY: PSYCHO-SOCIAL FACTORS Psychological theory has long been applied by technology developers to inform the design and improve the usability of interactive software. For example, mental models (Johnson-Laird, 1983), cognitive load (Schweller, 1988; Young, Green and Simon, 1989), cognitive walkthroughs (Carroll and Rosson, 1992; Wharton et al, 1994), cognitive modelling (Barnard and May, 1993), and cognitive task analysis (Hakos and Redish, 1998) to name a few. Current effort in Human-computer Interaction (HCI) research is concerned with understanding the individual differences that determine the ability to cope with different media, and the cognitive, emotional and socio-psychological barriers and enablers to technology use. The psychological theories and concepts that are being successfully mobilised in the quest to understand new media use include, but are not limited to personality theory (e.g. Costa & McRae, 1988), locus of control for reinforcement (Rotter, 1966) need for cognition (Cacioppo and Petty, 1982), working memory capacity, reading/literacy ability, executive function and self-esteem (e.g. Rosenberg, 1965). With respect to self-esteem a newly developed typology of orientations to email: ‗relaxed‘, ‗driven‘ and ‗stressed‘ demonstrates how low self-esteem is associated with the ‗driven‘ orientation to email and a ‗stressed‘ orientation is linked to perceiving email as being distractive (Hair, Renaud and Ramsay, 2006). Low self-esteem has also been linked to internet addiction (Armstrong, Phillips and Saling, 2000) and female online gaming (Funk and Buchman, 1996). Minsky and Marin (1999) reported that being more open to change, along with high levels of computer self-efficacy were implicated in email use. Self-esteem has long been recognised as an influential factor in academic achievement therefore the role it plays in on-line learning is worthy of further investigation. Bandura (2002) highlights the importance of self-efficacy in supporting the ability to use technology and develop effective media literacy skills and the opportunities that it affords, to maximise our potential and well-being in a wide range of contexts such as education, health, work and social opportunities. The increasing availability of information only in digital form highlights the significance of media literacy skills as without them individuals will be excluded not only from education but from wider society. A natural extension, the relationship between academic achievement and media literacy skills, is now starting to receive much needed research attention (Hobbs, 2007) along with the role of demographic and psychosocial factors in internet users‘ perceptions of online activities. The findings of Gordon, Ramsay and Terras (2010) demonstrate a complex interrelationship, with the youngest internet users (16-24 years of age) both using and trusting social networking sites more than older age groups, but users with low self-esteem demonstrating significantly greater reliance upon the internet overall. The next phase of this research will be to examine the development of the ability to evaluate on-line content over the lifespan, and the ability to transfer this skill between domains of application such as education. In addition to specific individual differences educators must be aware that students may vary not only by age but also in terms of their computer literacy and media literacy skills. There has been much interest in the N-generation students (Barnes, Marateo and Ferris, 2007) or what Prensky (2001) calls ―digital natives‖, namely the generation(s) who have grown up with digital technologies such as the internet, online gaming, Nintendo WiiTM XBox TM, Blackberrys TM and iPods TM. Given their digital lifestyle, it is anticipated they may possess

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different media literacy skills from previous generations. However, the process of and the extent of transfer of such skills into educational contexts remains unclear. Greenfield (2009) argued that informal learning environments are producing learners with a new profile of cognitive skills. For example there is accumulating evidence that games players have better visual-spatial skills than non-games players (Green and Bavelier, 2006). These improved attentional and visual spatial skills may allow digital natives to cope with the fast paced world of continually changing stimuli and interactions that they inhabit in their leisure time. Playing computer games may also does support higher order thinking skills such as critical thinking, problem solving, complex decision making, argumentation and deduction and hypothesis testing (Dondlinger, 2007). Steinkuehler and Duncan (2009) provided evidence that the informal use of games can support higher level thinking, discussion and debate. They showed that players of the MMOG, World of Warcraft, frequently engage in high-level discussions and arguments in their online fora, demonstrating an impressive variety of higher order scientific reasoning skills, such as using data and argument, building on others‘ ideas and using system based reasoning. There has also been interest in the idea that playing computer games can support digital literacy skills in other ways. For example many modern entertainment games are structured around a narrative and it has been argued that playing games may help children to acquire an understanding of narrative structure, which is fundamental to success in reading and writing. In developing an educational game for learning history, Huizenga, Admiraal, Akkerman and ten Dam (2007) proposed that storification (narrative) might be a particularly good way to teach history as it might help the students to organise and structure historical knowledge which might otherwise appear fragmented. However Greenfield argues that these informal learning environments do not support more traditional academic skills, such as abstract vocabulary, reflection, critical thinking, and imagination which are better supported by older technology and reading. It is fair to say that we are in the very early days of studying the impact of new media on skill acquisition. While Greenfield argues that new media provide digital natives with new profiles of cognitive skills which are highly effective for dealing with new media, there is still a feeling especially amongst academics that the older skills are still of crucial importance. Despite their potential, the actual transfer of skills from social to educational context has so far been rather disappointing. Benett et al (2008) also cautions us to bear in mind the limitations of the skills of digital natives, these limitations are the key skills for media literacy and education. They are generally not skilled at locating and evaluating information. So although the potential for transfer is great, educators should not assume that it is automatic, it may need to be nurtured and encouraged in those who do posses it and taught to those who don‘t.

LEARNING, MOTIVATION AND THE APPEAL OF NEW TECHNOLOGY The learning potential of Web. 2 technology is widely recognised: ―Web 2.0 has the potential to provide students with learning experiences that are ―.. personally meaningful, collaborative, and socially relevant‖ (Greenhow, Robelia and Hughes, 2009, pg. 249) and there is much debate on how these learning experiences can be maximized. Although the

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supportive learning platform may be shifting from the classroom and books to the internet and online content, the fundamental issues that require explanation remain the same – How do we learn? How can learning be developed and supported? These issues lie at the core of psychological theory and research. Psychological theories have contributed not only to our understanding of learning but have also demonstrated how new technologies can support effective learning. Modern theories of effective learning propose that learning is most effective when it is active, situated, socially mediated, individualized and skills based (Woolfolk, 2007). New media provides many opportunities for active and situated learning through problem-based learning and Gee (2008) argues that active, situated learning allows games to support a new literacy which is highly consistent with how human beings learn. Social constructivist theories highlight the importance of social interaction in effective learning. Vygotsky‘s influential idea of the ―zone of proximal development‖ proposed that children learn best when they are tackling problems which are just beyond their current level of understanding and expertise with the assistance of a more experienced and able adult or peer to provide hints and guide their attempts at solution. These ideas are highly influential in e-learning, where many applications, including digital games, aim to support learners by providing maximally supportive feedback, such as tips or hints, to help learners progress to the next level. The use of Web.2 technology supports a move from passive to more active forms of learning. McLoughlin and Lee (2008) discuss the traditional application of Vygotskian and Constructivist principles within education and advocate the need to reconceptualise educational pedagogy with respect to opportunities afforded by Web.2 technology and the skills of the internet generation. Within the context of their proposed knowledge-construction paradigm Web.2 technology supports learning in two main ways (1) by providing access to existing information and (2) by allowing students to learn by actively creating and contributing to the existing knowledge-base. From a Psychological perspective Web.2 technology offers increased opportunities for active learner participation and creation and offers exposure to an immense socio-educational context that is built on premise of creating contributions and collaboration. Web.2 technology offers an immense range of rich and varied learning opportunities. In short it may represent a Constructivist‘s dream learning environment. The social nature of learning is evident in learning communities. Participating in networked media provides opportunities for collaborative learning through interaction with others. Many ―communities of practice‖ have been established where the knowledge, experiences and resources of potentially huge numbers of people are pooled via learning communities which focus on specific issues (Wenger, 1999). A well-known example is Mumsnet where mothers share information about childcare and other issues. This collaborative approach to learning is also evident in Massively Multiplayer Online Games (MMOGs) where players tackle highly complex and sophisticated problems by pooling their diverse expertise and resources. New models of learning also place a strong emphasis on skills and the links between knowledge and skills. In order to have a useful and usable knowledge-base, we need to have the skills to use that knowledge correctly. The importance of medial literacy skills is increasing reflected in effective learning policies in schools, such as the Scottish government‘s Curriculum for Excellence, and in Higher Education (such as the learning outcomes specified by Scottish Higher Education Funding Council) are very strongly skills

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based. Skills based curricula are highly relevant to the promotion of media literacy where there is a strong emphasis on the skill set required to use new media effectively. Good Media Literacy skills are essential if we are to maximise the educational potential of Web.2 technology. In fact, Leu et al (2009) go as far as proposing that the internet should be framed as a literacy issue as this is the most informative way to conceptualise the significance of media literacy skills and set the research agenda within education. If Web.2 technology is to support learning and education in a meaningful way then students must be skilled at accessing and understanding the unprecedented amount of information which the internet allows access to. Hyperlinks provide global access to massive amounts of information. However there have been concerns that the associative structure of the information presents a problem for how people use this knowledge. The internet stores information in an associative and inter-connected format. While critical thinking and judgment have always been features of literacy, these skills have become particularly important in dealing with information presented in this distributed manner. Effective media literacy entails not only the ability to access this information but also to evaluate it. Research examining internet search strategies offers some insight into the access of information. Guinee et al (2003) investigated the strategies that teenagers used when conducting internet searches and identified ―three approaches for locating information on the Internet, seven methods for constructing search strings, and four techniques for recovering from unsuccessful search attempts.‖ (pg.363). Internet searching and reading may also involve behaviours such as ―scanning‖, using visual aids such as images (Henry, 2006) and the nature of the website (liner or non-linear) may impact upon students‘ ability to recall information and to remember where the information was to be found and meta-cognitive ability influenced ability to recall information when using the non-linear website (Schwartz et al., 2004). Perfetti et al (2009) developed a model that represents the way in which internet users work with several sources at one time, in order to achieve their search goals. In summary, being ―media literate‖ taxes what is understood as a limited/finite set of cognitive resources. In order to support the effective use of new media in education a full understanding of the relative contribution of socio-psychological factors (e.g. self-esteem, working memory, motivation and emotion) and socio-technological factors (e.g. usability, user experience and web design) is required. Psychological theories have an important role to play in explaining the engagement offered by new media, while theories of learning developed by psychologists can also help us to explore the most effective use of new media in an educational context. Theories of cognition can help us think about the skills and strategies used in media literacy and may help inform our understanding of factors that support the transfer of media literacy skills from social media (e.g. social networking, blogging, computer gaming) to educational contexts (e.g. virtual seminars). It is clear that new media provide hugely enjoyable leisure experiences and Psychological theories offer interesting insights into the motivational appeal of new media. Many individuals spending large quantities of their leisure time online, using social networking sites, playing games, shopping, gambling etc. For example Scottish students play computer games an average of 7 hours per week with one third of males playing for more than 6-10 hours per week (Connolly, Boyle and Hainey, 2007). Similar results have been reported in the USA (Lucas and Sherry, 2004) and Taiwan (Chou and Tsai, 2007). In trying to explain the nature of the appeal of new media, constructs such as flow (Csíkszentmihályi, 1990; Sweetser and Wyeth, 2005), immersion (Jennett, Cox, Cairns, Dhoparee, Epps, Tijs and Walton (2008)

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and presence (Weibel, Wissmath, Habegger, Steiner, & Groner, 2008) have been proposed. Flow describes the immediate, rewarding, subjective, emotional state of optimal pleasure that arises when individuals are absorbed in favoured activities. For flow to occur there should be an optimal match between the skills an individual possesses and the challenges presented by the activity; the activity should also be immersive and require concentration and a sense of personal control. There is evidence that flow is experienced in using media (Sherry, 2004) the internet (Chen, 2006) and in playing games (Hsu and Lu, 2004). Recently, concerns have been voiced that excessive internet use could easily develop into an addiction (Young, 1998; Parker, Taylor, Eastabrook, Schell, & Wood, 2008). Lee and Larose (2007) found that many players slip into habitual online game playing because they find it difficult to regulate the amount of time that they spend playing online games. It seems that one of the digital literacy skills that we may need to teach N-gen students is to regulate their behaviour online. Psychologists have developed a wealth of knowledge in the area of addictions and it seems likely that this knowledge will have relevance in understanding internet and game addiction.

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CONCLUSION In this chapter we have argued for a psychologically informed conceptualisation of media literacy and increased recognition of the valuable contributions that can be derived from Psychological theory and research. This lack of explicit appreciation is all the more surprising given the historical contribution that Psychology has made to the characterisation and comprehension of numerous applied problems in educational and technological contexts. Through the use of examples, albeit a restricted set given limitations on the scope and word length of this paper, we have shown how psychology has and can shape our understanding of the application and implications of new media. We hope readers will begin to appreciate the advantages that can be gained by considering the psychological dimension of media literacy. We advocate that a detailed consideration of the insights offered by Psychological research is a constructive way to progress our understanding of media literacy. We recommend an increased recognition of Psychological factors and the adoption of a multidisciplinary approach to media literacy. Such an approach not only offers exciting new opportunities for the development of our understanding of media literacy skills and educational pedagogy, but also in turn offers significant challenges to current Psychological theories. As Psychological research attempts to explain behaviour in the increasingly rich virtual environment, reassessment and revision of current theories and understanding will be required; these new insights will then inform research and subsequent interventions. Whilst embracing the development of new theories and research methods such as virtual ethnography (Hine, 2000) to explore the internet, we also encourage the recognition of existing theory, and how existing theory and research can be applied and developed to help understand behaviour in the digital age. By their very nature, interdisciplinary perspectives are complex, and even more so given the constantly developing applications and uses of technology. Consideration of the Psychological dimensions of media literacy also presents challenges to Psychologists themselves, as they work to understand human behaviour in the digital age. Just as educationalists advocate the need to reconceptualise learning and education in the

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digital environment, Psychology researchers are addressing novel behaviours in on-line contexts. If Psychology aims to characterise, understand and explain behaviour, then a major objective of Psychology in the 21st century will be the study of behaviour in the ever expanding and increasing important virtual environment in which individuals are spending increasingly large portions of their lives. This yields a new and exciting challenge for Psychologists both in terms of theory and methodology, and many are already rising to meet this challenge. Some of the issues that need to be considered are: How well can existing theories explain newly emergent behaviours in virtual environments? Do humans develop new skills and learning styles when operating in on-line contexts? To what extent can existing views of reading be applied to reading online? Can traditional psychological explanations of social interaction be applied to help us understand social networking and related online pursuits such as on-line dating? New communication media and the literacy skills required raise questions about the benchmarks of literacy. Just because it is different and many educators may struggle to understand or even appreciate this genre, does it actually make it deficient? Whilst there is a very considerable amount of demographic information about potentially excluded populations, the war will be won through harnessing and understanding of the Psychological aspects that may lead to exclusion the barriers and enablers of media literacy. Like new interactive media itself, our understanding of it and the challenges and opportunities presented is constantly evolving. In order to fully appreciate the social and educational significance of technology we need to appreciate the ecological and transactional nature of the relationships between individuals and how they cope, adapt and interact with technology to meet their needs. Psychology has a long history of advocating an Ecological perspective to development (e.g. Bronfenbrenner, 1979) and it is interesting to note that Greenhow et al (2009) similarly advocate a ―learning ecology perspective‖ to conceptualise education and bridge the gap between learning and teaching across home, educational, work and virtual contexts. Only by studying behaviour across all these contexts will we develop a holistic and nuanced understanding of the skills that are necessary for effective participation. As a discipline with the objective of understanding behaviour, the consideration of the Psychological dimension is crucial for both education and society.

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Henry, L. A. (2006). What reading demands does searching on the Internet require? A review of the literature. National Reading Conference, Los Angeles, California, USA. Accessed on 19th February 2010 from http://www.newliteraciesuconn.edu/eventfiles /NRC2006_NBS_handout.pdf Hine, C. (2000). Virtual Ethnography. London: Sage. Hsu, C-L, & Lu, H-P, (2004). Why do people play on-line games? An extended TAM with social influences and flow experience. Information and Management, 41, 853-868. Huizenga, J., Admiraal, W., Akkerman, S. and Dam, G. ten (2007). Learning History by playing a mobile city game. In Proceedings of the 1st European Conference on GameBased Learning (ECGBL). October 2007, University of Paisley, Paisley, Scotland, 127134. Jennett, C., Cox, A. L., Cairns, P., Dhoparee, S., Epps, A., Tijs, T. & Walton, A. (2008). Measuring and the experience of immersion in games. International Journal of HumanComputer Studies, 66(9), 641-661. Johnson-Laird, P. N. (1983). Mental models: Towards a cognitive science of language, inference, and consciousness. Cambridge, MA: Harvard University Press. Kim, E. J., Namkoong. K., Ku. T. & Kim, S. J. (2008). The relationship between online game addiction and aggression, self-control and narcissistic personality traits. European Psychiatry, 23, 212-218. Lee, D. & LaRose, R. (2007). A socio-cognitive model of video game usage. Journal of Broadcasting & Electronic Media. 51(4), 632-650. Leu, D. J., O‘Byrne, W. I., Zawilinski, L., McVerry, J. G. & Everett-Cacopardo, H. (2009). Comments on Greenhow, Robelia, and Hughes. Expanding the New Literacies Conversation. Educational Researcher, 38(4), 264-269. Lucas, K. & Sherry, J. L. (2004). Sex differences in video game play: A communicationbased explanation. Communication Research, 31(5), 499-523. McLoughlin, C., & Lee, M. (2008). Future learning landscapes: Transforming pedagogy through social software [Electronic version].Innovate, 4. Retrieved 15 February, from http://www innovateonline.info/index.php?view=article&id=539 Minsky, B. D. & Marin, D. B. (1999). Why faculty members use email: The role of individual differences in channel choice. The Journal of Business Communication, 36, 194-217. Ofcom (2009). Report of the Digital Britain Media Literacy working group, 27 March 2009. Accessed 25 January 2010 at http://www.ofcom.org.uk/advice/ medialiteracy/media litdigital_britain/ Perfetti, C. A., Rouet, J.-F.& Britt, M. A. (1999). Toward a theory of documents representation. In H. V. Oostendorp and S. R. Goldman (Eds.), The construction of mental representations during reading. Mahwah, NJ: Erlbaum. Prensky, M. (2001). Digital game based learning. McGraw-Hill. Rosenberg, M. (1965). Society and the adolescent self-image. Princeton, NJ: Princeton University Press. Rotter, J. B. (1966). Generalized expectancies for internal versus external control of reinforcement. Psychological Monographs, 33, 300–303. Schwartz, N. H, Andersen, C, Hong, N, Howards, B. & McGee, S. (2004). The influence of metacognitive skills on learners‘ memory of information in a hypermedia environment. Journal of Educational Computing Research, 31(1), 77-93.

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Steinkuehler, C. & Duncan, S. (2009). Informal scientific reasoning in online virtual worlds, Journal of Science Education and Technology, DOI: 10.1007/s10956-0089120-8. Sweetser, P. & Wyeth, P. (2005). GameFlow: a Model for evaluating player enjoyment. ACM Computers in Entertainment, 3(3), 1-24. Weibel, D., Wissmath, B., Habegger, S., Steiner, Y. & Groner, R. (2008). Playing online games against computer-vs. human-controlled opponents: Effects on presence, flow, and enjoyment. Computers in Human Behavior, 24(5), 2274-2291. Wenger, E. (1999). Communities of Practice. Learning, meaning and identity. Cambridge: Cambridge University Press. Wharton, C, Rieman, J, Lewis, C. & Polson, P. (1994). The Cognitive Walkthrough: A practitioner's guide. In Nielsen, J. and Mack, R. L. (Eds.), Usability Inspection Methods. John Wiley and Sons, Inc. Woolfolk, A. (2007). Educational Psychology, 10th edition. Boston, MA: Pearson International Edition. Young, K. (1998). Caught in the Net: How to Recognize the Signs of Internet Addiction – and a Winning Strategy for Recovery. New York: John Wiley. Young, R. M., Green, T. R. G., & Simon, T. (1989). Programmable user models for predictive evaluation of interface designs. In Proceedings of Conference on Human Factors in Computing Systems, 15–19. ACM.

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Chapter 6

INVESTIGATION OF NEW EDUCATION METHODS USING APPLIED MECHATRONICS Sezgin Ersoy Marmara University Technology Faculty Mechatronics Department Istanbul Turkey

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ABSTRACT Mechatronics is an area that merges multidisciplinary knowledge coming from mechanical engineering, electronics and computer technology. Vocational training in mechatronics requires the teaching of ―multi-skills‖ and ―multi-intelligent‖ in various learning contexts, as well as a good blend of learning in the classroom and practical training in schools where is steered with quality management system. Quality education is the education in which the provider offers education services in accordance with certain standards, develops skills, attitudes that enable a person to accede to a higher stage of career development, self discovery, personality development, adaptability to labor market and life long learning. Quality in education must be defined not only on the basis of what is needed now for an adult or a young person but depending on how it manages to meet future needs. A quality education is not only to ensure progress in achieving predetermined objectives, but also to set new trends and new ways of achieving them. Vocational training colleges together with industry are confronted with the need to develop and integrate theoretical and practical learning sequences that are able to fulfill the demands for multi-skilled technicians and skilled workers. The claim for work-related learning based on the interleaving of theoretical learning and learning by practical work and experimentation is obvious [1] A major goal in mechatronics training is that students have to acquire theoretical and operational knowledge and practical competencies in terms of technical core skills. This type of skills generally relates to the assembly and service of complex machines, plants and systems, in the field of plant construction and mechanical engineering, and in those companies that purchase and operate such mechatronic systems. It describes the effect of some learning methods that apply quality management in an organized educational environment and system. Mechatronics is an interdisciplinary science, so we have to use different learning methods according to the curricula‘s specific

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target. The main aim of this paper is to increase the learning levels of mechatronics education in order to have and efficient assessment [2].

1. MECHATRONICS

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Mechatronics, the popular science of our century, is an interdisciplinary perception which grows out of the combination of machine, electric-electronic and software technology in the process of planning to production. Mechatronics which is in fact shortly expressed as ‗interdisciplinary‘ is a synergism which is formed by technical and physical sciences. Mechatronics: It is the field of implementation which is realized in an interdisciplinary and equal-aimed structure of computer technology. Mechatronics products aim to produce smart machines, devices and systems that make human life easier [3].

Van Amerongen, 2006. Figure 1. Mechatronic engineers versus conventional mono-disciplinary EE‘s and ME‘s.

The human profile that the society of our present-day needs is different from the human profile that the society of the past-times needs. The globalization occurred due to the improvements in science and technology and the basic components that identify the human force profile which is required by info-based society. The discussions about the quality and quantity of education began to take place and the re-construction in education is put on the agenda. Now the teacher has no control over knowledge. The core problem is the student. To truly have the student in the centre of teaching approach, the teacher must be prepared to exercise much more nuanced role than before. The teacher‘s success during its classes

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depends on the learning opportunities he creates for each student. Thus, depending on context, the teacher always acts, but adequate and in custom with the group needs. In the period of 2000s, the students‘ and the teachers‘ being able to gain new skills depends highly on their being able to use the technology. Because technology is a means of reaching, using, producing and sharing data. The most important means to enable us to reach the data is computers. The use of computers is becoming increasingly important in today‘s societies. [3] By considering these things, the educational institutions began work and implementation in order to make the students gain computer skills.

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1.1. Mechatronics Approach The most valuable resource of a society that enables it to survive is human power. The education and employment of this resource not only shows the difference of a society from the others, but renders a healthy interaction within the society. This difference is only possible with education. There is yet no consensus about the concept of education. There are different definitions of education [4]. A quality education requires the use of active-participating methods which remove the students from the training objects and turn them into active subjects, co-participants in their own training. Put in the position of young researchers, students like to rediscover the truths of science. Also, an important role play the partnerships with companies, in which students can carry hours of practice, thus directly connected to reality. There they may see products made by them and the importance of ownership by those products of quality standards in order to be placed on the market. When we look at education within this framework, the factor which will provide the biggest contribution to the development of the country is the vocational, technical education. The vocational, technical education must serve the society more and more every single day in order to provide for the limitless needs of humans. [5] Although the fact that vocational, technical education should not ultimately educate people into only one unique mold does not seem to agree to the other concepts of education, vocational improvement will only be possible with the employee who has acquired good vocational background, who can speculate the future and who can present his/her speculation with scientific research. These qualifications are only possible when the individual gets a good vocational education. To prepare human beings for a world more and more complex means giving them a chance to somehow find themselves in this world. For this teachers must find the most appropriate ways to address to different content, create access to content, the last one being ultimately the way to cope with complexity of the world and current culture.

2. EDUCATION 2.1. Education Framework The quality of education is measured with the quality of thee students who are educated by educational institutions. Quality of services of an educational organization is proven by the quality of graduates, their ability to integrate into society (in working groups, in interest

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groups), their ability to handle a job and, especially, to keep this place for work responding to the employer requests proving possession of skills required by job description, communication and adaptation abilities, reaction skills in crisis situations, involvement in the life of the organization, accountability, power to make decisions and correct self-assessment science. All this depend on teachers, the education program and the suitable environment. Among these elements the teacher is the most important for the education to achieve the desired aim. Therefore, the teacher is one of the basic elements in our educational system. Rendering the educational system effective; in other words, educating the necessary human power at the optimum level is only possible by continuously observing the teacher-training system and by solving the problems and improving the system. [6] Williams and Alawiye (2001), had a pilot application program which they called Professional Partnership Program. At the end of the program they observed that it had been a wonderful experience both for the teachers and students of the school; and the primary school students had greatly benefited the teacher candidate‘s enthusiasm and knowledge [7]. Brandon (2000) compared the effect of the teaching application of the teacher candidates, who were second year students, according to the gender variable and found that while the effect of certain teaching qualifications were lower in female candidates before the teaching (application), no difference was found between the genders in skills in teaching (application).[8] Cambers and Roper (2000), had a study in which the reasons of the dropouts from a oneyear teacher program to become a teacher in an English middle school were asked, some students found the school where they were for training was not only helpful but preventive and the teachers there were also unhelpful. [9] It was determined that the reason for their dropping out was the work load, stress, low morale and general unhappiness. Girod and Cavanaugh (2001) considered technology as the agent of change and they suggested the teachers be provided with time, support and creative space to use technology. [10] Halbach (2000) concluded that the teaching application in class was much more effective on the students‘ viewpoint than what was taught. [11] Lee, Chi and Walker (2000) observed that many teacher candidates had negative beliefs about the school management [12]; however, the candidates said they did not expect any change in power relationship although they were not happy about the status quo. [13]

3. LEARNING METHODS 3.1. Active Learning Active learning becomes one of the methods that can be used in every branch of education. Active learning presented as an education technology that includes education sets as a teaching material in classrooms and software belonging to these sets with animations that are used in automotive technologies education, simulation , etc,. Main purposes of using Information Technologies (IT) in education are [14]:  

Increasing the quantity and the level of learning Reducing the time that students spent to reach their target.

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 Increasing the efficiency of teaching staff  Reducing the cost of education with non-decreasing quantity According to Robert and Simon Active learning is a process that learners can have opportunities to make decisions about special features of learning process and they are forced to use their intellectual abilities during learning [15]. There are some requirements for Active learning. These are:

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1. How to learn information, how to use time. 2. Information is a concept that can be reached by discovering. Learning technologies like analyze, synthesis, discussion, questionnaire should be used to reach information. 3. Students learn more efficiently in social environments. Learning is a personal and internal process and social interaction increase effectiveness of this process. It determined that when students were aware of their own behaviors when they learned strategically or not. To provide student success and educational success in long term, technology has to be used in the direction of new teaching philosophy and in new scenarios with definitions of new roles instead of using it in traditional education scenarios. [16] Behaviorism is a psychological theory that opposes structuralism and functionalism. It defends the idea that observation of the attitudes and situations can be seen through eyes, not the conscious situations. According to behaviorists, the only thing that can be observed by objective techniques is environmental stimulants and the reactions of people to these stimulants. In traditional education, teachers decide what students will learn, when and how they will do so. They teach students on a process in which they are passive and quiet. After this, in exams they demand students to repeat what they have been taught. They assume that students can learn in the same way as their teaching form. The table that is generated by Johnson and Smith (1991) to show the differences between Active learning and traditional education is presented below for the Automotive Mechatronics lesson. Active Learning Method is applied on Mechatronics class and it is seen that this method has a positive effect on academic success in comparison with traditional method. The effect of Active Learning to knowledge stability is measured. When we observe the results, we can see that the success of students is higher in After test and it is less in Stability test. The effect of all information that is learned in stability of mind causes behavioral difference of information that is damped in time. By being applied in Mechatronics Education; Active Learning can have students gain the abilities like recognizing target information, analyzing, finding alternatives on regression and solution. Moreover, Active Learning improves the student‘s will to learn technical information and adaptation in team work.

3.2. Problem Based Education Problem based learning and teamwork activities often turn out to be the student's first point of contact with what Industry is really like and becomes a fundamental milestone in

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their learning throughout their degree course. The complete development of products and machines provides opportunities for active learning projects where students can apply computer aided design, engineering and manufacturing technologies, as well as the most advanced rapid prototyping technologies, so highly valued by Industry. [17] Undertaking problem-based learning and teamwork activities where students can experience the complete development of a product or machine, following the stages used in the industrial world, brings them closer to future work experiences. Aspects, such as active decision-making, weighing up alternatives, self-teaching, time and cost planning, the application of regulations, design in line with commercial elements or contact with suppliers, are given an enormous boost. [17] In multi-disciplinary systems like Mechatronics, solving problems need evaluation with a wide-perspective. Defining the problem yields the necessary point of view for the right approach to the solution.

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Table.1. Active Learning Methods for Mechatronics Education UNIT

CLASSICAL METHOD

Information

Books and teachers present the subject, explain and show an implementation.

Students

It is an empty tool that will be filled up by teachers.*

Purpose of the teacher

Separate and classify information and implement them.*

Relationships

There is no personal relationship between student and teacher*

Context

Competitor and individual *

Assumptions

Every expert can teach.*

ACTIVE LEARNING Visual and written documentations and a CD of animations, documentations and films prepared before were given to students. Besides being active, creative, finder, converter to his/her own information, students can define parameters like working with a group, sharing knowledge and organize practice time. Developing the abilities of students and sufficiency and guidance. It is in the position that gives information when needed. Student always has a communication and interaction with teacher. Teacher leads about acquiring information and how to use it. Cooperation in education environment.* Teaching is complicated. Individual characteristics and acquiring are directly affected on learning. Learning and teaching processes should be checked in time.

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3.3. Web-Based Education Education and teaching aimed data‘s transference to the required place electronically by means of communication instruments such as radio, television, computer, internet and similar items is called ‗e-learning‘. Even the instructor and the student are in different places, the transference of information and teaching function is fulfilled by means of communication technology. Shortly, e-learning eliminates the difficulties of distance and participation. The Internet and web offer a number of advantages over other computer-based approaches to distance learning that do not use wide area networks. Here are some of them:

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1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Resource management Student/user management Time/place flexibility Currency Ease of use. Cross platform compatibility Accessibility Customization Resource leveraging/enrichment Resource integration Collaboration Dual use Duplication and other distribution costs Productivity

E-Learning and the Improvement of E-Learning Materials For the teachers‘ being able to gain the skills to prepare effective teaching materials, they need to know very well the functions of these materials in teaching environment, the principles that they need to consider at the stage of preparation, the benefits and limits of commonly used materials and the features that needs to be considered when they choose and use these materials. When they know these things not in only information level but also in implementation and evaluation level, it will be helpful for these teachers to develop materials in their future lives. It‘s shown Figure.2 below the way followed in combining technology and lessons for the education of teacher candidates. [18] In order to increase the quality of education and teaching, the effective use of modern teaching technology in teaching of concepts is becoming more important day by day. In that case, one of the most important advantages of the use of computers in teaching environments is its increasing the degree of learning by appealing to a lot of sense organs at the same time and make what‘s learnt more permanent. Because of that reason, it is pointed out that the use of animations, pictures and sound at the same time eliminates the conventionalism of teaching environment and increases the degree of learning [19].

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Candidate Teacher Culture Knowledge

Course Knowledge

Teaching Knowledge

Education Technology and Material Developing Culture Knowledge

Course Knowledge

Teaching Knowledge

Well-qualified Teacher Figure 2. Process of ―education technology and material developing‖ course in Education Faculty.

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On the other hand, technology-based teaching materials are extremely needed in order to construct teaching environment for the students who come from different social environments and who are physically, biologically and cognitively different from each other .However, the students‘ having different cognitive, perceptional qualities and physcomotor skills makes it more difficult for teaching technologies to improve by considering individual differences. Because of that, it is emphasized that there is no technology to make it possible that a topic is learnt by all the students at the same degree and at the same speed. [19].

3.4. Project Based Education Project Based Learning is an instructional approach built upon authentic learning that engage student interest and motivation. These activities are designed to answer a question or solve a problem and generally reflect the types of learning and work people do in the everyday world outside the classroom. Project Based Learning is synonymous with learning in depth. A well-designed project provokes students to encounter (and struggle with) the central concepts and principles of a discipline. Project Based Learning teaches students 21 st century skills as well as content. These skills include communication and presentation skills, organization and time management skills, research and inquiry skills, self-assessment and reflection skills, and group participation and leadership skills. Project Based Learning is generally done by groups of students working together toward a common goal. Performance is assessed on an individual basis, and takes into account the quality of the product produced, the depth of content understanding demonstrated, and the contributions made to the ongoing process of project realization.

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Finally, Project Based Learning allows students to reflect upon their own ideas and opinions, exercise voice and choice, and make decisions that affect project outcomes and the learning process in general. [20] Combining these considerations, we define Project Based Learning as: a systematic teaching method that engages students in learning essential knowledge and life-enhancing skills through an extended, student-influenced inquiry process structured around complex, authentic questions and carefully designed products and tasks.

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Characteristics of Authentic Learning Activities 1. Real-world relevance: Activities match as nearly as possible the real-world tasks of professionals in practice rather than decontextualized or classroom-based tasks. 2. Ill-defined: Activities require students to define the tasks and subtasks needed to complete the activity. 3. Complex, sustained tasks: Activities are completed in days, weeks, and months rather than minutes or hours. They require significant investment of time and intellectual resources. 4. Multiple perspectives: Provides the opportunity for students to examine the task from different perspectives using a variety of resources, and separate relevant from irrelevant information. 5. Collaborative: Collaboration is integral and required for task completion. 6. Value laden: Provide the opportunity to reflect and involve students‘ beliefs and values. 7. Interdisciplinary: Activities encourage interdisciplinary perspectives and enable learners to play diverse roles and build expertise that is applicable beyond a single well-defined field or domain. 8. Authentically assessed: Assessment is seamlessly integrated with learning in a manner that reflects how quality is judged in the real world. 9. Authentic products: Authentic activities create polished products valuable in their own right rather than as preparation for something else. 10. Multiple possible outcomes: Activities allow a range and diversity of outcomes open to multiple solutions of an original nature, rather than a single correct response obtained by the application of predefined rules and procedures. [21]

3.5. Computer Based Education To be successful in modern organizations graduates need a strong combination of technical, academic, personal, and organizational skills. Integrated Technology Concepts (ITC) helps high schools teach these skills through a curriculum that combines project-based learning with the enterprise process. Amatrol's technology education program also motivates students to learn more because its project-based design engages students‘ natural curiosity. ITC students become active learners, taking charge of their own learning. [22].

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4. STRATEGICAL INDIVIUAL COMPENTENCIES

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New approaches to today's industrial needs has revealed that this approach is the result of mechatronics. Labor supply machinery, electronics, control, in areas such as automotive and robotics are met by trained persons. These people are technical and vocational education adapted to their interdisipline. In the process, technological equipment and environmental interactions are kept in the foreground. But this does not have enough human-human interaction and human environment interactions are inevitable. Labor market will be located in the nature of the individual described in the social, psychological features is important. Where the environment and workforce that can create, manage, and the results will be equipped with skills are needed to evaluate the technical elements of that strategic competence and leadership qualities can be explained by the individual.

Figure 4. Mechatronics Education aims on individual competencies.

Especially in the field of production and technology to develop common ground and common goals to create an environment can be implemented in the provincial competition is associated. Technical needs are met in the field grown in this area depends on the ability of individuals and production management. Technology in the field of vocational and technical education that individuals receive information and organize it according to the changing conditions of competition and technology can. However, this ability of individuals in this field of education is not enough to win. Because only the professional skills and technical staff to work in cooperation with well and results-oriented work may show activity. Strategic thinking and behavior the products of this kind of leadership qualities as a result unable to show the positive impact that might be do not know. These capabilities, as well as the environment - they can manage their individual and community relations skills and ideas as the product of the design process and should be able to Express. Vocational and technical

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education and manpower to manage the process of individuals and to give direction features contribute to the social aspects of communication of thought and behavior is essential. Personal skills training system in technical fields that are formatted and have been forwarded in the form of creation. Determining the ability of strategic thinking or not focus on the development. A technology research and development activity in the field only significance is given. The current situation in vocational and technical areas of the workforce developed leadership qualities and generation product development capabilities are thought to directly influence. This development will play a key role in the development of technology. Targeted at four groups of the adaptation and dissemination of this method is considered.

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Figure 5. Institutional Structure Of Mechatronic Education.

1. Universities: Universities will be transferred to an academic infrastructure yen depending on the needs identified in the adaptation, application and development process to create and evaluate. 2. Secondary Education Institutions: Technology in the field of manpower training in secondary education institutions as the basis of methodology, implementation and dissemination. 3. Speciall Organizations / Associations: Country to perform in practice, to observe and to inform the various institutions, commercial companies in the field of production and technology to promote workforce, the impact on education quality and results of the investigation to be available. 4. Commercial Experience: This application for organizations involved in field work and evaluation of policy implementation (pilot study) and the training results for the industrial environment, to prepare the return observation.

5. CONCLUSION Mechatronics Education is a science which should renew himself ahead the developing technology and industrial requirements. Integrating the technological developments with education, needs demonstrating the development in education subject and material as well.

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Though in theoretical lessons, presentation and content may important; in practical lessons, education should have team work, self-learning, live-learning goals. While comparing the education methods; the cognitive and attitude change which occurs in the trainee‘s behaviors; more than the information passed. Besides; Mechatronic trainees‘ Self-Strategic-Idea should be promoted for their presence in this multi-disciplinary field.

REFERENCES [1]

[2] [3]

[4] [5]

[6]

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[7]

[8] [9] [10] [11] [12]

[13] [14]

Attwell, G., Jennes A., Tomassini, M. (1997): Workrelated knowledge and work process knowledge. In: A.Brown (ed): Promoting vocational education and training: European perspectives, Tampere: University of Tampere Press 1997. Iosifescu, S. (coordinator): Quality management and culture in the schools, Bucharest, Romania 2005. Ersoy S., Görgülü S.; "C.B.E. and Progress Alternative Against High Costed Material for Mechatronic Education"; FISER'09 Frontiers in Science Education Research An international conference on science and mathematics education research;2009; North Cyprus. Prof.Dr. M. Kepçeoğlu; Psychology Consulty and Guidng; Istanbul; 1997, p.33. Ersoy S.; ―Defining Of Conceptions Related To Their Department Of Candidate Teacher of Mechatronics Education‖; Procedia Social and Behavioral Sciences; (18770428); Volume 1; Issue 1; 2117 - 2125; 2009 Battal N., and others ; ―Farklı Branşlardan Mezun Olan Sınıf Öğretmenlerinin Öğretmenlik Mesleğine işkin Görüşleri Ve Karşılaştıkları Sorunlar‖ Balıkesir Universty Social Science Institu Journal Volume: 1 Issue: 2. Williams, H. S. and Alawiye, O. (2001). ―Assessment: Lessons Learned From A Year Long Undergraduate Teacher Education Pilot Program.‖; Journal of Instructional Psychology, 28 (4), p:229. Brandon, D. P. (2000). ―Self-Efficacy:Gender Differences Of Prospective Primary Teachers �n Bostwana‖. Research in Education, p:64 (36). Cambers, G. N. and Roper, T. (2000). ―Why Students Withdraw From �nitial Teacher Training.‖ Journal of Education for Teaching, 26(1), p:25. Girod, M. and Cavanaugh, S. (2001). Technology as an agent of change in teacher practice. T H E Journal, 28 (9), p:40. Halbach, A. (2000). Trainee chane through teacher training: a case study in training English language teachers in Spain. Journal of Education for Tecahing, 26 (2), p:139. Lee, K., Chi, J. and Walker, A. (2000). Pre-service primary teachers‘s perceptions about principals in Hong Kong: implications for teacher and principal education. AsiaPacific Jounal of Teacher Education, p:28(1), 53. Aksu M. B., Demirtağ H.; ―Öğretmen Adaylarının Okul Deneyimi II Dersine İlişkin Görüşleri‖; Education Faculity Faculity Journal; Volume: 7 Issue:11 Spring 2006. Ari, M.; ―Mesleki ve Teknik Eğitimde Uygulanacak Uzaktan Eğitim Modelinde Laboratuvar Kullanımı ve Altyapı Ihtiyaçları‖; Ankara Üniversity – IVETA National Confreance, 2003

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[15] Robert, P.J. Simons, Definitions And Theories of Active Learning. Published: Huber, G.(Ed.) Active Learning for Students and Teachers, OECD Published, ss.18-36. [16] Ruth Garner, Patricia A. Alexander, Mark G. Gillingham, Jonna M. Kulikowich, Rachel Brown; American Educational Research Journal, Vol. 28, No. 3, pp. 643-659; 1991. [17] Yustos H.L., Lafont P., Lantada A. and others; ―Towards complete product development teaching employing combined CAD-CAM-CAE Technologies‖ Computer Applications in Engineering Education; Volume 17 Issue 3 p241 – 252; Madrid, 2009. [18] Gunduz And Odabasi,;―Bilgi Çağında Öğretmen Adaylarının Eğitiminde Öğretim Teknolojileri ve Materyal Geliştirme Dersinin Önemi‖, The Turkish Online Journal of Educational Technology - TOJET January 2004 ISSN: 1303-6521 Volume 3, Issue 1, Article 7. [19] [19] Saka A.Z., Yılmaz M. ―Bilgisayar Destekli Fizik Öğretiminde Çalışma Yapraklarına Dayalı Materyal Geliştirme Ve Uygulama‖, The Turkish Online Journal of Educational Technology - TOJET July 2005 ISSN: 1303-6521 Volume 4, Issue 3, Article 17 [20] (http://pbl-online.org/ Erişim tarihi 02.12.2009) [21] Nedic, Z., Machotka, J., Nafalski, A.: Remote Laboratories Versus Virtual and Real Laboratories. In: 33rd ASEE/IEEE Frontiers in Education Conference T3E-1 (2003).

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In: Science Education in a Rapidly Changing World Editor: Seth D. Grahame

ISBN 978-1-61728-914-9 © 2011 Nova Science Publishers, Inc.

Chapter 7

DEFINITIONS AND SIGNIFICANCE OF EPISTEMOLOGICAL BELIEFS AND BELIEF ABOUT THE NATURE OF SCIENCE IN RELATION WITH SCIENTIFIC LITERACY Esra Macaroglu Akgul

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Yeditepe University

Knowing what science is, how scientific knowledge is produced, what limitations does this knowledge has, who is a scientist and how does scientist work, in other words, understanding the nature of science corresponds to individuals‘ scientific literacy (Macaroglu, 1999). World-wide research shows that many people are not well informed about science. Therefore; scientific literacy is one of the emphases cited in science education programs throughout the world. The major limitations in scientific literacy can be attributed to many factors. One of the important factors cited in the literature is the knowledge of science and science teaching pedagogy of elementary school teachers. Therefore, there is a need to study elementary school teachers‘ knowledge of science and science teaching pedagogy. Isenberg (1990, p.322) describes three assumptions in which educational research studies with teachers are based on.   

Teacher‘s practice is under the effect of her thoughts. Thoughts, decisions and judgments lead teaching process. Teaching is a decision making process at very high levels.

Based on these assumptions; one might conclude that teachers‘ epistemological beliefs, which include their understandings about the nature of science, effect their decision making and execution process. Perry (1981) defined epistemological belief as ―someone‘s point of views on the definition and sources of knowledge, the degree of its certainty, and its limitations and criteria‖ (Brownlee, 2001). Schommer (1993) describes beliefs about the nature of knowledge and the nature of learning as epistemological beliefs as well as Jehng (1993) identifies epistemological beliefs as socially shared intuitions. Meta-cognition is based

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on individuals‘ knowledge about their own strategies to learn and to construct meaning. In contrast with meta-cognition, epistemological beliefs are basic assumptions about the limitations and criteria of knowing. Additionally, these beliefs include the sources and conditions of knowledge production (Bauer, 2004). The number of educational research studies on learners‘ beliefs about the nature of learning and knowledge is increasing (Chan and Eliot, 2004). Definitions of learners‘ related beliefs and examinations of how these beliefs would reflect on individuals‘ interpretations about their own learning are the basic foundations in the related literature (Clarebout 2001, p.53). As someone‘s‘ epistemological beliefs include the nature of knowledge, one‘s beliefs about the nature of scientific knowledge can be also counted as this individual‘s epistemological belief. It is necessary to study elementary school science teachers‘ understandings in their school years. This chapter will include a research study with prospective elementary science teachers. In the research study; prospective elementary science teachers‘ developing understanding of science teaching pedagogy and ―beliefs about the nature of science‖ are examined. The question of ―How their epistemological beliefs influence their practice teaching?‖ is also addressed in the research. Here, in a historical context, we need to define each concept individually.

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SCIENTIFIC LITERACY Although scientific literacy is the major theme of current reform documents in different countries including Turkey, there is no consensus on the definition of scientific literacy. The following pages include a brief historical summary of the definitions made by different people and organizations. Some educational researchers have a tendency to define scientific literacy in relation to language literacy. Koch and Eckstein (1995) emphasized that scientific literacy requires an active and critical engagement of the reader in the interpretation of the meaning of a science text. A scientifically literate person should take a critical stance toward science texts and develop the ability to interpret them from a theoretical perspective (Koch, & Eckstein, 1995). Sutman (1996) made a similar connection between language literacy and scientific literacy in his definition of scientific literacy. Sutman (1996) argues that scientific literacy is not dependent upon any specific science content or process knowledge. Scientific literacy consists of the abilities and willingness to continue to learn science content, to develop science processes on one‘s own and to communicate the results of this learning to others. In contrast to Sutman, Mayer (1997) argues that scientific literacy is depended upon specific amount of science content knowledge. Mayer (1997) defines scientific literacy as the knowledge of the substantive content of science that is related specifically to understanding the interrelationships among people and how their activities influence the world around them (Mayer, 1997). Reform efforts in the United States brought another definition of scientific literacy. American Association for the Advancement of Science - AAAS (1990) designed Project 2061 and defined scientific literacy as ―the ability to use scientific knowledge and ways of thinking for personal and social purposes. According to this definition cited in Project 2061; scientific literacy has many facets. These include being familiar with the natural world and respecting its unity; being aware of some of the important ways in which mathematics, technology, and

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the science depends upon one another; understanding some of key concepts and principles of science; having a capacity for scientific ways of thinking; knowing that science, mathematics and technology are human enterprises, and knowing what that implies about their strengths and limitation (American Association for the Advancement of Science, 1990, pp.xvii-xviii). The National Science Education Standards in US define scientific literacy as ―the knowledge and understanding of scientific concepts and processes required for personal decision making, participation in civic and cultural affairs and economic productivity‖ (National Research Council, 1996, p.22). Parallel to the science education reform taking place in the United States, there were some international efforts in Europe as well as in other parts of the world. The Royal Society in the United Kingdom, which is an organization similar to AAAS, defines 3 aspects of scientific literacy that are consistent with AAAS‘s definition. These dimensions of scientific literacy include:  

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

Science content: understanding facts, laws, concepts and theories. Scientific inquiry: understanding of the scientific approach to inquiry. The ability to define scientific study and to discriminate between science and non-science. Social enterprise: understanding science as a social enterprise (Driver, 1996, pp.1213).

Although various individuals and organizations contribute slightly different definitions of scientific literacy, they tend to weigh science content and science processes equally. Take, for instance, Driver‘s position. She identifies scientific literacy as public understanding of science and states: Public understanding of science involves not only an understanding of empirical inquiry procedures, but also of the role of theoretical and conceptual ideas in framing any empirical inquiry and interpreting its outcomes (Driver, 1996, p.12). Aslan, Yalcin and Tasar (2009) define scientific literacy as ―individuals‘ ability to define, explain and predict the natural phenomena‖. Therefore; a scientifically literate person is able to evaluate the quality of scientific knowledge with its resources and production methods.

NATURE OF SCIENCE Being emphasized in Tasar (2007), developing an adequate understanding of nature of science is a desired outcome of science education at any level. Brief historical reviews on definition of the nature of science require multidimensional and inconsistent definitions developed in different disciplines (Bell, Lederman, and Abd-El-Khalick, 1998). Although people tend to use the nature of science and the nature of scientific knowledge interchangeably, they are not the same. Scientific knowledge refers to the products of science such as concepts, theories and laws. The nature of science, however, refers to both products and processes of science including the nature of scientific knowledge, the scientific enterprise, and scientists‘ work (Meichtry, 1993). In other words, the nature of science encompasses the nature of scientific knowledge and the nature of scientific processes which constitute how this knowledge is produced. Scientific processes are activities (e.g.

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observation and inference) which are related to the collection and interpretation of data and derivation of conclusions. The nature of science consists of the epistemological commitments underlying these activities (AAAS, 1990, 1993; NRC, 1996 as cited in Bell, Lederman, AbdEl-Khalick, 1998). There is no consensus on the definition of the nature of science among philosophers of science, historians of science, scientists and science educators. However, most philosophers, historians, scientists and science educators agreed on the following general characteristics of the nature of scientific knowledge as embedded within the nature of science. Scientific knowledge is: 

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Tentative: when new observations challenge prevailing theories, there will be a change in scientific knowledge. Regardless of how well a theory explains the observation, there might be another theory which may fit as well or better. Testing, improving, and discarding theories help scientists make increasingly accurate approximations to account for the world and how it works. It should be kept in mind that rejecting a theory and having a change in scientific knowledge is always slow. Instead, scientists modify the theories and keep most scientific knowledge stable. Empirically based: validity of scientific knowledge relies on evidence which would be obtained by observations and measurements taken in situations that range from natural settings to completely contrived ones. Theory laden: scientific knowledge is subjective because scientific observations are not theory neutral. What scientists will observe and how they will interpret these observations are influenced with scientists‘ theoretical commitments. When they encounter evidence that conflicts with their theories, scientists may not see the conflicts and they either ignore the evidence so that it fits their theories or modify their theories to account for the evidence (Brickhouse, 1990, p.60). Partly the product of human inference, imagination and creativity: scientists often use their imaginations and have tentative hypotheses about possible things that might happen. What data to pay attention to and how to interpret data depends upon these tentative hypotheses?

Socially and culturally embedded: Scientific knowledge is socially constructed by a community of scholars to serve the purposes of scientific community. Theories are generated in a social context and they are evaluated on the basis of generally agreed criteria. According to this view science is a culture with particularly powerful tools for understanding the natural world (Brickhouse, 1990). These general characteristics of the nature of scientific knowledge reflect the contemporary view of the nature of scientific knowledge and science. Based on these generally agreed characteristics, lets discuss scientists‘, philosophers‘ and science educators‘ perceptions of the nature of science.

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SCIENTISTS’ PERCEPTIONS If not only the nature of scientific knowledge but also the nature of science is considered, scientists recognize both processes and products of science. For example, Weisskopf (1989), a distinguished physicist who holds views consistent with the contemporary nature of science, defines science as a discipline which does not provide answers to definite questions. Science asks the why and how questions and therefore is the process of questioning not the acquisition of information (Weisskopf, 1989, p.30). Most scientists perceive the nature of scientific laws as if there is a high correlation between experience and generalization such that experience leads to generalization. They interpret science as ―the process and the product of a dynamic man-world interaction‖ (Durkee, & Cossman, 1976).

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PHILOSOPHERS’ PERCEPTIONS For Popper (1959), a positivist philosopher of science, a scientific system is the one that can be tested by experience. If a system can be tested and refuted, it is a scientific system (Popper, 1959). According to Popper, scientific knowledge needs to be based upon firm foundations and empirical evidence. A statement that is compatible with any possible evidence is not scientific. Insulation against refutation makes that statement not scientific but metaphysical. For Popper, scientific knowledge claims can never be proven or fully justified. They can only be refuted, and scientific knowledge grows by process of error elimination which requires us to be ready to change, to test, to refute, and to falsify these items if possible. There are no scientific generalizations beyond doubt, which means no human views are fully correct. Scientific generalizations are limited with the nature that human beings have access. Popperians perceive that human beings progress by criticism and refutation. Heavy reliance on empirical evidence and refutation process make Popper‘s views different than contemporary model of nature of science. Kuhn, a revolutionist philosopher of science, addressed the issue of relativity. He identified the importance of the framework and paradigm in the context of which a scientist‘s work takes place. Different paradigms lead scientists to live and work in different worlds. A knowledge claim put forward by a scientist from a framework might not be better or ―truer‖ then those put forward by a scientist from a different framework. An argument or a knowledge claim might be well warranted only relative to the framework or paradigm in which it was produced (Philips, 1989). Kuhn also distinguished between normal and revolutionary science. In normal science, scientists belong to a well understood paradigm in which they know what they are supposed to do and how to do it. Revolutionary scientists, in contrast to normal science, question the ground on which they stand- they question the science itself. According to Kuhn, all terms, even the most observational ones, are theoryladen and theoretical differences between different paradigms make us not able to compare the two theories with absolute precision by reference to data (Hull, 1996).

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SCIENCE EDUCATORS’ PERCEPTIONS For science educators, many scholarly analyses (Bentley& Garrison, 1991; Lederman, 1992 among others) cite the Lederman and Zeidler (1987) definition of the nature of science. That is, the ―nature of science most commonly refers to the values and assumptions inherent to the development of scientific knowledge‖ (Lederman & Zeidler, 1987, p.721). Lederman and Zeidler (1987) identified these values and assumptions with Rubba‘s (1977) six categories of characteristics of nature of scientific knowledge explained in his Nature of Scientific Knowledge Scale. According to these categories, scientific knowledge is amoral, creative, developmental, parsimonious, testable and unified. An individual‘s beliefs about how scientific knowledge fits into these categories reflect his/her understanding of nature of science (Lederman & Zeidler, 1987, p.721). Meichtry (1993), however, reports other science educators‘ definitions and components of nature of science as follows:  

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The processes of scientific inquiry and the developmental nature of knowledge acquisition in science depict the nature of science (Klopfer, 1969). [Science is] tentative, public, replicable, probabilistic, humanistic, historic, unique, holistic, and empirical (Schowalter, 1974). [Science is] tentative and revisionary (Cotham & Smith, 1981).

Later, Driver (1996) defines an understanding of the nature of science as ―…one‘s ideas about science, as distinct from ideas about the natural world itself (their scientific knowledge). At the heart of this is their understanding of the nature and status of scientific knowledge: how the body of public knowledge called science has been established and is added to; what our grounds are for considering it reliable knowledge; how the agreement which characterizes much of science (and essentially of all school science) is maintained‖ (p.13). Understanding the nature of science consists of an explicit understanding of how knowledge claims are produced, checked and validated. It also consists of understanding how scientific knowledge is socially and culturally embedded and how it is influenced with the social commitments and values on the choices and interpretations that scientists make (Driver, 1996).

SIGNIFICANCE OF THE ISSUE Based on the definitions given above, it can be posed that there is a strong connection between a person‘s understandings of the nature of science and scientific inquiry. This connection can be more visible in one‘s school science experiences. It has been argued that inquiry in school science can help individuals to promote an understanding of the nature of science. When an individual understands that scientific ideas and models change over time and that scientific ―theories‖ are never proven in an absolute or final sense, it may be easier for him/her to accept development of scientific understanding (Meichtry, 1993 as cited in Macaroglu, 1999).

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Although understanding the nature of science is accepted as the major component of scientific literacy, research studies suggest that teachers, both in-service and pre-service have limited understandings of the nature of science (Lederman and Zeidler, 1987; Duschl, 1990; Gallagher, 1991; Lederman, 1992; Meichtry, 1993; Tasar, 2009). For an effective science teaching there is a need for literacy in science. Literacy in science, which is scientific literacy, requires an understanding of the processes and nature of science accompanied with the ability to do scientific inquiry. Therefore science teachers should understand how scientists think and behave, and then they must develop methods to communicate this understanding to students. Being engaged in science teaching and learning requires individuals to be able to carry out research projects by asking questions, constructing hypotheses, predicting outcomes, designing experiments, analyzing data, and reaching conclusions. Science teachers also need to bring the attitude and world view of scientist into classroom. Therefore, they need to have a basic understanding of philosophies of science. Matson and Parsons, 1998 (as cited in Macaroglu, 1999) argued that a basic science content background, an ability to carry out the process of science, and a basic understanding of philosophies of science help teachers teach science as a conceptually oriented, minds-on/ hands-on problem solving, critical thinking activity which will promote science literacy among students. Teachers‘ understandings of nature of science are of particular importance because it influences decisions about what is taught and how it is taught (Brickhouse, 1990; Aldridge and Taylor, 1997). In other words; teachers‘ understandings of nature of science influence their classroom practice as well as influencing their ideas about how students learn.

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RESEARCH STUDIES ABOUT THE NATURE OF SCIENCE Tasar (2007) divided the major research areas in science education into six categories: the nature of content area and subject matter, the nature of science and scientific knowledge, the nature of teachers and learners, the nature of teacher training, the nature of teaching and learning, the nature of teaching and learning environments. Here in this chapter, we discuss what has been done in research studies about teachers‘ and students‘ understandings of the nature of science and scientific knowledge.

Students’ Understandings If scientific literacy refers to one‘s understanding of the concepts, principles, theories, and processes of science, a scientifically literate individual should develop a functional understanding of the nature of science. Therefore; an adequate conception of nature of science is an important attribute of the scientifically literate person. Researchers‘ have been interested in students‘ ideas about the nature of science for a number of years. Unfortunately, researchers focused on students‘ understandings of nature of science suggest that students do not have an adequate understanding (Lederman, 1992; Meichtry, 1993; Brickhouse, Dagher, Letts IV & Shipman, 1998; Tasar, 2009 among others). Here are most frequently used measurement scales developed to assess students‘ understandings of the nature of science and how these scales were used.

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The first formal instrument to assess students‘ conceptions about the nature of science, the Science Attitude Questionnaire, was administered by Wilson in 1954. Forty-three high school students participated into study. Wilson found that students possessed negative attitudes towards science and believed that the primary objective of science was to uncover natural laws and truths (Lederman, 1992). Mead and Matraux (1957) designed the first qualitative approach to assessing students‘ conceptions about the nature of science. Their nationwide study included 35,000 randomly chosen participants who responded to the question ―what do you think about science and scientist?‖ Their data analysis indicated that students possessed negative attitudes towards science. Students also perceived the primary objective of science as to achieve the ―truth‖ of the natural world. This finding was consistent with Wilson‘s research findings (Lederman, 1992). These two early studies employed very different research approaches and revealed students‘ extremely limited understandings about the nature of science. That is, high school students believed that scientific knowledge was absolute. Consistently, they held absolutist view of the nature of scientific hypotheses and theories (Wilson, 1954; Klopfer & Cooley, 1961; Korth, 1969; Broadhurst, 1970; Aikenhead, 1972, 1973; Rubba, 1977; Body, 1979 as cited in Lederman, 1992). Among the instruments designed with the purpose of assessing students‘ conceptions of the nature of science, the Nature of Scientific Knowledge Scale (NSKS), designed by Rubba in 1977, has been the most frequently used and cited one in the literature. Lederman (1986) and Meichtry (1992) were among the science educators who used the NSKS in their research regarding students‘ understandings of the nature of science (as cited in Meichtry, 1993). Although there is sufficient evidence that students do not have an adequate conceptions of nature of science, Lederman came up with a contradictory result. Lederman used NSKS to assess what students understand about the nature of science and to compare their understandings with the Notion of an adequate conception. That is, acknowledging the values and assumptions that are inherent to the development of scientific knowledge and weighing the products and processes of science equally. In this study, ―adequate conception of nature of science‖ is identified in details in the contemporary model of the nature of science (see appendix A). Lederman found that students believed scientific knowledge to be amoral, a product of human creativity, tentative, subject to empirical test, and unified. This result led Lederman to question the current perception that students and often times their teachers possess inadequate conceptions of nature of science. Lederman (1986) explained this situation by introducing two issues. First one is the lack of precise criteria for what constitutes an adequate conception of the nature of science. As stated earlier, there was no specific definition of the nature of science which would serve as a criterion to assess whether their conceptions were adequate or not. Second one is the characteristics of the research population. The population used in Lederman‘s research was representative of a scienceoriented population and being science-oriented influence students‘ understandings of the nature of science positively (Meichtry, 1993). Meichtry (1992) modified Rubba‘s NSKS by excluding the items address parsimonious and a moral aspect of the nature of science. Meichtry‘s research was conducted to determine the effect of a traditional middle school science program on students‘ understandings of the nature of science. Thirteen hundred 6th, 7th and 8th grade students participated and research result revealed that students‘ understandings of the nature of science were less than adequate. Data indicated that students did not believe scientific knowledge to be (1) partially a product

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of human creativity, (2) tentative in nature, (3) and based on empirical evidence (Meichtry, 1993, p.435). In the late 1980‘s and 1990‘s, ethnographic research methods in which data were collected through observations, interviews, and other artifacts either compensated or replaced the quantitative data collection instruments (Brickhouse et al., 1998). Driver et al. (1996) focused on three issues: the purpose of scientific work, the nature and status of scientific knowledge, and science as a social enterprise. They conducted a study with 9, 12, and 16 year old students and found that students‘ understandings of theory fell under one of the three following categories:  

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Theory is taken for granted statement of how the world is, and there is no distinction between theory and evidence. Theory and evidence are distinguished, but theory is perceived as an attempt to correlate variables without underlying mechanisms. Theories are perceived as involving the positing of a theoretical model whose properties are then related to observed changes in the system to be explained (Brickhouse et al., 1998, p.2).

In the same study, Driver (1996) reports from Shapiro (1989, 1994) that research findings support evidence for a close relationship between students‘ progress in conceptual understanding in science and their view of science and how to best learn it. Those who perceived scientific knowledge as revisable rather than static were less likely to believe that science learning depends on memorization. They achieved a more integrated understanding of the topic. Driver makes three assertions based on the findings of this research study. When students are taught the nature of science, first, they understand the relationship between evidence and explanation that is critical to science learning. Students‘ interpretations of evidence are influenced by their commitment to a theory. Second, they understand the similarities between their own learning and the historical progress in scientific understanding. Third they develop a stronger sense of ownership of the scientific enterprise and to greater public support for science and technology (Driver, 1996). Lederman and Lederman (2009) state a clear movement from traditional convergent assessments to more open-ended ones in the history of Nature of Science assessment. Most of the researchers realized the difficulty of assessing a complex construct, like nature of science, with multiple choice and likert scale items. Lederman‘s also indicate that interviews and open-ended assessments are time consuming to conduct and score. Although teachers and science educators are interested in young students‘ understandings of the nature of science and scientific inquiry, there is a lack of instrument to assess their understandings. Lederman and Lederman (2009) report their efforts to revise some instruments, like VNOS-E (Lederman & Ko, 2003) and VOSI-E (Lederman & Ko, 2004), into an oral protocol and scoring approach that could be used to provide data from young students. Face, content and construct validity of this instrument, oral protocol, are provided in Lederman and Lederman (2009). The instrument reported above cannot be used as a large scale instrument. Therefore, science educators aim to develop a valid large scale instrument. Zilker, Holliday, Fischer, Kauertz, Lederman and Lederman (2009) concerned with the question if historical case

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studies can be enlisted to build up appropriate context for a test to assess competencies in the field of nature of science and scientific inquiry. They proposed a large scale instrument by using historical contexts to assess students‘ competencies in the areas mentioned above. Zilker et al (2009) report two studies. Neither studies (First study with 288 students from Germany and the United States, second study with 1080 students from Germany) showed significant effect of the context on difficulty. Thus, they concluded those historical contexts are appropriate for that test development (Zilker et al, 2009). Another research study on competencies in understanding the nature of science and scientific inquiry reveal that students in higher grades receive higher scores in the inquiry competence test and a nature of science questionnaire. This result suggest that students display better inquiry and nature of science competencies when they have more learning experiences in schools (Kremer, Grube, Urhahne, Mayer, 2009). One way of improving students‘ conceptions of the nature of science is to teach it explicitly. Explicit teaching of the nature of science will serve as a means to accomplish scientific literacy. Therefore, it is necessary to explore what teachers know about the nature of science. Do teachers have adequate understanding of the nature of science so that they can teach? What research studies tell about teachers‘ (both prospective and in-service) understandings of the nature of science will be presented in the following section.

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Teachers’ Understandings Similar to reports of students' conceptions, researchers suggest that teachers do not possess adequate conceptions of the nature of science (Miller, 1963, Schmidt, 1967, Carey & Strauss, 1968, 1970 as cited in Lederman, 1992). Initial research in this area was conducted by Miller (1963) and Schmidt (1967) who compared secondary science teachers‘ understandings of nature of science with students‘ understandings by comparing their Test on Understanding Science (TOUS), an instrument developed by Klopfer and Cooley in 1961, scores. Seven hundred thirty-five secondary science students and 51 secondary biology teachers participated in Miller‘s study. Surprisingly, students scored higher on the TOUS than 25% of the science teachers. Miller concluded that high school science teachers did not understand science any better than their students. Schmidt (1967) replicated Miller‘s study with a smaller sample and reached similar findings. Neither students nor teachers had adequate understanding of the nature of science (Lederman, 1992). Following Miller and Schmidt, in 1970, Carey and Strauss assessed in-service secondary science teachers‘ understandings of nature of science with a different scale, the Wisconsin Inventory of Science Processes (WISP). Similarly, they found that regardless of their academic success in college and their years of experience in teaching, experienced teachers did not have an adequate understanding of nature of science (Lederman, 1992). Researches that focused on assessing science teachers‘ understanding of the nature of science were guided by the two assumptions reported in Bell et al (1998).  

Teachers translate their conceptions directly to their classroom practice, Teachers‘ and students‘ conceptions are significantly related to each other.

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Do teachers' conceptions of the nature of science really influence their classroom practice? This question was examined by number of researchers and their research results differed to some extent. Some research findings reveal that there is no significant relationship between teachers‘ understanding of the nature of science and their classroom practice (Lederman & Zeidler, 1987, Duschl & Wright, 1989). Lederman and Zeidler (1987) administered NSKS to 18 senior high school biology teachers. In order to assess the relationship between their conceptualization and classroom practice, they conducted 3 intensive, qualitative classroom observations for each participant. According to pre and post NSKS test results participants were categorized as ―high‖ and ―low‖ teachers. In contrast to literature, data revealed that ―simply possessing valid conceptions of the nature of science do not necessarily result in the performance of those teaching behaviors which are related to improved student conceptions‖ (Lederman, & Zeidler, 1987, p. 731). There are also other research data that support a direct influence of teachers' conceptions of the nature of science on classroom practice (Brickhouse, 1989, 1990; Gallagher, 1991, Lakin & Wellington, 1994). Findings of Brickhouse (1990) and Lakin & Wellington (1994), as cited in Aldridge and Taylor (1997), reveal that teachers‘ beliefs about the nature of science affect the way in which they teach science. Although there are contradictory research results, there is an agreement among researchers that curriculum constraints, administrative policies, and teaching context might have a strong influence on the translation of teachers' conceptions into classroom practice (Lederman, 1992). Translation of teachers‘ conceptions into classroom practice is also influenced by teachers‘ intentions, content knowledge, pedagogical knowledge, students‘ needs, teacher autonomy, time (Gess-Newsome, & Lederman, 1995), pressure to cover content (Duschl, & Wright, 1989; Hodson, 1993 as cited in Bell et al., 1998), teachers‘ concerns with classroom management and organization (Smith & Neale, 1989; Hudson, 1993; Lantz, & Kass, 1987; Lederman, 1995 as cited in Bell et al., 1998), institutional constraints, and teaching experiences (Brickhouse & Bodner, 1992; Lederman, 1995 as cited in Bell et al., 1998). Brickhouse (1990) studied the possible link between teachers‘ views of the nature of scientific knowledge and the methods they used to help students construct knowledge of science. In her study she worked with three secondary in-service science teachers. One beginning teacher, heavily relied on the textbook and did not question it, one held a view consistent with philosophers of science like Kuhn, and one held a view consistent with Popper. Brickhouse (1990) compared the teachers‘ views of the nature of scientific theories, the nature of scientific processes, and the progression and change of scientific knowledge. One of her more interesting findings was the divergent views of the two experienced teachers regarding the nature of scientific theories and the relationship between their views and classroom practices. One of these experienced teachers, Lawson, who held a Kuhnian view of science, perceived theories as tools to solve problems. The other experienced teacher, Cathcart, who held a more positivist view of science, perceived theories as truths that had been uncovered through rigorous experimentation. The divergence in their perceptions of the nature of scientific theories and scientific processes influenced their classroom practices. Consistent with their perceptions of the nature of scientific theories, they had different instructional goals for their students. Lawson‘s instructional goal for her students was to have them use theories in problem solving whereas Cathcart wanted his students to know what the scientific theories were. For Lawson, knowing a theory was not enough, she wanted to see her students apply theories in problem solving.

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Similarly, consistent with their perceptions of the nature of scientific processes, the teachers were different in how they taught. Cathcart‘s science activities required students to follow directions to get correct answers. On the other hand, for Lawson, prediction of classroom demonstrations or laboratory activities was a central aspect of her teaching. She was not looking for the ―right answer‖. Brickhouse found that the teachers‘ views of how scientists construct knowledge were consistent with their beliefs about how students should learn science, as well as how they taught science. The teachers‘ understandings of what science was and how students learned science in schools have formed a consistent system of beliefs for guiding classroom activities (Brickhouse, 1990, p.60). Therefore, teachers‘ understanding of the nature of science is of particular importance because it can influence decisions about what is taught and how it is taught. Aldridge et al. (1997) report similar research findings that support Brickhouse‘s work. One of the cross national research studies on teachers‘ understanding of the nature of science and school science was designed by Aldridge and colleagues (1997). They developed a questionnaire, Beliefs about Science and School Science Questionnaire, BASSSQ, to identify teachers‘ beliefs about the nature of science and provide insight into ways in which those beliefs influence their teaching practices (Aldridge, Taylor, & Chen, 1997). The purpose of Aldridge et al. in using BASSSQ was not only to construct the validity and reliability of the questionnaire items but also to raise some issues concerning the influence of teachers‘ beliefs about the nature of science on their teaching practices. They also used the instrument to understand the teachers‘ ability to differentiate scientists‘ science from school science. The instrument helped researchers to gather both qualitative and quantitative data to determine the teachers‘ perceptions of science ranging on a continuum from objectivist (which is grounded in the empiricist tradition) to postmodern (which is grounded in the new physics and contemporary philosophies of science). Although the results revealed that there were some problems with the internal consistency and reliability of the sub-scales of the instrument, the research raised two important issues related to the use of BASSSQ. First, teachers‘ responses to BASSSQ depend on their readings of the instrument. If teachers read BASSSQ from a philosophical perspective they can make the differentiation between science and school science. Second, teachers‘ curriculum contexts influence their responses to items. The same teacher may give different responses to the same item due to whether he/she is thinking about junior or senior school science (Aldridge et al., 1997). These limitations of the instrument suggest that these kind of quantitative data collection instruments need to be accompanied with qualitative research methods to explore teachers‘ rationale behind their responses. It is worth mentioning that Taylor has other studies and cross national research on developing the instrument to be used in identifying teachers‘ and/or students‘ understandings of the nature of science that are not the focus of this paper. Research studies about teachers' conceptions of the nature of science have led researchers to focus on pre-service science teachers. Mellado (1997) reports from Hewson &Hewson (1989) that from a constructivist perspective, in-service and pre-service science teachers‘ conceptions of science and how to teach and learn it are based on their own years in school. Mellado (1997) also reports from other studies (Furio, Gill, Pessoa De Carvalho and Salcedo, 1992; Gill, 1991, 1993) that inadequacies in science teachers‘ classroom thinking must be questioned in teacher education programs. It is easier to assist pre-service teachers because we still have contact and we have more access to influence their understanding of nature of

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science. The only point that is difficult to assess is to make the connection between their understanding of nature of science and classroom practice (Bell et al., 1998). The importance of pre-service elementary teachers‘ understanding of the nature of science was examined (Harty, Samuel, & Anderson, 1991 among others). In their research, Harty, Samuel, and Anderson (1991) examined differences among three elementary school science pre-service teacher preparation course sequences with respect to understandings of the nature of science, attitudes toward science and attitudes towards science teaching. Three groups of pre-service teachers included 24, 25, and 22 potential teachers participated in study. They administered the Nature of Science Scale, NOSS, (Kimball, 1967) to assess pre-service teachers‘ understanding of the nature of science, Shrigley Science Attitude Scale, SSAS, (Shrigley, 1974) to examine pre-service teachers‘ attitudes toward science, and Pre-service Elementary Teacher Attitudes Toward Science Teaching Scale, which they developed specifically for the study, to examine pre-service teachers‘ attitudes toward science teaching. Their research findings revealed that developing an understanding of the nature of science is independent from developing better attitudes towards science and science teaching, however, better understanding of the nature of science might influence positive attitudes towards science and science teaching. Positive attitudes towards science and science teaching might help individuals in terms of achieving the desired level of scientific literacy by encouraging them to learn science. Consistent with the positive relationship between better understandings of nature of science and having positive attitudes toward science and science teaching, Aldridge and Taylor (1997) suggest that the ways in which people interpret events are influenced by their constructs, schema, beliefs, and understandings. That is, both for teachers and students understanding the nature of science is influential in how they make their interpretations. However, research studies have shown that neither students‘ nor teachers‘ understandings are consistent with contemporary conceptions of the nature of science (Lederman, 1992). The factors that influence pre-service secondary science teachers' conceptions of the nature of science have been examined for a number of years. Pre-service secondary science teachers‘ conceptions of nature of science were first investigated by Carey and Strauss (1968) as cited in Lederman (1992). They used WISP to assess 17 pre-service secondary science teachers‘ understandings of nature of science. Additionally, they investigated the effectiveness of a science methods course to improve participants‘ conceptions of nature of science. Research suggested that similar to in-service ones, pre-service science teachers did not have an adequate understanding but their viewpoints could significantly be improved by a methods course specifically oriented toward the nature of science (Lederman, 1992). Other research studies regarding pre-service secondary science teachers‘ conceptions of the nature of science reveal that their lack of background in history and philosophy of science clearly influences their science teaching (King, 1991 as cited in Lederman, 1992). Understanding of the nature of science does not depend on being exposed to accurate readings or instruction; it depends on pre-service teachers‘ beliefs about science (Lederman, 1992). Lederman and Zeidler (1987), and Gallagher (1991) support the above studies by suggesting prospective teachers‘ have more exposure to the nature of science and experience teaching it. There are only few studies deal with pre-service elementary teachers‘ views about scientific knowledge and the nature of science. Kaulaidis and Ogborn (1989) administered 16-item multiple choice questionnaire to beginning and pre-service science teachers with the purpose of describing and comparing their views about scientific knowledge. Questionnaire

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consisted of 4 groups of items: scientific method, demarcation of science from non-science, change in scientific knowledge, and the status of scientific knowledge. According to how they responded subjects were categorized into 4 categories of philosophical belief: inductive, deductive, rationalist, and relativist. Researchers concluded that neither beginning nor preservice teachers possessed views which would consistently be associated with a particular philosophical view (Kaulaidis, & Ogborn, 1989). Moreover, they might hold dualistic views for components of the nature of science. Bloom (1989) also assessed pre-service elementary teachers‘ understanding of the nature of science by administering a questionnaire consisted of 6 questions related to knowledge of science, theories, and evolution. Eighty pre-service elementary teachers enrolled in methods courses participated in the study. His qualitative data analysis revealed that pre-service teachers were confused about the meaning and the role of scientific theory, (e.g., theories were related to belief in one‘s own thought apart from empirical observation). Bloom‘s most significant finding was the influence of teachers‘ beliefs on their conceptualization of science. For example, a teacher‘s belief significantly influences his/her conceptualization of science, the theory of evolution and how evolution would be taught (Lederman 1992, p.344). In another study, Abd-El-Khalick, Bell, and Lederman (1998) aimed to delineate the factors that mediate the translation of pre-service teachers‘ conceptions of the nature of science into instructional planning and classroom practice. Fourteen pre-service secondary science teachers participated in the study. Prior to student teaching, participants responded to an open ended questionnaire designed to Abd-El-Khalick et al (1998) reported that the following 3 assertions reflected pre-service teachers‘ understandings of the nature of science after participating in a Master of Arts in Teaching (MAT) program:

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

 

Science is empirically based (Bell et al., 1998; Kim, German, & Patton, 1998) and this empirical nature sets science apart from other disciplines. The empirical nature of science is directly related to tentative nature of science. Because of this empirical nature we have an opportunity to find new evidence. Then, the accumulation of new evidence results in changes in theories. Therefore, the perceived role of observation and theory helped pre-service teachers to understand the tentative nature of science. Consistent with its tentative nature, science is subjective. Development of scientific ideas depends on scientists‘ individuality, beliefs, and backgrounds. There is a distinction between law and theory. The law is a statement or description of discernible patterns in an observable phenomenon whereas the theory is an inferred explanation for this phenomenon (Bell et al., 1998).

Bell et al (1998) also studied how pre-service teachers perceived learning and teaching the nature of science. According to Bell et al. pre-service elementary teachers perceived that doing science or being engaged in science related activities would end up with implicit learning of the nature of science. They confused the nature of science with the processes of science and would prefer manipulative/hands-on activities. They had a tendency to combine a process or inquiry oriented teaching approach with an attempt to teach the nature of science implicitly (Bell et al., 1998). Even if prospective elementary teachers develop a more contemporary view of the nature of science, the constraints present for in-service teachers would make it difficult for pre-

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service teachers to translate these views into their teaching. Bell et al (1998) reported that perceiving the nature of science less significant than science content and science processes, concern for students‘ needs and attitudes, and pre-occupation with classroom management and routine chorus were among the factors that constrained pre-service elementary teachers in translating their perceptions of the nature of science into classroom practice. Additionally, Bell et al (1998) found that similar to the case of secondary science teachers, pre-service teachers‘ discomfort with understanding of nature of science, their focus on themselves rather than on what they taught in class, and constraints created by cooperative teachers have also influenced this translation. Limited number of studies report on attempts to assist prospective elementary teachers develop scientific views consistent with contemporary ones held by science researchers and science educators. For example, in their two-year elementary science teacher preparation program, Starr, Zembal-Saul, and Kracjik (1997) used an inquiry orientation toward science teaching as a program framework. In an inquiry orientation program, teachers let students define and investigate problems, draw conclusions, and assess the validity of knowledge from their conclusions. Research findings suggest that students developed a better understanding of the importance of cognitive engagement through the use of prediction, discussion, inquiry activities, and questioning (Starr et al., 1997). It might be concluded that inquiry oriented programs help students develop better conceptions of the nature of science. Similar to Starr et al. (1997), Aydeniz, Hagevik & Roberson (2009) report on the lack of attempts to assist students to develop scientific views consistent with contemporary ones. They argue that school science curricula and science instruction in the classroom including college classrooms promote objectivist views of science and focus on conceptual and procedural aspects of science with limited attention to the epistemic aspect of science. Aydeniz et al. (2009) focused on prospective elementary teachers‘ understanding of the nature of science through engagement in conducting inquiry-based experiments and the use of inscriptions in their study. The purpose of their study was to determine if the use of inscriptions in science notebooks along with explicit teaching and reflection on the nature of science could enhance prospective teachers‘ views of science. They used situated learning theory to understand the developmental trajectory of prospective elementary school teachers understanding about science through inscriptions. Multiple data sources were students‘ responses to VNOSD-2, a structured interview protocol and science notebooks used for designing inquiry experiments, recording their results, construction of inscriptions and analysis of data. Research results show that the situated learning model enhanced participants‘ understanding of science over the course of a semester. Considerable evidence shows that a teacher‘s conception of the nature of science influences how he/she teaches as well as what is taught (Brickhouse, 1990; Aydeniz et al., 2009). It has also been shown that designing methods courses centered around an explicit emphasis on the nature of science and scientific inquiry helps pre-service teachers develop adequate understandings of the nature of science (Starr et al., 1997 among others). For these reasons it is important that teachers‘ understanding of the nature of science and how it can be improved need to be the focus of future research.

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IF BELIEFS ABOUT THE NATURE OF SCIENCE ARE PUT INTO PRACTICE The research, presented in this section, focuses on prospective elementary teachers‘ understandings of the nature of science and its reflections in practice. This research study is designed in a mixed-qualitative and quantitative- manner. 49 prospective elementary science teachers, who attend to science education methods course in a big teacher training institution in Istanbul, participated in this research. Throughout the course, researchers focused only on participants‘ current epistemological beliefs other than focusing on the change in their beliefs during the instruction. The research study took place in 2004-2005 academic years.

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Data Collection Scientific Epistemological Beliefs Scale: 30-item, likert type scale translated and adapted in Turkish from Pomeroy‘s (1993) work by Deryakulu and Bikmaz in 2003 (Oztuna, 2006). Validity and reliability study of the scale was also done by the same researchers. The scale basically displays both traditional and contemporary beliefs about science. There were 22 items to reflect traditional beliefs about science, coded (+), and 8 items to reflect contemporary beliefs about science, coded (-). High scores from the scale represent more traditional views about science and in contrast, low scores from the scale represent more contemporary views about science. Items like ―Science aims to reach knowledge which constitutes objective explanations‖ represent traditional view whereas, ―Intuition plays an important role in scientific discoveries‖ represent contemporary views about science. Scale also consists of some items addressing science process skills which prospective teachers need to know and apply. ―What is knowledge?‖- Open-ended questionnaire: questionnaire contains 8 open-ended questions and 24 choice items developed by the researchers. ―What is knowledge? What is the source of knowledge? Define the valid knowledge. How people reach the knowledge?‖ are among these open-ended questions. An example to choice items is as follows: Knowledge is:    

Based on rationale Formed at the end of trial and error process Objective Formed from observations

Data Analysis and Evaluation Data corresponding scientific epistemological beliefs scale were analyzed in a statistical program, SPSS. Open-ended questions and written documents were analyzed by using opencoding technique.

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Findings Findings from Scientific Epistemological Beliefs Scale: Table 1 displays participants‘ total scores from the scale. Table 1. Participants total scores from Scientific Epistemological Beliefs Scale Score interval 70- 80 81-90 91-100 101-110 111-120 Total

Frequency 1 0 13 27 8 49

Percentage (%) 2.0 0 26.6 55.1 16.3 100

As seen in table 1; 98% of the participants got high scores (between 91 and 120) from the scale. Although the highest score from the scale could be 150, it is found for the participants as 117. The lowest score for them was 71. 55% of the participants got scores between 101and 110. As high scores from the scale represents traditional views about science, it can be emphasized that prospective elementary science teachers participated in this research study have traditional views of science. Findings from open-ended questionnaire: Data gathered from open-ended questions were coded in two groups: ―definition of knowledge‖ and ―sources of knowledge‖. Table 2 and table 3 display related codes consecutively. Related tables also display the frequency and percentage of codes. Frequency of codes might be more than number of participants. The reason of this difference in numbers is the multiple codes that learners‘ views would have.

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Table 2. Codes for definitions of knowledge Codes

Frequency of repetition Experience 15 Observation and Exp. 11 Scientific research 8 Intellect-rationale 7 Objective reality 4 Profit approach 3 Truth 2 Others 5 Not know or not answered 5

Percentage of total frequency (%) 30.61 22.45 16.33 14.29 8.16 6.12 4.08 10.20 10.20

Percentage of frequency of repetition (%) 25.00 18.33 13.33 11.66 6.66 5.00 3.33 8.33 8.33

Table 2 shows that codes from most participants (43.3%) display an empiricist approach to knowledge. Almost none of the participants, except the ones shown in the row of others (2 students), mentioned a contemporary view about science. Data show that participants‘ definitions of knowledge and valid knowledge refer only scientific knowledge. In other words, data emphasize that prospective elementary science teachers only think about scientific knowledge when they are asked about valid and reliable knowledge.

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Esra Macaroglu Akgul Table 3. Codes for sources of knowledge

Codes

Frequency of repetition Science/scientific research 10 Observation and experiment 9 Experience 8 Nature 8 Intellect-rationale 8 *religion 6 *intuition and imagination 6 Authority 5 Environment and everyday life 5 *society and culture 3 Curiosity 2 Other 6

Percentage of total Percentage of frequency frequency (%) of repetition (%) 20.41 13.16 18.37 11.84 16.33 10.53 16.33 10.53 16.33 10.53 12.25 7.89 12.25 7.89 10.20 6.58 10.20 6.58 6.12 3.95 4.08 2.63 12.25 7.89

Table 3 shows parallel results with table 2. Participants mostly perceive the experiment and rationale as the sources of knowledge. Student generated artifacts were used secondary sources of data to understand participants‘ epistemological beliefs in details. Data from these artifacts are consistent with data presented in the tables above. Participants were asked to define learning by writing an analogy about it. Table 4 displays these definitions and analogies.

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Table 4. Definitions and analogies of learning Teacher Artist Flower Baker Miner Engineer Root Coach Hearth Fisherman Archeologist

Student Painting (2 times) Bee Dough Gold worker sapling Succor Body Someone trying to cross the sea Work of history

Definitions and analogies presented in table 4 represent ―behaviorist approach to learning‖ in participants‘ views. Only in the last two of the analogies guidance is emphasized as the role of a teacher. Data displays that prospective elementary science teachers participated in this research study have traditional views in term of their epistemological beliefs. Research results are consistent with the research studies in other countries done by Odgers (2003), Tsai (2002), and Eick (2000). What most prospective science teachers understand from knowledge is scientific knowledge which can be proven and objective. Oztuna (2006) argues that individuals, who count experiment as the basis of knowledge, believe the emptiness of human

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mind at birth. Those who count mind as the basis of knowledge believe uncertainty of senses in our experiences. Experiences and senses are subjective and change from person to person. Therefore, it makes hard to have something common. On the other hand; some believe both, experience and mind, as the basis of knowledge. They argue the necessity of both in forming a valid knowledge. In this research study it is seen that there is a consistency between prospective science teachers‘ epistemological beliefs and understandings about teaching and learning. They hold traditional views in both. In their research studies; Clark and Peterson (1986) and Doyle (1990) emphasized influence of teachers‘ beliefs on their thinking and influence of their thinking on their practice in teaching. Lederman (1992) and Appleton and Asoko (1996) add some other research studies consistent with this argument, addressing the interaction between the beliefs about the nature of science and understandings about teaching and learning. The research study presented in this chapter has also consistent results with the studies mentioned above. In order to understand what happens if beliefs are put into practice in details, 5 of the participants who enrolled in a course on practice teaching were studied qualitatively. Data sources were interviews, researcher‘s observations in their classroom (during practice teaching) and portfolios which include self reflection papers of the participants. Qualitative data, obtained from the sources described above led researchers focus on how prospective science teachers put their epistemological beliefs into practice. Qualitative data analysis ended up with cases. Based on the observations and portfolio analysis, 4 of the cases were traditional and one was constructivist in terms of their epistemological beliefs. Participants‘ definitions of scientific knowledge, science, teaching and learning change according to epistemological beliefs they hold. Traditional ones define scientific knowledge by making emphasis on its production as; ―…it [scientific knowledge] is produced by an authority at the end of observations and investigations…‖. They also put emphasis on characteristics of scientific knowledge as; ―…trustable, gives truth, solves problems, objective and investigable‖. These participants‘ definitions of science were consistent with the definitions above, and include the processes of science to some extent. They listed the dimensions of science as ―…observation, experiment, universality, investigating the truth, systematic work…‖. The constructivist participant‘s definitions of science, scientific knowledge, teaching and learning were different than traditional ones mentioned above. She perceived scientific knowledge as ―making meanings from facts‖ and emphasized the components of scientific knowledge as ―trustable, but not absolute and objective. Different from other participants she mentioned the process side of science in more details. Her ideas clearly state that steps in scientific processes can change. Cultural and social values as well as personal and emotional values of scientist can interfere the scientific process. Five participants‘ views on learning and teaching science also differ according to their epistemological beliefs. Traditional participants‘ definitions of learning are; ―…[learning] is taking knowledge into long term memory by repetition,…(learning) causes change in behaviors‖. Alternatively, constructivist one defines learning as; ―…[learning] is a process which develops according to personal interests and developmental needs of individual‖.

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Similar to their definitions of learning, there are differences on participants‘ definitions of teaching. Following excerpts from interviews display how their definitions of students‘ roles differ. ― student is knowledge receiver…‖ (traditional) ― student is the one who thinks analytically, who is aware of his interests and needs and understands personal differences…‖ (const.) The excerpts above display different roles they defined for students. Based on these roles and other definitions mentioned above, following definitions of teaching, science, and scientific knowledge may be interpreted accordingly. Teaching is knowledge transfer from teachers to students. The knowledge is the scientific one if it is produced by an authority with research studies and investigations. It gives the truth. Science is the process to help us finding the truth.(traditional) Teaching is facilitating the environment for conceptual meaning making. Learning is an individual process of meaning making. Science is not the only way but a way of knowing. (Constructivist). In-class observations of prospective teachers participated in this research study support evidence for how their classroom practice change across their epistemological beliefs cited above. First variation among the participants observed practice is their methods of instruction. Traditional ones used lecturing most of the time, whereas constructivist one facilitated a learning environment in which students would be active. Although traditional participants used some teaching techniques like concept mapping, V diagrams, experiments and analogies in their practice teaching, they preferred their students to be passive. They mostly used multiple choice items or short answered questions for assessment and evaluation. Participant, holding constructivist views with respect to epistemological beliefs, used similar techniques but in a different context. She used techniques mentioned above and materials in a way that would enable her students to be active. She worked as a guide and made her students participate in their own learning. Her in-class activities led students ask questions about the issue taught, brainstorming and make inquiries, and experience different solutions to their problems and making their own meaning for these experiences. She did performance-based assessment in her class by using student generated artifacts and self reflection reports. As reported in the last two paragraphs; prospective elementary science teachers‘ epistemological beliefs affect their classroom practice. Therefore; individuals‘, especially teachers‘ and prospective ones‘ beliefs need to be investigated in details.

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Eick, C. (2000). Inquiry, nature of science, and evolution: The need for a more complex pedagogical content knowledge in science teaching. The Electronic Journal of Science Education (online) 4, (3). http://unr.edu/homepage/crowther/ejse/eick.html. Date: 22.09.2005/14:43. Gallagher, J. J. (1991). Prospective and practicing secondary school science teachers‘ knowledge and beliefs about the philosophy of science. Science Education, 75(1), 121134. Gess-Newsome, J., & Lederman, N. G. (1995). Biology teachers‘ perceptions of subject matter structure and its relationship to classroom practice. Journal of Research in Science Teaching, 32, 301-325. Harty, H., Samuel, J. V., & Andersen, H. O. (1991). Understanding the nature of science and attitudes toward science and science teaching of pre-service elementary teachers in three preparation sequences. Journal of Elementary Science Education, 3(1), 13-22. Hull, D. L. (1996). A revolutionary philosopher of science. Nature, 382, 203-204. Isenberg, J. P. (1990). Teachers‘ thinking and beliefs and classroom practice. Childhood Education. (66)5, 322-327. Kim, Y., German, P. J., & Patton, M. (1998, April). Study of concept maps regarding the nature of science by pre-service secondary science teachers. Paper presented at the annual convention of the National Science Teachers Association, Las Vegas, NV. Koch, A., & Eckstein, S. G. (1995). Skills needed for reading comprehension of physics texts and their relation to problem solving ability. Journal of Research in Science Teaching, 32, 613-628. Koulaidis, V., Ogborn, J. (1989). Philosophy of science: an empirical study of teachers‘ views. International Journal of Science Education, 11(2), 173-184. Kremer, K., Grube, C., Urhahne, D., Mayer, J. (August, 2009). Exploring competencies in understanding the nature of science and scientific inquiry. Contemporary science education research: international perspectives. Paper presented at ESERA. Lederman, N. G., & Zeidler, D. L. (1987). Science teachers‘ conceptions of the nature of science: do they really influence teaching behavior? Science Education, 71(5), 721-734. Lederman, N. G. (1992). Students and teachers conceptions of the nature of science. Journal of Research in Science Teaching, 29(4), 351-359. Lederman, N.G., Lederman, J.S. (August, 2009). Development of a valid and reliable protocol for the assessment of early childhood students‘ conceptions of nature of science and scientific inquiry. Contemporary science education research: international perspectives. Paper presented at ESERA. Macaroglu, E. (1999). Prospective elementary science teachers’ understanding about scientific inquiry and its role in school science. Unpublished Doctoral dissertation. Pennsylvania State University, PA. Mayer, V. J. (1997). Global science literacy: An earth system view. Journal of Research in Science Teaching, 34, 101-105. Meichtry, Y. J. (1992). Influencing student understanding of the nature of science: Data from a case of curriculum development. Journal of Research in Science Teaching, 29(4), 389407. Meichtry, Y. J. (1993). The impact of science curricula on students views about the nature of science. Journal of Research in Science Teaching, 30(5), 429-443.

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Mellado, V. (1997). Pre-service teachers’ classroom practice and their conceptions of the nature of science. Manuscript submitted for publication. National Research Council. (1996). National science education standards. Washington, DC: National Academy Press. Odgers, B. (2003). Teachers‘ beliefs about the nature of science and science education in relation to recently introduced constructivist syllabuses in secondary schools in quensland, Australia. Hawaii International Conference on Education Proceedings http://www.hiceducation.org/Edu_Proceedings/Barbara%20M.%20Odgers.pdf Oztuna, A., Akgul, E. (2006). Prospective elementary science teachers‘ epistemological beliefs. Procedia Social and Behavioral Sciences 1 (2009) 2529–2533. Pajares, M. F. (1992). Teachers‘ beliefs and educational research: cleaning up a messy construct. Review of Educational Research. (62)3, 307-332. Philips, D. C. (1989). Philosophy, science, and social inquiry. Elmsford, NY: Pergaman Press. Popper, K. (1959). The logic of scientific discovery. New York: Routledge. Starr, M., Kracjik, J., & Zembal-Saul, C. (1997, April). Preparing elementary science teachers: An application of research and practice. Paper presented at the annual meeting of the National Association for Research in Science Teaching, Chicago, IL. Sutman, F.X. (1996). Scientific literacy: A functional definition. Journal of Research in Science Teaching, 33, 459-461. Tasar, M.F. (2007). Reflection and remarks on the conversation ―the past, present and the future of the nature of science research‖ with Norman Lederman. Eurasia Journal of Mathematics, Science and Technology Education. (3)4, 383-386. Tsai, C. C. (2002). Nested epistemologies: science teachers‘ beliefs of teaching, learning and science. International Journal of Science Education. (24)8, 771-783. Weisskopf, V. F. (1989). The privilege of being a physicist. New York: W.H. Freeman and Company Zilker, I., Holliday, G. M., Fischer, H.E., Kauertz, A., Lederman, J. S. , Lederman, N.G. (August, 2009). Are historical contexts suitable for assessing students‘ competences in the field of nature of science and scientific inquiry? Contemporary science education research: international perspectives. Paper presented at ESERA.

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Chapter 8

SCIENCE EDUCATION THROUGH RESEARCH Katsuhito Kino*, Takanobu Kobayashi, Rie Komori, and Hiroshi Miyazawa Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido, Kagawa 769-2193, Japan

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ABSTRACT The present world is rapidly changing at all times. Students must try hard to adjust themselves to such a world. Here, we showed our previous researches (i. the mechanism of point mutations, ii. the drug discovery using in silico, iii. the study of mouse DNA polymerase alpha, iv. the genetic analysis of biogenetical times) and described the knowledge, the skills and the logic of chemistry and biology required for these researches. Logical thinking and the capability to respond to diverse situations were needed for success. As research is conducted by making full use of a wide range of the researcher‘s ability, students will be able to acquire the capabilities, such as logical thinking and adaptability, through experiences of the research studies. Thus, the education acquired through research will help students to adapt to the rapidly changing world.

1. THE SITUATION TODAY The scientific world is in a state of constant change. With such change occurring at an ever faster rate, students who are only able to learn through textbooks or manuals are *

Correspondence to: Katsuhito Kino, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido, Kagawa 769-2193, Japan Tel: +81-87-894-5111, Fax: +81-87-894-0181, E-mail: [email protected]

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becoming increasingly unable to keep up. As universities are potentially the last chance for students to cultivate themselves to be adaptable to an ever-changing society, it is essential that students acquire the ability to cope with any given situation at university. University lectures have a tendency, however, to be unidirectional, i.e., from one professor to many students. Moreover, the exercises of the course commonly have only unequivocal answers. While the professor must present clear lectures and demonstrate experiments, students‘ incomprehension arises due not only to the teaching style of the professor but also to the passivity of students during the lectures. When students passively participate in the lectures and exercises, the university becomes no more than a place for cramming information into the student‘s brains. In such cases, it becomes harder for students to understand their purpose of learning, thereby hindering their motivation to learn. This in turn prevents students from acquiring the ability to think logically, or the ability to cope well with many situations. As students are currently forced to acquire these abilities during their short period of graduate research, it would not be true to say that professors are providing a proper university education for students. Here, we analyzed the results of previous research carried out by each of the authors, and discussed the knowledge and skills that they needed for conducting the research.

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2. RESEARCH IN THE MECHANISM OF POINT MUTATIONS, AND THE KNOWLEDGE AND SKILLS OBTAINED Like G-to-T point mutations, G-to-C point mutations (Figure 1) can be detected under several oxidation conditions. These mutations have been detected on the ras oncogene and the p53 gene in cancer cells. As one of the oxidative lesions of guanine, 8-oxoG (Figure 2A) causes G-to-T point mutations through adenine incorporation opposite the site of its lesion. However, oxidative lesions of guanine that incorporate guanine on the opposite side had not been previously reported, and the mechanism of G-to-C point mutations was still unclear.

Figure 1. A mechanism of G:C to C:G transversion via guanine oxidation. ‗X‘ indicates a product of guanine oxidation.

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Iz (Figure 2A) is known to be a lesion that forms efficiently from guanine [1-5]. From the viewpoint of the chemical structure, we noticed that an Iz:G base pair could form through hydrogen bonding [2], which was strongly indicated by quantum chemistry calculations (Figure 2B) [2,3]. Upon experiments using DNA polymerase, guanine was selectively incorporated opposite Iz [3-7]. Iz is gradually hydrolyzed to become Oz (Figure 2A) under physical conditions. We demonstrated that guanine is preferentially incorporated opposite Oz by DNA polymerases  and , the major polymerases in DNA replication, suggesting that this was caused by Oz:G base pairing (Figure 2B) [8]. We believe that Oz could be a lesion that induces actual G-to-C point mutations, and that the formation of Oz:G and 8-oxoG:A base pairs might be connected to changes in the ras gene and the onset of cancer in cells.

Figure 2. (A) The products of guanine oxidation. (B) The base pairs of Iz:G and Oz:G.

Without using organic chemistry in our research, we may never have predicted the chemical structure of the base pairs. Moreover, we had to acquire basic knowledge and the skills of quantum chemistry calculations in order to investigate the stability of these base pairs. The knowledge of analytical chemistry and photochemistry was also required for synthesizing the DNA lesions. The basic knowledge and techniques of molecular biology is a prerequisite for experiments using enzymes, and we needed the understanding of reaction kinetics to analyze the association and reactivity of the enzymes. Finally, the knowledge and skills of radiation science were essential for analyzing the enzymatic reaction. The success of this research thus depended on both the acquisition of knowledge from a wide range of fields and the logical repetition of trial and error to acquire technical skills. Particularly for kinetics of enzymatic reactions and quantum chemistry calculations, our understanding was limited from just attending undergraduate lectures, and only through hands-on research we were able to appreciate the significance of these fields. Our experiences show the enormous importance of education through research.

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3. IN SILICO DRUG DEVELOPMENT RESEARCH, AND THE KNOWLEDGE AND SKILLS OBTAINED

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Genomics and proteomics can be utilized to identify genes or proteins associated with diseases and to develop new drugs that target them. The prediction in silico can be used to search for lead compounds that react with the drug target. The reactivity of the target and candidate compound can then be predicted in silico, allowing for more effective design of pharmaceuticals. We have analyzed NF-B, which is activated by various different stimuli such as cytokine and bacterial viruses and is involved in the transcription of various genes governing life processes (Figure 3) [9]. Its importance to the immune system and its relation to cancer have been widely reported, and NF-B inhibitors are expected to be used as potential pharmaceuticals in the treatment of cancers or inflammatory diseases. More than 700 compounds to date have been reported to inhibit NF-B [10], but there are practically no reports of specific NF-B inhibitors. Among the NF-B active pathways, NF-B signaling pathways converge at the stage of DNA binding, and there is high conservation of amino acids among the NF-B family. These findings suggest that an inhibitor that targets the DNA binding domain of NF-B is likely a broad and specific inhibitor. We therefore searched for low molecular compounds that inhibit DNA binding of NF-B to develop novel NF-B inhibitors that could become lead compounds for development of new pharmaceuticals.

Figure 3. The pathway of NF-B activation.

We screened a chemical library for selection of compounds in silico, and discovered the low molecular compound NI241 that inhibits DNA binding of p50 (Figure 4). NI241 analogues also exhibited the same inhibition, and their inhibitory effects were found to be altered by the substituents on the N-phenyl group. We therefore predicted a model for NI241 binding with p50 in silico. In this model, NI241 forms hydrogen bonds with Tyr60, His144, and Asp242 on p50 [11]. To identify the more effective inhibitors, many low molecular compounds are being investigated based on the structure of NI241 and the predicted binding model.

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Figure 4. The structure of NI241.

The use of computer science and in silico modeling, which requires a wide range of knowledge and skills, is becoming increasingly important in research on new pharmaceuticals in order to cut costs and output time. We have made predictions using bioinformatics and docking studies for the selection of possible inhibitors, and have used knowledge and skills of molecular biological techniques for the evaluation of inhibition activity. In future studies, structural improvements using organic chemistry techniques, in silico prediction of effectiveness, and evaluation of activity using molecular biological techniques will all be necessary for discovery of more effective inhibitors.

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4. RESEARCH INTO THE MOUSE DNA POLYMERASE  GENE, AND THE KNOWLEDGE AND SKILLS OBTAINED DNA polymerases , , and  (pol , pol , and pol ) are involved in eukaryote chromosomal DNA replication, and to date they have each been shown to play separate roles. When research was still in its early stages and molecular biological techniques were not as well established as now, isolation and genetic cloning of pol  mutations played an important part in investigating intracellular functions. We were able to yield fruit using isolation and genetic cloning of temperature-sensitive pol  mutants for the following main reasons: 1) 2) 3) 4) 5)

We investigated adequate protocols to achieve our objectives. We carried out experiments in full accordance with the protocols. We did not abandon the research when it did not go as expected. We read many papers to continually consider other methods and techniques. We used the expertise of other researchers for areas in which we lack knowledge— i.e., we proactively carried out collaborative research.

In our research, we were able to isolate a pol α mutant in the following manner. We had to construct a conditionally lethal mutant, as pol  is essential to survival. Following

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treatment with a mutagen, normal cells were died by internal exposure to [3H]thymidine, which is incorporated under high temperature by normal pol , in order to isolate cells in which pol  does not function at high (or nonpermissive) temperature

Figure 5. Artificial translocation. The M6-39 cell is a hybrid clone between RS4729 cell (a human diploid fibroblast line) and tsFT20 (a temperature-sensitive mutant cell line containing heat-labile DNA polymerase , derived from mouse mammary carcinoma FM3A cells), and contains only one or two human chromosomes. Logarithmically growing M6-39 cells were exposed to various doses of irradiation from a 60Co source. After irradiation, the cells were hybridized with tsFT20 in polyethylene glycol 4,000. Temperature-resistant hybrid clones (IRF16, IRF31 cells) were analyzed, and contain small portion of human DNA which reverts heat-labile DNA polymerase  activity.

Cell strains in which DNA synthesis reduced rapidly due to sensitivity to nonpermissive temperature were selected, and we successfully isolated a mutant with temperature-sensitive pol  (tsFT20) following examination of the thermostability of DNA polymerase activity [1214]. Along with some good luck, we were able to achieve this result through theoretically constructed protocols and through complete implementation of these protocols.

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At that time, the pol  protein had yet to be purified, and isolating the gene was more difficult than anyone could possibly imagine nowadays. We attempted to isolate the gene by introducing DNA to mutant clones and then isolating the revertant clones [15]. We built a system of collaborative research with a laboratory that had capabilities in gene-transfer techniques (transfection), but it became clear during the experimental process that tsFT20 is a cell with extremely low transfection efficiency. After achieving no further progress, we discovered a paper describing an experiment in which a mutant cell was fused with cells whose chromosomes had been finely cut up using  rays [16]. We proposed isolating the DNA fragments which make tsFT20 revert using  rays. In our experiments, we fused tsFT20 cells with normal human cells and cultivated them for a short period (Figure 5). Cells in which the number of human chromosomes was reduced to one or two were taken as  rayirradiating cells and were again fused with tsFT20 cells. Cells that could proliferate under nonpermissive temperature conditions were then isolated; this allowed us to identify the region of human genes that causes temperature sensitivity to revert [17]. We named this experiment for ―artificial translocation‖. Another research group eventually published the isolation of the human pol  gene before us [18], but based on parts of the amino acid sequences of purified pol  protein from mouse cells we were able to isolate the mouse pol  gene, including other subunits [19]. We have also demonstrated that the tsFT20 cell is a temperature-sensitive mutant of the pol  catalytic subunit. The temperature sensitivity of the pol  mutant was found to revert through the action of the catalytic pol  subunit gene that we isolated (Figure 6) [20]. From the identification of the mutational site of the tsFT20 cell and the reverted clone, we showed that a region different from the active site is involved in the thermostability of pol . Considering our own experience, as research continually provides new findings, it is essential when conducting scientific research to constantly stay abreast of the latest information through research papers and other researchers.

Figure 6. Summary of mutation sites on a mouse DNA polymerase  catalytic subunit. The bold line represents the polypeptide of catalytic subunit of DNA polymerase . Numbers above the line are amino acids positions. The 7 highly conserved regions in class B DNA polymerases are indicated by black boxes with Roman numerals (I-VII). The five conserved regions in eukaryotic DNA polymerases  proposed by us are indicated by white boxes with letters (A-E). Mutation points of tsFT20 and seven growth revertant cell lines are indicated by the closed triangle and open triangles, respectively.

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5. RESEARCH INVOLVING A GENETIC ANALYSIS OF DEVELOPMENTAL TIME, AND THE KNOWLEDGE AND SKILLS OBTAINED

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The clonal life cycle of Paramecium tetraurelia begins with sexual reproduction and ends with clonal death. During the clonal life, cells undergo unidirectional changes of immaturity, maturity and senescence. Genetic mechanisms are believed to be involved in the timing of phases of the life cycle, but other than the fact that its control is via fission age rather than physical time [21-25], its detailed mechanisms have not been elucidated. A correlation has been shown between a long period of sexual immaturity and a long maximum clonal life span in both mammals [26] and ciliates [27]. We therefore hypothesized that a clone that is slow to reach sexual maturity should exhibit a long life span, and then we attempted to isolate and analyze a mutant with a long period of sexual immaturity. First, we investigated the variability in the immaturity period and the hereditary patterns of wild-type stock, clarifying the standard patterns [28]. We then randomly induced mutations through N-methyl-N‘-nitro-N-nitrosoguanidine (MNNG) treatment and isolated two mutants that exhibited maturity after a completely different time lag from the wild-type strain [29,30]. The results of genetic analysis indicated involvement of a single recessive gene in each case; these were named rie-1 (remote immaturity exit 1) and rie-2. In order to prove our initial hypothesis, we measured the life span of the two clones, and found them to be shorter than the wild-type strain. We also examined offspring from repeated backcrosses with the wild-type strain, finding that even in generations in which the rie+ strain had reverted to a life span similar to that of the wild-type strain, the life span of the rie strain remained shortened. While further research is still needed to clarify the function of the rie gene with respect to life span, these mutant strains of a ciliate are the first to show lengthened time to maturity. We have therefore developed concrete research materials for analyzing the mechanisms regulating the time of clonal development (Figure 7).

Figure 7. Paramecium mutant showed long autogamy immaturity period. Genetic analyses indicated that a single recessive gene, rie (remote immaturity exit), was responsible for the mutant phenotype. The clonal life span was shorter in the rie mutant than in the wild-type.

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In our research, we have isolated mutants with the trait of interest and attempted to clarify the involved mechanism by identifying the causative gene, which may be called the classical method of genetics. Knowledge of both basic genetics and cell biology, as well as that of the particular genetics of Paramecium, are needed. Paramecium is a species of great evolutionary and taxonomic interest when tracing the path of the origin of life, and combining knowledge from evolutionary studies and taxonomy allowed us to analyze it from a wider range of possibilities. Although the experimentation itself is time-consuming as our research involves the analysis of the life cycle, close observation of organisms can lead to successive interests, allowing us to approach continued research freely.

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6. THE SIGNIFICANCE OF EDUCATION THROUGH RESEARCH We discussed our actual research, focusing on the types of learning and techniques that are necessary for successful research. Research requires cutting-edge knowledge, and researchers have to examine all the facts currently known. These researchers should therefore be sufficiently capable to provide students with the applicable skills, logical thinking ability, and learning perspectives necessary for flexible adaptability to the rapidly changing research environment. In contrast, educators not involved in research may be less able to provide the proper university education. Since researchers can directly instill applications, logic and basic learning in students, it is essential that students belong to laboratories and conduct research in their first year of university. Students who begin research early will have more opportunities to learn the basic knowledge they need and to appreciate the significance and perspectives of different areas of study. Students are thus likely to become more aware of the significance of their lectures, thereby increasing their motivation to learn. Conducting research and experiments for which the outcome is unknown requires the ability to cope with novel situations and to think logically, which allows students to cultivate these abilities naturally. Discussions in the laboratory between students and researchers have the educational effect of correcting misguided research objectives or misunderstandings of information. Students can also acquire broader perspectives and applied skills by circulating between different laboratories, rather than remaining in only one assigned laboratory. Implementing such a system would help students acquire more viewpoints and composite abilities from different supervisors, allowing them to cope with the rapid changes in research today.

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Cadet, J., Berger, M., Buchko, G. W., Joshi, P. C., Raoul, S., Ravanat, J.-L. (1994) 2,2Diamino-4-[(3,5-di-O-acetyl-2-deoxy--D-erythro-pentofuranosyl) amino]-5-(2H)oxazolone: a novel and predominant radical oxidation product of 3',5'-di-O-acetyl-2'deoxyguanosine. J. Am. Chem. Soc. 116, 7403-7404.

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Katsuhito Kino, Takanobu Kobayashi, Rie Komori, et al. Kino, K., Saito, I., Sugiyama, H. (1998) Product analysis of GG-specific photooxidation of DNA via electron transfer: 2-Aminoimidazolone as a major guanine oxidation product. J. Am. Chem. Soc. 120, 7373-7374. Kino, K. & Sugiyama, H. (2001) Possible cause of G:C->C:G transversion mutation by guanine oxidation product, imidazolone. Chem. Biol. 8, 369-378. Kino, K., Miyazawa, H., Sugiyama, H. (2007) User-friendly synthesis and photoirradiation of a flavin-linked oligomer. Genes Environment. 29, 23-27. Kino, K., Kobayashi, T., Arima, E., Komori, R., Kobayashi, T., Miyazawa, H. (2009) Photoirradiation products of flavin derivatives, and the effects of photooxidation on guanine. Bioorg. Med. Chem. Lett. 19, 2070-2074. Kino, K. & Sugiyama, H. (2005) UVR-induced G-C to C-G transversions from oxidative DNA damage. Mutat. Res. 571, 33-42. Kino, K., Sugiyama, H., Miyazawa, H. (2008) Chapter X: Molecular basis of guanine oxidation under UV-A/VIS radiation and its biological effects. Progress in DNA Damage Research. (Miura, S., Nakano, S., Eds) Hauppauge NY: Nova Science Publishers., pp. 271-276. Kino, K., Sugasawa, K., Mizuno, T., Bando, T., Sugiyama, H., Akita, M., Miyazawa, H., Hanaoka, F. (2009) Eukaryotic DNA polymerases ,  and  incorporate guanine opposite 2,2,4-triamino-5(2H)-oxazolone. ChemBioChem 10, 2613-2616. Hayden, M. S. & Ghosh, S. (2004) Signaling to NF-B. Genes Dev. 18, 2195-2224. Gilmore, T. D. & Herscovitch, M. (2006) Inhibitors of NF-B signaling: 785 and counting. Oncogene 25, 6887-6899. Kobayashi, T., Yoshimori, A., Kino, K., Komori, R., Miyazawa, H., Tanuma, S. (2009) A new small molecule that directly inhibits the DNA binding of NF-B. Bioorg. Med. Chem. 17, 5293-5297. Murakami, Y., Yasuda, H., Miyazawa, H., Hanaoka, F. and Yamada, M. (1985). Characterization of a temperature-sensitive mutant of mouse FM3A cells defective in DNA replication. Proc. Natl. Acad. Sci. USA 82, 1761-1765. Murakami, Y., Eki, T., Miyazawa, H., Enomoto, T., Hanaoka, F. and Yamada, M. (1986). Further characterization of a murine temperature-sensitive mutant, tsFT20 strain, containing heat-labile DNA polymerase -activity. Exp. Cell Res. 163, 135-142. Hanaoka, F., Tandai, M., Miyazawa, H., Murakami, Y., Hori, T. and Yamada, M. (1984). Human DNA polymerase : Compensation for heat-labile mouse DNA polymerase  and its gene localization on the X chromosome. Mol. Biol. Med. 2, 323335. Wigler, M., Silverstein, S., Lee, L.-S., Pellicer, A., Cheng, Y., Axel, R. (1977). Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell 11, 223232 Cirullo, R. E., Dana, S., Wasmuth, J. J. (1983) Efficient procedure for transferring specific human genes into Chinese hamster cell mutants: interspecific transfer of the human genes encoding leucyl- and asparaginyl-tRNA synthetases. Mol. Cell. Biol. 3, 892-902. Miyazawa, H., Tandai, M., Hanaoka, F., Yamada, M.-a., Hori, T., Shimizu, K. and Sekiguchi, M. (1986). Identification of a DNA segment containing the human DNA polymerase  gene. Biochem. Biophys. Res. Commun. 13, 637-643.

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[18] Wong, S.W., Wahl, A.F , Yuan, P.M., Arai, N., Pearson, B.E., Arai, K., Korn, D., Hunkapiller, M.W., Wang, T.S. (1988) Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 7, 37-47. [19] Miyazawa, H., Izumi, M., Tada, S., Takada, R., Masutani, M., Ui, M. and Hanaoka, F. (1993) Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase -primase complex and their gene expression during cell proliferation and the cell cycle. J. Biol. Chem. 268, 8111-8122. [20] Izumi, M., Miyazawa, H., Harakawa, S., Yatagai, F. and Hanaoka, F. (1994) Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase  from a temperature-sensitive mouse FM3A cell line. J. Biol. Chem. 269, 7639-7644. [21] Kroll, R. J. & Barnett, A. (1968) The effect of different fission rates on the onset of maturity in Paramecium multimicronucleatum. J. Protozool. 15 (Suppl.), 10. [22] Takagi, Y. (1970) Expression of the mating-type trait in the clonal life history after conjugation in Paramecium multimicronucleatum and Paramecium caudatum. Jpn. I. Genet. 45, 11-21. [23] Smith-Sonneborn, J. & Reed, J. C. (1976) Calendar life-span versus fission life-span of Paramecium aurelia. J. Gerontol. 31, 2-7. [24] Takagi, Y. & Yoshida, M. (1980) Clonal death associated with the number of fissions in Paramecium caudatum. J. Cell Sci. 41, 177-191. [25] Takagi, Y., Nobuoka, T., Doi, M. (1987) Clonal lifespan of Paramecium tetraurelia: effect of selection on its extension and use of fissions for its determination. J. Cell Sci. 88, 129-138. [26] Cutler, R. G. (1978) Evolutionary biology of senescence. The Biology of Aging. (Behnke, J. A., Finch, C. E., Moment, G. B., Eds) New York: Plenum Press., pp. 311360. [27] Smith-Sonneborn, J. (1981) Genetics and aging in protozoa. Int. Rev. Cytol. 73, 319354. [28] Komori, R., Harumoto, T., Fujisawa, H., Takagi, Y. (2002) Variability of autogamymaturation pattern in genetically identical populations of Paramecium tetraurelia. Zool. Sci. 19, 1245-1249. [29] Komori, R., Harumoto, T., Fujisawa, H., Takagi, Y. (2004) A Paramecium tetraurelia mutant that has long autogamy immaturity period and short clonal life span. Mech. of Ageing Dev. 125, 603-613. [30] Komori, R., Sato, H., Harumoto, T., Takagi, Y. (2005) A new mutation in the timing of autogamy in Paramecium tetraurelia. Mech. of Ageing Dev. 126, 752-759.

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In: Science Education in a Rapidly Changing World Editor: Seth D. Grahame

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Chapter 9

SCIENCE AND TECHNOLOGY MUSEUMS AS PLACES FOR CRITICAL THINKING SKILL DEVELOPMENT Kristin Knipfer and Daniel Wessel* Knowledge Media Research Center, Tuebingen, Germany

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ABSTRACT Based on our experience in the field of psychological research in museums, with the two focal points of supporting critical thinking and the potentials of mobile devices, we argue that critical thinking – a crucial skill in our rapidly changing world – can and should be supported in informal settings such as science museums by means of mobile devices: As our world is rapidly changing, the lay public is required to inform themselves about contemporary socio-scientific issues constantly throughout life to make deliberative decisions as participants of our democratic knowledge society. For reflective judgment, critical thinking skills are essential. However, respective abilities and dispositions are often lacking, and therefore developing critical thinking skills is one of the desired outcomes of modern science education. We argue that science museums are an excellent setting for skill development: They present sufficient information serving as a basis for reflective judgment and critical thinking if visitors are supported in activities such as the evaluation of opposing arguments and integration of controversial information. This support can easily be accomplished by tapping into the potential of visitors‘ personal mobile devices. By offering tools that facilitate the fundamental cognitive processes of critical thinking, visitors‘ reflective judgment is supported during their visit. If the tools are available on the visitors‘ personal devices (e.g., cellphones), they could access the tool again at any time in their daily life. As an illustration for this argument, we present a design draft of such a tool, which is based on current psychological knowledge about critical thinking and reflective judgment, and we outline its specific potential for critical thinking skill development in informal settings.

* Both authors contributed equally to this work.

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Kristin Knipfer and Daniel Wessel Silver nanoparticles could be key to devices that keep hearts beating strong1 New fibre nanogenerators could lead to electric clothes 'Fertility chip' to accurately count spermatozoa in sperm Report highlights nanotech retreat Stem cell capsules may help mend broken bones EPA SAP releases report on nanosilver and other nanometal pesticide products

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Dangerous Nanoparticles Can be Transported by Insects

Our world is rapidly changing. This truism is part of the topic of this book and can be seen in multiple areas, perhaps most strikingly in the rate of technological development and the ease of global communication. While scientific articles are still published in traditional print media, the internet has allowed lay people almost unlimited access to scientific information: Reports in online newspapers or other public media sites, contributions in discussion forums, blogs or mailing lists, advertisement on corporate websites – these are some of the many ways we are confronted with scientific information today. The headlines at the beginning of this chapter are only a short excerpt of results from a news search that covered news about nanotechnological research released solely in February 2010. This illustrates strikingly the scientific information load we are confronted with daily. What is also illustrated by these headlines is the disagreement among scientific experts with respect to the prospects and risks of nanotechnology. This is true not only for the topic of nanotechnology but for nearly all contemporary scientific issues – think of the worldwide climate change discussion or the debate on genetically modified food. This is not new of course – it is the very nature of science – but today, the lay public has far more insight into current research than ever before. On the one hand, this is, of course, desirable as in our democratic knowledge society, the lay public has to be able to inform themselves to make deliberate decisions: For example, which political party acts in one‘s own best interest, whether or not to buy products with nanotechnological components or genetically modified food, or whether or not to inoculate oneself against a particular flu strain. These decisions require a basic understanding of how scientific innovations might improve or endanger our daily lives. On the other hand, lay people must be able to deal with scientific information adequately. Given contradicting information, it is not enough to merely learn facts and figures about scientific issues. The information we are confronted with is seldom objective or certain: Various actors (scientists, businessmen, politicians, media outlets, etc.) with competing perspectives and arguments are involved in the public debate (Oulton, Dillon, & Grace, 2004). We thus cannot accept this information as facts but must assume that in most cases they are biased by personal interests or beliefs of the proponents. The scientific and the public debate are therefore closely intertwined. Additionally, information on hot topics that was ―news‖ on one day might be ―water under the bridge‖ the next day. Moreover, scientific 1

Retrieved from http://www.nanotech-now.com/current-months-news.htm

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innovations might have moral and ethical implications (cp. the debate on genetic engineering), which raises questions beyond scientific results. The lay people need to be able to analyze and evaluate the information they encounter, deal sensibly with moral and ethical implications of contemporary scientific topics, and understand the interrelationships inherent among these issues (Oulton et al., 2004; Zeidler, 1984) — in short, they must be able to think critically in order to be reflective practitioners in our rapidly changing world (cf. Norman, 1993; Scardamalia & Bereiter, 2006). While critical thinking is a desired outcome of school education and an often-stated goal of teachers and principals, the actual ability to think critically is often insufficient. Many studies show that people, children and adults, lack critical thinking skills, including even university students (cf. Knipfer & Wessel, 2010). When it comes to evaluating scientific claims and statements concerning science issues under discussion, we must assume that both the lack of meta-knowledge about science and the poor understanding of critical thinking itself impair the ability to think critically. This raises the question of how to support people in critical thinking. In general, critical thinking skills and the individual disposition towards critical thinking are considered to be open to educational influence, especially if the intervention is contextually bound (Brown, 1997). What we find to be needed is a setting that is visited by adults and children alike, that is positively associated with learning, and which allows for pedagogical interventions. We think that science and technology museums fulfill these requirements: While museums are often associated with factual displays of scientific ―facts‖, they are important contributors of science communication of contemporary science today (cf. Boyd, 1999; Institute for Learning Innovation, 2007; Rodari & Merzagora, 2007). They also increasingly offer opportunities to engage in contemporary debates centered around scientific innovations (e.g., ―A Question of Truth‖ by The Ontario Science Center or ―Mine Games‖ by Vancouver‘s Science World, see Wake & Bradburne, 1994; cf. also the project ―NanoDialogue‖ of the European Commission). In 2007, critical thinking was even the main topic of a special issue of the Journal of Museum Education (Shulman-Herz, 2007). Contributions in this journal issue reflect the need to stimulate visitors to ―look closely, wonder and question, make interpretations and form hypotheses based on evidence; make connections to things they already know; consider different perspectives and viewpoints; delve below the surface to uncover complexity; and form conclusions‖ (Ritchhart, 2007, p. 139). Preliminary steps have been made to refine the conceptualization of critical thinking for science and technology museums (for a review of relevant research and a working definition see Knipfer and Wessel, 2010). Indeed, museums are a perfect place to encourage and support critical thinking as they are experienced as being neutral in debates and can inform the public debate by presenting basic scientific facts and figures (Calcagnini, 2007). However, supporting the skill development of critical thinking in museums is no easy feat. Museum research tells us that visitors typically view only 20-40% of an exhibition and follow a wide-but-shallow rather than a narrow-but-deep learning mode (Rounds, 2004) and spend only a short time at an exhibit (cf. ―hurried visitor phenomenon‖, Rounds, 1999; ―all-you-can-eat buffet‖, Hsi & Fait, 2005; ―cultural window-shopping‖, Treinen, 1988) and in the museum itself (cf. ―museum fatigue‖, Davey, 2005). We must assume that visitors do not automatically show critical thinking in museums, and that the support of critical thinking must consider the high

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degree of self-regulation (e.g., goal-setting, information selection, and elaboration strategies) during a museum visit. In an earlier paper (Knipfer & Wessel, 2010), we have outlined four categories for supporting critical thinking in museums:

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1. 2. 3. 4.

Deliberate design of exhibitions that elicit critical thinking Implementation of interactive exhibits to foster critical thinking Augmentation of ―traditional‖ exhibitions to support critical thinking The museum as host of events to elicit critical thinking

We focus here on the augmentation aspect, as it seems to us to be the most promising and widely applicable way to support critical thinking in museums. The augmentation of museum exhibitions can be accomplished without any changes to the present exhibition design and is therefore a quite flexible and economical way. Visitors‘ own mobile devices can be used to support critical thinking, consequently minimizing the needed technical and financial resources. The potentials (and challenges) of mobile devices for museums have already been summarized and discussed by Wessel and Mayr (2007). Mobile devices (esp. mobile phones) have become increasingly powerful, and their potential for education purposes has long been recognized (cf. Horizon Reports of 2006, 2007, 2008, 2009, 2010). Mobile devices are as mobile as the visitors themselves; they are immediately available in front of every exhibit, even in a shared setting like the museum; it is a personal device, which allows for assisting visitors in individual cognitive processes. The specific potentials for supporting critical thinking include that the cognitive processes of critical thinking, such as the evaluation of arguments or weighing alternatives, are made ―visible‖ by means of the users‘ actions on the mobile device. Consequently, it is possible to monitor visitors‘ cognitive processes and scaffold further actions. Both scaffolding during the process and feedback on outcomes of critical thinking might be given based on this information. But what exactly might a ―critical thinking app‖ look like? We used our definition of critical thinking (Knipfer & Wessel, 2010) as the basis for the design of an innovative application for the iPhone/iPod touch: Our definition specifies the relevant cognitive process of critical thinking and describes in detail the desired outcomes of critical thinking in a museum setting. The envisioned application is to be used in a laboratory exhibition about adiposity, a topic which might elicit strong prejudices that might bias critical thinking about the reasons for the adiposity of a specific person. The exhibition itself provides information about adiposity in general, its causes and influences. Its primary aim is to convey information just like most museum exhibitions. The mobile device, however, provides a concrete case study about an obese person, to which the information of the exhibition may be applied in order to identify the causes of this specific person‘s obesity. Hereby, the device functions in a double role: First, it provides a case study with information about a specific (fictional) person, which functions as evidence for or against specific hypotheses about causes of obesity. Second, both hypotheses presented in the exhibition and the evidence found in the history of the specific case can be integrated by means of the critical thinking application. It allows for connecting hypotheses with evidence, evaluating the strength and direction of the evidence for the found hypotheses, and presenting the hypotheses and their supporting or contradicting evidence in a well-arranged way. This should help to determine the likelihood of the different hypotheses as the ―real‖ causes for the sample case‘s obesity. The mobile

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application works as a ―mediator‖ between the general information of the exhibition and the specific case study. It assists in the careful consideration of evidence in the process of decision-making with regard to the causes of obesity. Given that the process of critical thinking is externalized in the data on the mobile device, we also thought about giving feedback via the mobile device. Visitors can be assisted with generating hypotheses, collecting evidence, weighting evidence, and the unbiased integration of this information to come to a reflective conclusion. It might, for example, alert visitors to information within the exhibition which they have not yet considered, thereby overcoming likely biases in information search and evaluation (e.g., confirmation bias, Nickerson, 1998) and facilitating the inquiry of information independent of prior beliefs and prejudices. Visitors might also be encouraged to share their decisions and their underlying reasons, which might foster knowledge of and respect for opposing views (see e.g., Knipfer, 2009). All the proposed functionalities together should lead to a well-founded personal conclusion about the issue under consideration, even with a highly prejudiced topic such as adiposity. Figure 1 shows two preliminary interfaces of the application.

Figure 1. The left envisioned interface shows how hypotheses and evidence from the case study can be integrated and evaluated; the right envisioned interface illustrates how connections between hypotheses and evidence from the case study are fed back to the user.

Given that the tool makes the process of critical thinking traceable for the visitor, we expect that critical thinking skill development, and especially acquisition of meta-knowledge about critical thinking, can be supported this way, within and perhaps even beyond the museum setting. This is assisted by the availability of the tool on the visitor‘s own mobile device, meaning that in contrast to much of the information provided by exhibitions, visitors can take the tool with them. If evidence and hypotheses are entered manually, it can be separated from the concrete topic and used for any topic. In short, while critical thinking would be trained first within the context of an exhibition, this support could fade out over

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time and leave visitors with the skills and knowledge to think critically about current socioscientific topics. In this commentary, we argued for the significance of critical thinking for science education in our rapidly changing world. We further argued for science and technology museums to contribute to critical thinking skill development, as they are major contributors in communicating rising issues in science and technology. An example for a mobile application to support critical thinking in museums illustrates how critical thinking can be supported in a museum – even if the exhibition was not designed to do so. Although this application was designed for an exhibition about adiposity, the design considerations can be transferred to many other socio-scientific issues, for example, nanotechnology or gene technology. As with any intervention, this and other applications must be analyzed regarding their effect on critical thinking (for evaluation criteria see Knipfer & Wessel, 2010). We are, however, confident that supporting critical thinking in informal settings such as museums is not only possible and desirable but also effective. Science and technology museums might thus take a more active role in critical thinking skill development in the future.

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REFERENCES Boyd, W. L. (1999). Museums as centers for controversy. Daedalus, Journal of the American Academy of Arts and Sciences, America‘s Museums, 128(3), 185-228. Brown, A. (1997). Transforming schools into communities of thinking and learning about serious matters. American Psychologist, 52(4), 399–413. Calcagnini, S. (2007). Debating as an educational method to science and citizenship. Journal of Science Communication, 6(3). Retrieved from http://jcom.sissa.it/archive/06/03/ JCOM0603(2007)C08 Davey, G. (2005). What is museum fatigue? Visitor Studies Today, 8, 17-21. The New Media Consortium and EDUCAUSE Learning Initiative (2006). The Horizon Report. Retrieved from http://www.nmc.org/pdf/2006_Horizon_Report.pdf. The New Media Consortium and EDUCAUSE Learning Initiative (2007). The Horizon Report. Retrieved from http://www.nmc.org/pdf/2007_Horizon_Report.pdf. The New Media Consortium and EDUCAUSE Learning Initiative (2008). The Horizon Report. Retrieved from http://www.nmc.org/pdf/2008-Horizon-Report.pdf. The New Media Consortium and EDUCAUSE Learning Initiative (2009). The Horizon Report. Retrieved from http://www.nmc.org/pdf/2009-Horizon-Report.pdf. The New Media Consortium and EDUCAUSE Learning Initiative (2010). The Horizon Report. Retrieved from http://www.nmc.org/pdf/2010-Horizon-Report.pdf. Hsi, S., & Fait, H. (2005). RFID: Tagging the world. RFID enhances visitors' museum experience at the Exploratorium. Communications of the Association for Computing Machinery, 48(9), 4-37. Institute for Learning Innovation (2007). Evaluation of learning in informal learning environments. Learning science in informal environments: Commissioned paper. Retrieved from http://www7.nationalacademies.org/bose/InstituteforLearning Innovation Commissioned_Paper.pdf

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Knipfer, K. (2009). Pro or con nanotechnology? Support for critical thinking and reflective judgement at science museums (Doctoral thesis, University of Tuebingen, Germany) Retrieved from http://tobias-lib.ub.uni-tuebingende/volltexte/2009/3761/pdf/Knipfer Kristin.pdf. Knipfer, K., & Wessel, D. (2010). Critical Thinking and Reflective Judgment in Science and Technology Museums: The Art of Intellectual Engagement. Manuscript submitted for publication. Nickerson, R. S. (1998). Confirmation bias: A ubiquitous phenomenon in many guises. Review of General Psychology, 2, 175-220. Norman, D. (1993). Things That Make Us Smart. Addison Wesley Publishing Company. Oulton, G., Dillon, J., & Grace, M. M. (2004). Reconceptualising the teaching of controversial issues. International Journal of Science Education, 26, 411-423. Ritchhart, R. (2007). Cultivating a culture of thinking in museums. Journal of Museum Education, 32(2), 137-154. Rodari, P., & Merzagora, M. (2007). Comment: The role of science centres and museums in the dialogue between science and society. Journal of Science Communication, 6(2), Retrieved from http://jcom.sissa.it/archive/06/02/Jcom0602(2007)C01/Jcom0602(2007) C01.pdf Rounds, J. (Ed.). (1999). Making meaning in exhibits [Special Issue]. Exhibitionist, 18(2). Rounds, J. (2004). Strategies for the curiosity-driven museum visitor. Curator, 47(4), 389412. Scardamalia, M., & Bereiter, C. (2006). Knowledge building: Theory, pedagogy, and technology. In K. Sawyer (Ed.), The Cambridge handbook of the learning sciences. New York: Cambridge University Press. Shulman Herz, R. (2007). Critical thinking skills in the museum. Journal of Museum Education, 32(2), 95-99. Treinen, H. (1988, March) Zwei Aspekte des Museumswesens: Das Museum als Kulturträger und Massenmedium [Two aspects of the modern museum: The museum as an institution of culture and as an instrument of mass communication]. Paper presented at the 17th International SIBMAS Congress, Mannheim, Germany. Retrieved from http://www. sibmas.org/congresses/sibmas88/mannheim1988_05.html Wake, D. A., & Bradburne, J. M. (1994). Mine Games: The science centre as social forum. Retrieved from http://www.bradburne.org/downloads/exhibitions/MineGamesWEB.pdf Wessel, D., & Mayr, E. (2007). Potentials and challenges of mobile media in museums. International Journal of Interactive Mobile Technologies, 1(1), 32-39. Zeidler, D. L. (1984). Moral issues and social policy in science education: Closing the literacy gap. Science Education, 68, 411-419.

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In: Science Education in a Rapidly Changing World Editor: Seth D. Grahame

ISBN 978-1-61728-914-9 © 2011 Nova Science Publishers, Inc.

Chapter 10

QUALITY MANAGMENT FOR SCIENCE EDUCATION Teodora Ruginosu¹ and Sezgin Ersoy² ¹ NGO Formare Studia Martha Street no 8A, Iasi Romania ² Marmara University Technology Faculty Mechatronics Department Istanbul Turkey

1. QUALITY IN EDUCATION

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Quality of services offered by an educational institution represents all the features of a study program and its provider, through which the beneficiary‘s expectations are met, as well as the quality standards. The quality of an educational institution is determined by the quality of the educational services (Fulfilment of customers‘ demands: External and Internal) and processes offered by it (Use of resources, Procedures, Information, Organization of processes). Any organization that provides educational services, when proposes building the quality assurance system of the educational services starts from a set of guiding principles that will base specific criteria, standards, indicators and procedures. The quality of an educational institution is Determined by the quality of the educational services (Fulfillment of customers' demands: External and Internal) and processes offered by it (use of resources, Procedures, Information, Organization of processes). Quality Of The Organization depends on organizational culture, structure, systems, facilities, management, human resources. Quality education has the following characteristics:      

It is based on innovation and diversity; It is offered by responsible institutions; It is promoted by educational leaders; Respects individual autonomy and is based on institutional autonomy; It is result oriented; It is made through dialogue and partnership;

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  

It is centred on customers and beneficiaries of educational services; Assures the participation of educational actors and valorises the human resource; Understands the interdependence between suppliers and recipients involved in the educational offer.

A key role in generating quality at the institutional level it has the implementation of a dynamic management, appropriate to the objectives and socio-economic context. Regardless of size, structure or maturity of an educational organization, it needs to establish an adequate management framework in order to have success. International Standards Organization (ISO) defines quality as being set of characteristics of an entity (product, activity, process, organization etc.) that confer to that entity the ability to satisfy expressed and implicit needs. These objectives are achieved by the educational institution through teaching, educational activities, scientific research and various other activities of educational institution In an environment of rapid change as the present world, the educational organizations must be agile, flexible, must respond rapidly to the needs and expectations (in constant change) of the stakeholders. Therefore educational organizations must measure, anticipate the needs and expectations of stakeholders, must monitor their experiences and perceptions, must monitor and analyze the performance of other competitive organizations. Information should be gathered from both, present and future, interested parties. This information will be used to establish, implement and review the policies, strategies, objectives, targets, measures on short, medium or long term, will help organizations to develop and to achieve a balanced set of results regarding stakeholders. Organizations must identify and understand the required skills both present and future, in order to implement its policies, strategies, objectives and plans. They recruit their staff and train it or develop it to achieve the desired skills. Through promoting and supporting the development of their employees, the organizations ensure the staff awareness and recognition, their will to use their full potential, their will and preparation to adapt to changes, both in terms of organizational change and personal capabilities. Staff should be encouraged to look ahead and beyond present capabilities, to seek opportunities for innovation and continuous improvement that adds value. Full involvement of staff will help generate and implement ideas for improvement. Organizations must continually learn, both from their own operations and from others. They must rigorously compare performance, both internally and externally. They need to capture and share knowledge of staff, to the best use of learning throughout the organization. There must be an opening in the acceptance and use of ideas from all stakeholders. Organizations must adopt a highly ethical approach, must be transparent and accountable, to stakeholders, for their performance as responsible organizations, socially speaking. They must pay attention to their social responsibility and environmental protection and to promote them actively supported both now and in the future.

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2. TRENDS AND DEVELOPMENTS IN THE WORLD The educational system of each country has its own peculiarities caused by economic, social, political, cultural and civilization level of society, specific traditions of a nation and teaching concepts which they promote. Each country builds a level corresponding to the specific education and degree development, and expectations and requirements for education and training of future generations. The diversity of education systems everywhere does not prevent us to see common features and some general trends of evolution and development. Worldwide, there is the primary requirement that education systems must begin, continue and sustain the social changes and progress, ensuring quality education, preparing the individual for the future, developing its ability to adapt to scientific and technical change and innovate. From this perspective, educational systems suffer further adjustments, recording following trends, confirmed at universal scale:  

  

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    

   

The raising of social prestige of vocational education and expression trend of its merger with general education; Creating more opportunities to assert many talents and interests of young people, through growth and diversification of optional and alternative education, especially after age 16 years; Increasingly rapid integration of new technologies in education (teacher versus TV, the Internet, etc). Adopting effective measures for social integration and qualification of youngsters leaving early the school system [1] Creating a "balance between different specializations: Humanities, Science, Technology and Professional; The tendency of ―non specialization‖, completed in "groupings of training programs, aiming at creating a set of common skills used in more trades; Creating an "open system of admission to higher education" Providing initial training of all teachers in University courses for at least three years; Considering the initial and ongoing training 'as a whole [2] The opening of school to community social problems "to overcome underlying causes of uncertainty and bottlenecks experienced by the education systems" [3] and a deeper involvement of these environments (family, local, church, children and youth organizations, associations) in school issues; The democratization and reform of "structures in compulsory education‖ [4] The compatibility of national systems of higher education in Europe, a recommendation that has become imperative especially for EU candidate countries; The transition from teacher-centred education to learning centred on pupil and student; The approximation, up to identification, of the special education with normal education and expansion of integrated and inclusive education, breaking the barriers regarding the access of these types of youngsters to higher forms of education and training, through the following actions: the special education system to work towards its integration into regular education and schools in the normal education system must be prepared to receive and integrate children from special education.

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3. EFFECTS OF QUALITY IN EDUCATION Implementing a quality management leads to institutional change and development. Quality management system ensures the quality and future development of all school activities: teaching and studying, learning activities, assessment activities, European/International politics, administrative and managerial functions, relationships in school. Quality management includes evaluation and accreditation and all actions and mechanisms by which the quality of education is maintained and developed. The existence of quality management allows the school to learn about itself, to make changes and improvements where necessary, to interact effectively with national and international external environment. Training has shown that compared with the variety of objectives, learning tasks, learning and teaching styles, the possibilities of combining the elements of teaching process, with operations to be carried out, there may be a variety of methods, troubleshooting , processes, techniques used by teachers and students. So there is a plurality of teaching methods that can be properly and when necessary by well trained teachers that are creative, are opened to computer information technology and dedicated to teaching.

4. CONCLUSION

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The role / duties of employees in implementing a quality management in organizations providing educational services:     

to know the policies of the organization, mission and vision. to know its resources, but also the constraints facing the organization. to know the expectations of the management team regarding them. To be prepared according to requirements of the job they occupy. To train themselves continuously for being up to date with the news and to respond to different learning styles through the diversification of methods, by multiplying the processes, by combining various methods and procedures, by reporting them to the specific situations, through constant research and information updated, by using computer technology (ICT).

How can employees be involved in services quality assurance?     

by putting his ideas in the service organization; by respecting the quality procedures at organization level; by using new and attractive methods in activities with target group; by notifying the management team on the competences acquired after the date of employment; by knowing the responsibilities of superiors in order to address to the right person depending on the type of problem they may face (to address to the principal is not always the best solution);

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by promoting the organization‘s actions to attract beneficiaries; by announcing the results of his operations; by showing loyalty, honesty, credibility. by building partnerships with other organizations for learning.

REFERENCES [1]

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[2] [3] [4]

Measures taken in European Union Member States for those who have left the education system without qualification ", 1997 Education in other countries", 1990, pp 7-14, 41, 64, 83 Dictionnaire encyclopedique de l‘education et de la formation", 1996, pp 959-963 Continuous training of teachers in the European Union and the Member States of EFTA / EEA, 1997, p. 7.

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INDEX

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A absorption, 24 abstraction, 48, 55 accountability, 66, 90 accreditation, 148 acid, vii, 1, 3, 4, 5, 6, 9, 14, 21, 23, 24, 28, 131 acquisition of knowledge, 127 active site, 131 acute infection, vii, 1 acute leukemia, 24 adaptability, x, xi, 87, 125, 133 adaptation, 82, 90, 91, 97 adenine, 126 adiposity, 140, 142 adult T-cell, 5 adulthood, 83 advantages, 81, 93 advocacy, 49 agencies, 63, 65, 67, 70 aggression, 84 AIDS, viii, 31 alanine, 5 albumin, 7, 8, 10, 11, 14, 15, 25 alertness, 50, 59, 60 algorithm, 50, 53, 54 ambient air, 11 amino acids, 22, 128, 131 ammonia, 4, 23 anatomy, 65 anesthesiologist, 6 angina, 19 angiogenesis, 16, 18 angiography, 14, 18 angiotensin II, viii, 2, 28 animations, 90, 92, 93 antibiotic, 23, 24

anti-cancer, 25 anticancer drug, vii, 2, 17, 21, 22 antigenicity, 7 antioxidant, 20 antitumor, 3, 6, 7, 10, 19, 20, 21, 23, 24, 25, 26, 28, 29 antitumor agent, 21, 25, 26 anxiety, 31, 50, 59 apoptosis, 29 architecture, 18, 27, 56 arginine, 17, 28 arteries, 10 artery, 7, 8, 9, 14, 15, 21, 24 ascites, 9, 27 aseptic, 41 Asia, 98 assessment, x, 88, 109, 120, 122, 148 attachment, 5 authors, 34, 36, 63, 67, 68, 69, 126, 137 automation, 56 autonomy, 111, 145

B background, 42, 89, 107, 113 bacteria, 10, 11, 13, 17, 25, 38 bacterial infection, vii, 1, 2, 12, 13, 16 Bangladesh, 11 barriers, 34, 46, 77, 82, 147 base pair, 127 behaviorists, 91 behaviors, 46, 91, 98, 111, 119 Belgium, 37 benchmarks, 82 bias, 44, 140, 143 bicarbonate, 6 bilirubin, 20, 29 biliverdin, 20

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Index

152 biochemistry, 2, 7 bioinformatics, 129 biological activity, 3 biosafety, 40 bioterrorism, 72 blades, 41 blogs, 138 blood flow, 18, 28 blood plasma, 2, 8 blood pressure, viii, 2, 18, 26, 27 blood transfusion, 8 blood vessels, 8, 10, 16, 18 blood-brain barrier, 7 body fluid, viii, 31, 33, 40, 41, 43 bombing, 63 bonds, 4, 23 bone, 10, 27 bone marrow, 10, 27 bones, xi, 138 bradykinin, vii, 2, 10, 11, 13, 16, 17, 26, 27, 30 brain, 7, 21, 24 brain tumor, 7, 21, 24 brainstorming, 120 breakdown, 23 bridges, 5 Britain, 84

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C cancer, vii, 2, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 20, 23, 25, 26, 27, 28, 126, 127, 128 cancer cells, 13, 20, 126 candidates, 90, 93 carcinogen, 13, 26 carcinogenesis, vii, 1, 13, 26 carcinoma, 130 career development, x, 87 case study, 59, 98, 121, 140, 141 catastrophes, 64 category a, ix, 62 cell cycle, 135 cell line, 22, 23, 130, 131, 135 cell lines, 22, 131 challenges, 69, 70, 72, 76, 81, 82, 140, 143 chemotherapy, 4, 12, 19, 24, 25, 26, 28 chicken, 3, 14 childcare, 79 childhood, 122 China, 17, 18, 34, 36, 43 chlorophyll, 20 chromatography, 3 chronic myelogenous, 20 chunking, 51 chymotrypsin, 4

circulation, 7, 18, 19, 20 citizenship, 142 City, 15, 17, 44, 63 civilization, 147 classroom, x, 65, 79, 87, 94, 95, 107, 110, 111, 112, 114, 115, 119, 120, 121, 122, 123 classroom management, 111, 115 cleaning, 32, 33, 38, 39, 41, 123 cleavage, 11 clients, 41 climate, 41, 138 climate change, 138 clinical oncology, 6 clone, 22, 130, 131, 132 cloning, 129, 135 code generation, 53 coding, 30, 116 cognition, 77, 80, 83, 101 cognitive ability, 80 cognitive development, 49 cognitive flexibility, 56 cognitive load, 56, 58, 60, 77 cognitive process, xi, 48, 58, 137, 140 cognitive psychology, 52 cognitive science, 84 college students, 50, 58 colleges, x, 50, 87 colon, 10, 27 colonization, 33, 45 colorectal cancer, 30 communication, ix, 75, 76, 82, 84, 90, 92, 93, 94, 97, 138, 139 community, ix, 21, 35, 44, 62, 63, 65, 66, 67, 69, 70, 72, 96, 104, 147 community relations, 96 compatibility, 64, 93, 147 competition, 96 complexity, 89, 139 compliance, 32, 34, 35, 37, 40, 41, 43, 44, 45, 46 complications, 8 composition, viii, 23, 47, 49, 54, 55, 57, 70 compounds, 3, 128 comprehension, viii, 47, 49, 50, 51, 52, 53, 54, 55, 57, 58, 59, 60, 81 compulsory education, 147 computation, 52, 54 computed tomography, 8 computer science, viii, 47, 57, 58, 59, 129 computer self-efficacy, 77 computer simulation, 24 computer skills, 89 computer technology, vii, x, 48, 87, 88, 148 computing, 52, 56

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Index concept map, 120, 122 conceptual model, 52, 58 conceptualization, 55, 111, 114, 139 conference, 98 confirmation bias, 141 conjugation, 7, 14, 20, 21, 23, 24, 135 conscious perception, 37 consciousness, 84 consensus, 30, 89, 102, 104 conservation, 128 construct validity, 109 contamination, 33, 34, 37, 39, 40, 41, 42, 45, 46 control group, 50, 53 control measures, 34 convention, 122 coordination, 69 copolymers, 16 cornea, 10 coronavirus, 39 correlation, 41, 105, 132 cost, 21, 22, 32, 34, 43, 54, 64, 67, 91, 92 cost constraints, 54 cost saving, 34 cost-benefit analysis, 43 cough, 34 covering, 34 creativity, 104, 108, 109 critical infrastructure, ix, 62 critical thinking, vii, xi, 50, 51, 59, 64, 65, 71, 78, 80, 107, 137, 139, 140, 141, 142, 143 criticism, 105 culture, 23, 89, 98, 104, 118, 143 curricula, x, 58, 63, 64, 68, 69, 70, 80, 87, 115, 122 curriculum, 49, 65, 66, 68, 70, 95, 111, 112, 122 curriculum development, 122 cyclooxygenase, 27 Cyprus, 98 cytotoxicity, 23 Czech Republic, 16

D damages, iv data analysis, 108, 114, 119 data collection, 109, 112 data structure, 54 deduction, 50, 78 deficiencies, 48, 49 deficit, 68 degradation, 3, 4, 5, 7, 21, 24, 29 democratization, 147 demographic factors, ix, 75 demonstrations, 112 Denmark, 36

Department of Health and Human Services, 72 Department of Homeland Security, 72, 73 deposition, 10 derivatives, 3, 23, 25, 134 detection, 3 detoxification, 29 developed countries, 32 developmental process, 53 diffusion, 13 digital technologies, 77 diploid, 130 dirt, 38 disaster, viii, ix, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72 discomfort, 115 discourse, 51 discrimination, 32 disinfection, 37, 38, 45 disposition, 139 distance learning, 93 divergence, 22, 111 diversification, 147, 148 diversity, 95, 145, 147 DNA, vii, xi, 2, 5, 7, 8, 14, 17, 23, 24, 125, 127, 128, 129, 130, 131, 134, 135 DNA damage, 134 DNA lesions, 127 DNA polymerase, xi, 125, 127, 129, 130, 131, 134, 135 doctors, 37, 42 dosage, 21 dosing, 21 downsizing, 69 draft, xi, 137 drawing, 48, 52, 83 dream, 79 drug delivery, viii, 2, 5, 9, 14, 15, 18, 19, 28 drug discovery, xi, 125 drug release, 19, 20 drugs, vii, 2, 3, 12, 14, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28, 128 drying, 40, 45 durability, 35 dyes, 20

E ecology, 82 economic status, ix, 75 eczema, 46 edema, vii, 2, 16 educational materials, 41 educational practices, 57 educational process, 76

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Index

educational research, 101, 102, 123 educational services, 145, 146, 148 educational system, 90, 147 EEA, 149 efficiency, 57, 91, 131 egg, 2, 14 egocentrism, 48 elaboration, 140 e-learning, 79, 93 electrodes, 40, 45 electroencephalogram, 45 electron, 16, 134 elementary school, xi, 101, 102, 113, 115, 121 elementary teachers, 113, 114, 115, 116, 122 elucidation, 10 emergency management, ix, 62 emotion, 80 emotional state, 81 employees, 146, 148 employment, 89, 148 encapsulation, 20 encoding, 134 encouragement, 41 endothelium, 27 engineering, 40, 92, 139 enrollment, 64 environmental contamination, 39 environmental protection, 146 enzymes, 127 EPA, xi, 138 epidemic, 11 epidemiologic studies, 40 epidemiology, 39 equipment, 32, 33, 35, 36, 40, 46, 63, 70, 96 ester, 6 eukaryote, 129 Eurasia, 123 European Commission, 139 European Union, 149 evacuation, 66 examinations, 102 exclusion, 82 excretion, 7, 21, 24, 29 execution, 54, 101 executive function, 77 exercise, 65, 67, 69, 70, 71, 88, 95 expertise, 48, 51, 53, 56, 58, 69, 79, 95, 129 experts, viii, 6, 12, 47, 49, 51, 53, 56, 57, 58, 67, 138 exploration, 42, 49 exposure, viii, 13, 31, 32, 33, 34, 35, 36, 40, 43, 44, 50, 79, 113, 130 external environment, 148 extraction, 10

extravasation, 10, 11, 13, 14, 15, 16

F faith, 36 fears, 32 feedback, 40, 41, 66, 79, 140, 141 FEM, 72 FEMA, 65 fidelity, 66, 71 films, 9, 92 filtration, 34 financial resources, 140 Finland, 58 first responders, 65 fish, 3 Fisherman, 118 fission, 132, 135 flexibility, 69, 93 fluid, 3, 10, 13, 16, 26, 27, 34, 41 fluorescence, 3 formamide, 10 foundations, 102, 105 fragments, 4, 53, 131 framing, 103 free radicals, vii, 1, 12, 19, 22, 26 functionalism, 91 funding, 3, 63, 66, 68, 69 fungi, vii, 2, 38

G gambling, 80 gastrointestinal tract, 21 gene expression, 135 general education, 147 general practitioner, 34 genes, 128, 131, 134 genetics, 133 genre, 82 Germany, 4, 11, 18, 110, 137, 143 glasses, 34 glioblastoma, 7 globalization, 88 glucose, 40 glycol, 130 goal-setting, 140 grades, 110 graduate students, 10, 11 grounding, 51 group activities, 66 growth factor, 17 guanine, 13, 126, 127, 134 guidance, ix, 8, 62, 64, 66, 71, 92, 118

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Index guidelines, 35, 40, 43, 44, 69 guiding principles, 145

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H hair, 34 half-life, 7, 12, 20 Hawaii, 123 hazardous materials, 65 hazards, ix, 34, 62, 63, 65, 68, 72 HBV, 31, 32, 39, 41, 46 health education, 40 heat shock protein, 20, 29 heme, 20, 28, 29 heme oxygenase, 20, 28, 29 hepatitis, 32, 39, 41, 45, 46 hepatocellular carcinoma, 9, 18, 21, 25 hepatoma, 8, 9, 15, 21, 25 herpes, 134 herpes virus, 134 high school, 48, 49, 50, 58, 59, 83, 95, 108, 110, 111, 121 higher education, 147 HIV, 31, 32, 37, 39, 40, 41, 42, 44, 46 honesty, 149 Hong Kong, 47, 98 host, vii, 2, 12, 22, 66, 140 house dust, 11, 25 human agency, 82 human immunodeficiency virus, 41, 42 human resources, 145 hybrid, 130 hydrogen, 127, 128 hydrogen bonds, 128 hydrolysis, 4 hygiene, 32, 33, 37, 39, 40, 42, 43, 44, 45, 46 hypermedia, 57, 85 hypertension, 15, 28 hypothesis, 14, 51, 52, 54, 78, 132 hypothesis test, 78 hypoxia, 18 hypoxia-inducible factor, 18

I ideal, 5, 8, 20, 70 image, 25 images, 9, 15, 16, 80, 121 imagination, 72, 78, 104, 118 immersion, 80, 84 immune response, 12 immune system, 128 immunogenicity, 7, 20 immunoglobulin, 14

immunosuppression, 7 impacts, 56 in vivo, 5, 7, 10, 12, 15, 19, 20, 26, 27, 29 incidence, 35, 41 inclusion, 63, 68, 70 India, 19, 20, 42 individual character, 57 individual characteristics, 57 individual differences, 77, 84, 94 individuality, 114 induction, 29 inflammation, vii, 2, 13, 16, 17, 22, 26 inflammatory disease, 128 information technology, 148 inhibition, 7, 20, 24, 29, 128, 129 inhibitor, 10, 16, 20, 21, 27, 28, 29, 128 inoculation, 45 inoculum, 39 insight, 70, 71, 80, 112, 138 institutional change, 148 instructional design, 69 instructional materials, 56 instructional planning, 114 insulin, 4, 40 integration, xi, 93, 137, 141, 147 intelligence, 60, 65 intensive care unit, 43, 45, 46 intentionality, 48 interdependence, 146 interest groups, 90 interface, 85, 121, 141 interferon, 3, 7 internal consistency, 112 internet addiction, 77 interoperability, 63, 64 intervention, 41, 46, 139, 142 intravenously, 12, 15 irradiation, 130 isolation, 23, 37, 40, 42, 45, 129, 131 Italy, 41, 46

J Japan, 1, 2, 3, 4, 5, 6, 8, 12, 13, 15, 16, 19, 22, 26, 125 jaundice, 9, 29 Jordan, 43 jurisdiction, 67, 70

K kidney, 4, 10 kinetics, 16, 127 knowledge acquisition, 106

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L laboratory tests, 32 landscapes, 84 languages, 53 laparotomy, 8 law enforcement, 63 leadership, 30, 94, 96, 97 leakage, 10, 16, 18 learners, viii, ix, 56, 61, 62, 63, 76, 78, 79, 85, 91, 95, 102, 107, 117 learning, viii, x, 47, 48, 49, 50, 51, 52, 53, 55, 56, 57, 59, 60, 61, 64, 66, 67, 71, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 87, 89, 90, 91, 92, 93, 94, 95, 98, 101, 102, 107, 109, 110, 114, 115, 118, 119, 120, 121, 123, 126, 133, 139, 142, 143, 146, 147, 148, 149 learning environment, viii, 60, 61, 71, 78, 79, 107, 120, 142 learning outcomes, 79 learning process, 48, 56, 91, 95 learning styles, 82, 148 learning task, 148 leisure, 78, 80 leisure time, 78, 80 lens, ix, 75, 76 lesions, 13, 14, 126 leucine, 28 leukemia, 4, 5, 7, 20, 29 liberation, 11 librarians, 66 life expectancy, 8 life sciences, 2 ligand, 25 limitations, x, 78, 81, 101, 112 lipids, 5, 13 liposomes, vii, 2, 14, 17 liquid chromatography, 4 literacy, ix, x, 49, 50, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 101, 102, 103, 107, 110, 113, 122, 123, 143 liver, 8, 9, 18, 21, 25 liver cancer, 18, 21, 25 local government, ix, 62 localization, 27, 134 locus, 77, 84 longitudinal study, 83 long-term memory, 55 low risk, 36 loyalty, 149 lung cancer, 30 lymph, 5, 9 lymph node, 5, 9

lymphatic system, 5, 8, 9 lymphoid, 23 lymphoma, 4, 23 lysine, 5, 14

M machinery, 96 macromolecules, vii, 2, 5, 10, 14, 17, 18, 27 macrophages, 7 majority, 35 Malaysia, 34, 43 management, ix, x, 42, 56, 61, 62, 63, 65, 66, 67, 68, 69, 70, 71, 72, 87, 90, 93, 96, 98, 145, 146, 148 mandates, 33 mandatory retirement, 19 manipulation, 67 manpower, 97 manufacturing, 6, 92 mapping, 51, 55 marketing, 6, 21 mass communication, 143 mathematics, 51, 98, 102 mathematics education, 98 matrix, 17, 27, 39 matrix metalloproteinase, 17, 27 mechanical engineering, vii, x, 87 media, ix, 65, 66, 75, 76, 77, 78, 79, 80, 81, 82, 84, 138, 143 melanoma, 16 memory, 53, 54, 56, 85, 119 mental ability, 50 mental model, 48, 51, 77 mental representation, 51, 55, 59, 60, 84 mentor, 2, 16 metabolism, 18 metacognitive skills, 85 metalloproteinase, 10 metastasis, 5 methodology, 50, 57, 63, 68, 82, 97 mice, 12, 14, 15, 20, 24, 25, 26, 28 micelles, vii, 2, 14, 19, 20, 28 microcirculation, 28 microheterogeneity, 2 microscope, 16 microstructures, 55 Ministry of Education, 22 misconceptions, 48 mobile device, xi, 137, 140, 141 mobile phone, 76, 140 modeling, 58, 129 modelling, 50, 53, 77, 82 modification, 2, 5, 14, 20, 55 mold, 89

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

157

Index molecular biology, 127 molecular mass, 6 molecular weight, 25, 27 molecules, 13, 26 monitoring, 40, 41 morale, 90 Moscow, 21, 26 motivation, 45, 80, 94, 126, 133 mucous membrane, viii, 31, 33, 34 mucous membranes, viii, 31, 33, 34 mucus, 39 multidimensional, viii, ix, 61, 62, 63, 64, 103 multimedia, 67, 70, 71 multiple factors, 17 multiplication, 12 music, 56 music therapy, 56 mutagen, 26, 130 mutant, vii, 1, 129, 130, 131, 132, 134, 135 mutation, 13, 22, 26, 131, 135 myocardial infarction, 19

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N nanomedicine, vii, 2, 15 nanoparticles, xi, 17, 138 nanotechnology, 138, 142, 143 National Institute for Occupational Safety and Health, 44 National Institutes of Health, 3 National Research Council, 103, 123 National Response Framework, ix, 62, 64, 71, 72 natural disasters, 71 natural killer cell, 7 natural laws, 108 NCS, vii, 1, 3, 4, 5, 6, 7, 8, 12, 14, 20, 21 negative attitudes, 108 neovascularization, 16 new media, 77, 78, 80, 81 nitric oxide, viii, 2, 13, 26, 27, 29 nitric oxide synthase, 27 nitrogen, vii, 1 NMR, 21 nucleic acid, 13, 26 nurses, 35, 37, 40, 42, 43, 44 nursing, 66, 70 nutrients, 13, 16, 18

O obesity, 140 oil, 13, 26 Oklahoma, 15, 46, 63 one dimension, viii, 61

opportunities, 37, 63, 64, 65, 70, 71, 76, 77, 79, 81, 82, 89, 91, 92, 133, 139, 146, 147 organ, 23 organizational culture, 145 osmotic pressure, 18 ownership, 67, 89, 109 oxidation, 126, 127, 133, 134 oxidative stress, 12, 26 oxygen, 13, 16, 18, 19, 26, 28

P p53, 126 Pacific, 98 pain, vii, 2, 10, 16 pandemic, 39 paradigm, 26, 57, 58, 63, 69, 79, 105 paradigm shift, 63, 69 parallel, 13, 58, 118 parallelism, 48 pathogenesis, vii, 1, 2, 12, 25, 26 pathogens, viii, 12, 31, 32, 33, 37, 38, 41, 45 pathologist, 4 pathophysiology, 18 pathways, 128 patient care, 33, 37, 42, 43, 65 pedagogy, xi, 48, 60, 79, 81, 84, 101, 102, 143 peptides, 23 performance, ix, 22, 33, 40, 49, 50, 56, 62, 71, 111, 120, 146 permeability, vii, 2, 7, 13, 14, 16, 17, 19, 25, 27, 28, 29 permission, iv, 15 peroxynitrite, 13, 26, 27 personal control, 81 personal relations, 92 personal relationship, 92 personality factors, ix, 75 personality traits, 84 pesticide, xi, 138 pharmaceuticals, 6, 20, 128, 129 pharmacokinetics, 5, 7, 16, 20, 21, 23 pharmacology, 6, 7, 29 phenotype, 132 photoirradiation, 134 photooxidation, 134 physical sciences, 88 physical therapy, 70 physics, 57, 112, 122 physiology, 18 pigs, 10, 25 pilot study, 97 planning, ix, 53, 62, 64, 69, 71, 72, 88, 92, 121 plants, x, 87

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

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158

Index

plasma proteins, 10 platform, 79, 93 pleasure, 81 pneumonia, 11, 26 point mutation, xi, 125, 126, 127, 135 political party, 138 politics, 148 polymer, vii, 1, 2, 5, 6, 7, 12, 15, 20, 21, 23, 24, 25, 26, 29 polymerase, 130, 131, 134 polymers, 5, 16, 27 polypeptide, 24, 131 portfolio, 119 positive attitudes, 113 positive feedback, 66, 67 positive relationship, 113 power relations, 90 preparedness, viii, 61, 63, 65, 71, 72 presentation skills, 94 prestige, 147 prevention, ix, 32, 35, 40, 41, 43, 45, 62 primacy, 82 primary school, 90 prior knowledge, 14 problem solving, 48, 58, 59, 60, 78, 107, 111, 122 problem-based learning, 79, 92 problem-solving, 49, 50, 51, 58, 65, 71 problem-solving skills, 49, 50, 65 problem-solving strategies, 51 procedural knowledge, 53 productivity, 103 programming, viii, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 programming languages, 52 project, 3, 4, 6, 11, 45, 94, 95, 139 proliferation, 135 propagation, 13 prophylaxis, 32 protease inhibitors, 2, 14 proteases, vii, 1, 2, 10, 11, 12, 19, 25 proteins, 2, 7, 10, 12, 13, 14, 20, 21, 24, 26, 128 proteolytic enzyme, 24 proteomics, 128 prototype, 21, 24, 28, 29 Pseudomonas aeruginosa, 10 psychology, x, 75, 76, 81 psychosocial factors, 77 public health, 63, 70, 72 public support, 109 purines, 13 purity, 3

Q qualifications, 89, 90 qualitative research, 112 quality assurance, 145, 148 quality improvement, ix, 62 quality standards, xi, 89, 145 quantum chemistry, 127 quartile, 51 questioning, 105, 115 quizzes, 66

R radiation, 127, 134 radicals, 12, 26 radio, 10, 93 radiologists, 14 reactions, 22, 91, 127 reactive oxygen, vii, 1, 21 reactivity, 127, 128 reading, 77, 78, 80, 82, 84, 122 reading comprehension, 122 real time, 67, 71 realism, 69 reality, 64, 89, 117 reasoning, 50, 78, 85 reasoning skills, 78 recall, 51, 80 recall information, 80 recognition, 12, 32, 51, 63, 81, 146 recommendations, iv, viii, 11, 32, 45, 47, 57 recurrence, 8 referees, 14 reflection, 78, 94, 115, 119, 120 regression, 91 reinforcement, 77, 85 relatives, 5 relevance, ix, 62, 81, 95 reliability, 112, 116 relief, 14 religion, 118, 121 renal cell carcinoma, 18 replication, 39, 127, 129, 134 reproduction, 11 requirements, 82, 91, 97, 139, 147, 148 research and development, 97 residues, 3, 6 resilience, 72 resistance, 29 resolution, 30, 66 resources, 3, 67, 72, 76, 79, 80, 95, 103, 145, 148 respect, 35, 77, 79, 113, 120, 132, 138, 141

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,

159

Index respirator, 34 respiratory failure, 43 retirement, 12, 19, 25 risk factors, 43 risk perception, 42 robotics, 96 room temperature, 40, 45 rotations, 69 Royal Society, 103

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S saliva, 34 salmonella, 28 satellite technology, 67 schema, 53, 55, 56, 113 school activities, 148 science education, vii, x, xi, 57, 101, 103, 107, 116, 121, 122, 123, 137, 142, 143 scientific knowledge, x, 101, 102, 103, 104, 105, 106, 107, 108, 109, 111, 113, 117, 118, 119, 120 scientific method, 114 scientific observation, 104 scientific theory, 114 scientific understanding, 106, 109 screening, 3, 22 secondary education, 97 secondary schools, 123 secrete, 27 selectivity, vii, 2 self esteem, 84 self-assessment, 90, 94 self-concept, 83 self-control, 84 self-efficacy, 77 self-esteem, 77, 80, 83 self-image, 84 self-regulation, 140 self-reports, 83 semantics, 48, 53 seminars, 80 senescence, 132, 135 senses, 119 sensitivity, 3, 130, 131 sequencing, 3, 4 serine, 11 serology, 32 severe acute respiratory syndrome, 39 sexual reproduction, 132 shape, 81 shock, 29 short-term memory, 54 side effects, 21 signaling pathway, 13, 128

simulation, 24, 90 skill acquisition, 78 skills base, 79, 80 skills training, 97 skin, viii, 10, 15, 31, 33, 34, 38 smooth muscle, 18 social change, 147 social context, 76, 104 social environment, 91, 94 social influence, 84 social influences, 84 social integration, 147 social policy, 143 social problems, 147 social responsibility, 146 social software, 84 sodium, 39 solid tumors, vii, 2, 10, 14, 15, 17, 18, 22, 25, 26 Southeast Asia, 43 space, 5, 10, 18, 90 special education, 147 specialization, 68, 147 species, vii, 1, 21, 43, 133 specifications, 5, 54 speculation, 89 sperm, xi, 138 spleen, 10 stakeholders, 66, 146 standardization, 63 sterile, 33 storage, 53 strategy, 5, 7, 26, 47, 51, 53, 55, 58, 68, 72 streams, 69 structuralism, 91 styrene, vii, 1, 5, 6, 7, 23, 24, 28 subcutaneous injection, 5 successive approximations, 64, 66 supervision, 3 supervisors, 133 support services, 4 surgical resection, 8 survey, 41, 44, 60, 68 survival, 12, 20, 40, 129 synthesis, 4, 6, 7, 24, 91, 130, 134

T T cell, 7 tactics, ix, 61 Taiwan, 80, 83 taxonomy, 133 teacher preparation, 113, 115 teacher training, 98, 107, 116 teaching experience, 111

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Index

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160

teaching materials, 93, 94 technical change, 147 technological developments, 97 temperature, 38, 129, 130, 131, 134, 135 terrorism, 63, 65, 71 testing, 48, 50 textbooks, 48, 125 therapeutics, 6, 15, 26, 27, 28 therapy, 7, 8, 28, 29 thermostability, 130, 131 think critically, 139, 142 thoughts, 101 threats, ix, 62 time management, 94 tissue, 5, 8, 9, 10, 13, 14, 15, 16, 18, 19, 21, 24, 27 toxicity, 20, 28, 29 traditional views, 116, 117, 118 traditions, 147 trainees, 98 training, ix, x, 36, 40, 41, 62, 63, 64, 72, 73, 87, 89, 90, 97, 98, 147, 149 training programs, 147 trajectory, 115 transcription, 128 transfection, 131 transference, 93 transferrin, 14 translation, 111, 114, 115 translocation, 130, 131 transmission, viii, 31, 32, 33, 37, 39, 40, 41, 42, 43, 44, 45 transversion mutation, 134 trauma, 43, 44 trial, 116, 127 triggers, 12 troubleshooting, 148 trypsin, 4, 16 tuberculosis, 33 tumor cells, 18, 20, 22, 29 tumor growth, 13, 16, 18 tumor necrosis factor, 17 tumors, vii, viii, 2, 7, 8, 14, 15, 16, 17, 18, 19, 22, 27, 28 tumour growth, 29 tumours, 29 Turkey, 34, 87, 102, 145 typology, 77 tyrosine, 13

United Kingdom, 103 universality, 119 universities, 48, 126 university education, 126, 133 urea, 4 urinary bladder, 7 urine, 14, 37, 38 US Department of Health and Human Services, 72

V validation, 120 vancomycin, 43, 46 vasculature, 16, 18, 28 vehicles, 66 velocity, 21 venue, 66, 70 vessels, 16, 18 victims, 67 video, 83, 84 video games, 83 Vietnam, 4 violence, 4 viral diseases, 26 viral infection, vii, 1, 12, 32 virus infection, vii, 1, 12, 13, 26 viruses, 38, 39, 41, 45, 46, 63, 128 vision, ix, 62, 148 vocabulary, 78 vocational education, 89, 96, 98, 147 vulnerability, 63 Vygotsky, 79

W waste, 35, 45 wealth, 81 word processing, 76 workers, viii, x, 31, 32, 33, 35, 36, 37, 40, 41, 42, 43, 44, 45, 46, 87 working groups, 89 working memory, 53, 54, 77, 80 workplace, viii, 31, 40, 121 World Trade Center, 63

X X chromosome, 134 X-ray, 8, 9, 21, 25

Z

U underlying mechanisms, 109 unhappiness, 90

zinc, 20, 28, 29

Science Education in a Rapidly Changing World, edited by Seth D. Grahame, Nova Science Publishers, Incorporated, 2011. ProQuest Ebook Central,