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1.  Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971 
Human Reproduction (Oxford, England)  2010;25(9):2157-2174.
In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical ‘Studies on Human Reproduction’. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology.
The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision.
We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants’ high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support.
This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research.
PMCID: PMC2922998  PMID: 20657027
Robert Edwards; funding; history; human conception; IVF; Medical Research Council; Patrick Steptoe
2.  Cost-Effectiveness of Interventions to Promote Physical Activity: A Modelling Study 
PLoS Medicine  2009;6(7):e1000110.
Linda Cobiac and colleagues model the costs and health outcomes associated with interventions to improve physical activity in the population, and identify specific interventions that are likely to be cost-saving.
Physical inactivity is a key risk factor for chronic disease, but a growing number of people are not achieving the recommended levels of physical activity necessary for good health. Australians are no exception; despite Australia's image as a sporting nation, with success at the elite level, the majority of Australians do not get enough physical activity. There are many options for intervention, from individually tailored advice, such as counselling from a general practitioner, to population-wide approaches, such as mass media campaigns, but the most cost-effective mix of interventions is unknown. In this study we evaluate the cost-effectiveness of interventions to promote physical activity.
Methods and Findings
From evidence of intervention efficacy in the physical activity literature and evaluation of the health sector costs of intervention and disease treatment, we model the cost impacts and health outcomes of six physical activity interventions, over the lifetime of the Australian population. We then determine cost-effectiveness of each intervention against current practice for physical activity intervention in Australia and derive the optimal pathway for implementation. Based on current evidence of intervention effectiveness, the intervention programs that encourage use of pedometers (Dominant) and mass media-based community campaigns (Dominant) are the most cost-effective strategies to implement and are very likely to be cost-saving. The internet-based intervention program (AUS$3,000/DALY), the GP physical activity prescription program (AUS$12,000/DALY), and the program to encourage more active transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high probability of being under a AUS$50,000 per DALY threshold. GP referral to an exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if high time and travel costs for patients in screening and consulting an exercise physiologist are considered.
Intervention to promote physical activity is recommended as a public health measure. Despite substantial variability in the quantity and quality of evidence on intervention effectiveness, and uncertainty about the long-term sustainability of behavioural changes, it is highly likely that as a package, all six interventions could lead to substantial improvement in population health at a cost saving to the health sector.
Please see later in the article for Editors' Summary
Editors' Summary
The human body needs regular physical activity throughout life to stay healthy. Physical activity—any bodily movement produced by skeletal muscles that uses energy—helps to maintain a healthy body weight and to prevent or delay heart disease, stroke, type 2 diabetes, colon cancer, and breast cancer. In addition, physically active people feel better and live longer than physically inactive people. For an adult, 30 minutes of moderate physical activity—walking briskly, gardening, swimming, or cycling—at least five times a week is sufficient to promote and maintain health. But at least 60% of the world's population does not do even this modest amount of physical activity. The daily lives of people in both developed and developing countries are becoming increasingly sedentary. People are sitting at desks all day instead of doing manual labor; they are driving to work in cars instead of walking or cycling; and they are participating less in physical activities during their leisure time.
Why Was This Study Done?
In many countries, the chronic diseases that are associated with physical inactivity are now a major public-health problem; globally, physical inactivity causes 1.9 million deaths per year. Clearly, something has to be done about this situation. Luckily, there is no shortage of interventions designed to promote physical activity, ranging from individual counseling from general practitioners to mass-media campaigns. But which intervention or package of interventions will produce the optimal population health benefits relative to cost? Although some studies have examined the cost-effectiveness of individual interventions, different settings for analysis and use of different methods and assumptions make it difficult to compare results and identify which intervention approaches should be give priority by policy makers. Furthermore, little is known about the cost-effectiveness of packages of interventions. In this study, the researchers investigate the cost-effectiveness in Australia (where physical inactivity contributes to 10% of deaths) of a package of interventions designed to promote physical activity in adults using a standardized approach (ACE-Prevention) to the assessment of the cost-effectiveness of health-care interventions.
What Did the Researchers Do and Find?
The researchers selected six interventions for their study: general practitioner “prescription” of physical activity; general practitioner referral to an exercise physiologist; a mass-media campaign to promote physical activity; the TravelSmart car use reduction program; a campaign to encourage the use of pedometers to increase physical activity; and an internet-based program. Using published data on the effects of physical activity on the amount of illness and death caused by breast and colon cancer, heart disease, stroke, and type 2 diabetes and on the effectiveness of each intervention, the researchers calculated the health outcomes of each intervention in disability-adjusted life years (DALY; a year of healthy life lost because of premature death or disability) averted over the lifetime of the Australian population. They also calculated the costs associated with each intervention offset by the costs associated with the five conditions listed above. These analyses showed that the pedometer program and the mass-media campaign were likely to be the most cost-effective interventions. These interventions were also most likely to be cost-saving. Referral to an exercise physiologist was the least cost-effective intervention. The other three interventions, though unlikely to be cost-saving, were likely to be cost-effective. Finally, a package of all six interventions would be cost-effective and would avert 61,000 DALYs, a third of what could be achieved if every Australian did 30 minutes of physical activity five times a week.
What Do These Findings Mean?
As in all modeling studies, these findings depend on the quality of the data and on the assumptions included by the researchers in their calculations. Unfortunately, there was substantial variability in the quantity and quality of evidence on the effectiveness of each intervention and uncertainty about the long-term effects of each intervention. Nevertheless, the findings presented in this study suggest that the assessment of the cost-effectiveness of a combination of interventions designed to promote physical activity might provide policy makers with some guidance about the best way to reduce the burden of disease caused by physical inactivity. More specifically, for Australia, these findings suggest that the package of the six interventions considered here is likely to provide a cost-effective way to substantially improve the health of the nation.
Additional Information
Please access these Web sites via the online version of this summary at
The World Health Organization provides information about physical activity and health (in several languages); it also provides an explanation of DALYs
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups and for health professionals
The UK National Health Service information source Choices also explains the benefits of regular physical activity
MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish)
The University of Queensland Web site has more information on ACE-Prevention (Assessing Cost-Effectiveness Prevention)
PMCID: PMC2700960  PMID: 19597537
3.  Attitudes of medical students to HIV and AIDS. 
Genitourinary Medicine  1993;69(5):377-380.
OBJECTIVE--To assess the knowledge and attitudes of medical students to HIV/AIDS and whether attitudes correlate with knowledge and clinical experience. To determine if students felt adequately prepared to deal with medical and psychological aspects of HIV/AIDS. SUBJECTS AND METHODS--The subjects consisted of 190 London and 99 Cambridge medical students at the end of their genitourinary medicine attachment, plus 230 Cambridge medical students at the end of their second pre-clinical year. Between March 1991 and February 1992 all were asked to complete an anonymous questionnaire, covering factual knowledge and attitudes towards HIV/AIDS. MAIN RESULTS--Cambridge genitourinary medicine students, despite spending less time studying HIV infection than their London counterparts gave more correct answers to the factual questions, although this difference did not reach significance (52.4% vs. 47.5%, p = 0.14). One third of students believed that many health care workers were at high risk of acquiring HIV at work and one fifth thought doctors should have the right to refuse to treat people with HIV. Fourteen percent of Cambridge genitourinary medicine students indicated that most British people with HIV have only themselves to blame, by comparison with 4% of London students (p = 0.003). Thirty-nine per cent of Cambridge genitourinary medicine students expressed reluctance to care for someone with AIDS by comparison with 10% of London students (p = 0.0001). CONCLUSIONS--It is important that medical educators convey accurate information about HIV, including the actual risks posed by occupational exposure and try to ensure that medical students spend sufficient time seeing patients with HIV/AIDS during their training.
PMCID: PMC1195122  PMID: 8244357
4.  Emerging Use of Gene Expression Microarrays in Plant Physiology 
Microarrays have become an important technology for the global analysis of gene expression in humans, animals, plants, and microbes. Implemented in the context of a well-designed experiment, cDNA and oligonucleotide arrays can provide highthroughput, simultaneous analysis of transcript abundance for hundreds, if not thousands, of genes. However, despite widespread acceptance, the use of microarrays as a tool to better understand processes of interest to the plant physiologist is still being explored. To help illustrate current uses of microarrays in the plant sciences, several case studies that we believe demonstrate the emerging application of gene expression arrays in plant physiology were selected from among the many posters and presentations at the 2003 Plant and Animal Genome XI Conference. Based on this survey, microarrays are being used to assess gene expression in plants exposed to the experimental manipulation of air temperature, soil water content and aluminium concentration in the root zone. Analysis often includes characterizing transcript profiles for multiple post-treatment sampling periods and categorizing genes with common patterns of response using hierarchical clustering techniques. In addition, microarrays are also providing insights into developmental changes in gene expression associated with fibre and root elongation in cotton and maize, respectively. Technical and analytical limitations of microarrays are discussed and projects attempting to advance areas of microarray design and data analysis are highlighted. Finally, although much work remains, we conclude that microarrays are a valuable tool for the plant physiologist interested in the characterization and identification of individual genes and gene families with potential application in the fields of agriculture, horticulture and forestry.
PMCID: PMC2447420  PMID: 18629133
5.  Healthy travel and the socio-economic structure of car commuting in Cambridge, UK: A mixed-methods analysis 
Social Science & Medicine (1982)  2012;74(12):1929-1938.
Car use is associated with substantial health and environmental costs but research in deprived populations indicates that car access may also promote psychosocial well-being within car-oriented environments. This mixed-method (quantitative and qualitative) study examined this issue in a more affluent setting, investigating the socio-economic structure of car commuting in Cambridge, UK. Our analyses involved integrating self-reported questionnaire data from 1142 participants in the Commuting and Health in Cambridge study (collected in 2009) and in-depth interviews with 50 participants (collected 2009–2010). Even in Britain's leading ‘cycling city’, cars were a key resource in bridging the gap between individuals' desires and their circumstances. This applied both to long-term life goals such as home ownership and to shorter-term challenges such as illness. Yet car commuting was also subject to constraints, with rush hour traffic pushing drivers to start work earlier and with restrictions on, or charges for, workplace parking pushing drivers towards multimodal journeys (e.g. driving to a ‘park-and-ride’ site then walking). These patterns of car commuting were socio-economically structured in several ways. First, the gradient of housing costs made living near Cambridge more expensive, affecting who could ‘afford’ to cycle and perhaps making cycling the more salient local marker of Bourdieu's class distinction. Nevertheless, cars were generally affordable in this relatively affluent, highly-educated population, reducing the barrier which distance posed to labour-force participation. Finally, having the option of starting work early required flexible hours, a form of job control which in Britain is more common among higher occupational classes. Following a social model of disability, we conclude that socio-economic advantage can make car-oriented environments less disabling via both greater affluence and greater job control, and in ways manifested across the full socio-economic range. This suggests the importance of combining individual-level ‘healthy travel’ interventions with measures aimed at creating travel environments in which all social groups can pursue healthy and satisfying lives.
► This mixed-method study illustrates how cars simultaneously enable and constrain well-being in everyday life. ► Car commuting helped workers in Cambridge (UK) meet life goals (e.g. home ownership) and overcome challenges (e.g. illness). ► Relying on cars also introduced constraints, however, and triggered ‘counter-adaptations’ such as starting work earlier. ► Socio-economic advantage made it easier to achieve sustaining daily routines, via greater affluence and greater job control. ► Thus socio-economic advantage can make car-oriented environments less ‘disabling’, even in a relatively affluent population.
PMCID: PMC3611603  PMID: 22465380
Cars; Travel behaviour; Commuting; Socio-economic factors; Mixed-method; UK
6.  The Improved Physical Activity Index for Measuring Physical Activity in EPIC Germany 
PLoS ONE  2014;9(3):e92005.
In the European Investigation into Cancer and Nutrition study (EPIC), physical activity (PA) has been indexed as a cross-tabulation between PA at work and recreational activity. As the proportion of non-working participants increases, other categorization strategies are needed. Therefore, our aim was to develop a valid PA index for this population, which will also be able to express PA continuously. In the German EPIC centers Potsdam and Heidelberg, a clustered sample of 3,766 participants was re-invited to the study center. 1,615 participants agreed to participate and 1,344 participants were finally included in this study. PA was measured by questionnaires on defined activities and a 7-day combined heart rate and acceleration sensor. In a training sample of 433 participants, the Improved Physical Activity Index (IPAI) was developed. Its performance was evaluated in a validation sample of 911 participants and compared with the Cambridge Index and the Total PA Index. The IPAI consists of items covering five areas including PA at work, sport, cycling, television viewing, and computer use. The correlations of the IPAI with accelerometer counts in the training and validation sample ranged r = 0.40–0.43 and with physical activity energy expenditure (PAEE) r = 0.33–0.40 and were higher than for the Cambridge Index and the Total PA Index previously applied in EPIC. In non-working participants the IPAI showed higher correlations than the Cambridge Index and the Total PA Index, with r = 0.34 for accelerometer counts and r = 0.29 for PAEE. In conclusion, we developed a valid physical activity index which is able to express PA continuously as well as to categorize participants according to their PA level. In populations with increasing rates of non-working people the performance of the IPAI is better than the established indices used in EPIC.
PMCID: PMC3958414  PMID: 24642812
7.  Mild Traumatic Brain Injury and Executive Functions in School-Aged Children 
Developmental neurorehabilitation  2009;12(5):330-341.
This study sought to examine the effects of mild traumatic brain injury (TBI) on executive functions in school-aged children.
Participants and Method
The prospective, longitudinal study involved 8–15 year old children, 186 with mild TBI and 99 with mild orthopedic injuries (OI). They were administered the Stockings of Cambridge and Spatial Working Memory subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) about 10 days, 3 months, and 12 months post-injury. Parents completed the Behavior Rating Inventory of Executive Functions (BRIEF) on each occasion, with ratings at the initial assessment intended to assess premorbid functioning retrospectively.
On the CANTAB, the groups did not differ on the Stockings of Cambridge, and the mild TBI group unexpectedly performed better than the OI group on Spatial Working Memory. On the BRIEF, children with mild TBI showed a marginally significant trend toward more problems than the OI group on the Metacognition Index composite. The only BRIEF subscale on which they demonstrated significantly more problems was Organization of Materials. The presence of intracranial abnormalities on MRI was associated with more problems on the BRIEF Organization of Materials subscale at 3 months, but other findings were not consistent with hypothesized effects of TBI severity. The CANTAB subtests were significant predictors of later ratings on the BRIEF, but accounted for modest variance.
Children with mild TBI show limited evidence of deficits in executive functions, either cognitively or behaviorally, irrespective of injury characteristics. Cognitive tests of executive functions are modest predictors of ratings of executive functions in everyday life, for children both with and without mild TBI.
PMCID: PMC3013371  PMID: 20477562
8.  A veterinary President 
On 21 July, Lord Soulsby of Swaffham Prior took office as President of the Royal Society of Medicine. He qualified mrcvs from Edinburgh in 1948 and held lectureships in Bristol and Cambridge before appointment as Professor of Parasitology in the University of Pennsylvania in 1964. There he stayed for fourteen years, returning to Cambridge in 1978 as Professor of Animal Pathology (now Emeritus). His work as a parasitologist has taken him to the USSR, Nigeria, India, Australia, South America, China and numerous countries of Europe. Earlier presidencies have included the Royal College of Veterinary Surgeons, the World Association for the Advancement of Parasitology, the Cambridge Society for Comparative Medicine, and the Comparative Medicine Section of the RSM (1993–95); he is Patron of the Fund for Replacement of Animals in Medical Experiments. He has been a consultant to international bodies including WHO, the UN Development Programme, FAO, and the International Atomic Energy Agency. Created a life peer in 1990 (now on the Opposition benches), he chaired a Select Committee on antibiotic resistance whose report appeared earlier this year. He is interviewed here by Robin Fox.
PMCID: PMC1296884  PMID: 9849527
9.  Adventures in public data 
This article contains the slides and transcript of a talk given by Dan Zaharevitz at the "Visions of a Semantic Molecular Future" symposium held at the University of Cambridge Department of Chemistry on 2011-01-19. A recording of the talk is available on the University Computing Service's Streaming Media Service archive at (unfortunately the first part of the recording was corrupted, so the talk appears to begin at slide 6, 'At a critical time'). We believe that Dan's message comes over extremely well in the textual transcript and that it would be poorer for serious editing. In addition we have added some explanations and references of some of the concepts in the slides and text. (Charlotte Bolton; Peter Murray-Rust, University of Cambridge)
Editorial preface
The following paper is part of a series of publications which arose from a Symposium held at the Unilever Centre for Molecular Informatics at the University of Cambridge to celebrate the lifetime achievements of Peter Murray-Rust. One of the motives of Peter's work was and is a better transport and preservation of data and information in scientific publications. In both respects the following publication is relevant: it is about public data and their representation, and the publication represents a non-standard experiment of transporting the content of the scientific presentation. As you will see, it consists of the original slides used by Dan Zaharevitz in his talk "Adventures in Public Data" at the Unilever Centre together with a diligent transcript of his speech. The transcribers have gone through great effort to preserve the original spirit of the talk by preserving colloquial language as it is used at such occasions. For reasons known to us, the original speaker was unable to submit the manuscript in a more conventional form. We, the Editors, have discussed in depth whether such a format is suitable for a scientific journal. We have eventually decided to publish this "as is". We did this mostly because it was Peter's wish that this talk was published in this form and because we agreed with his notion that this format transmits the message just as well as a formal article as defined by our instructions for authors. We, the Editors, wish to make clear however that this is an exception that we made because we would like to preserve the temporal unity and message of this set of publications. Insisting on a formal publication would have meant losing this historical account as part of the thematic series of papers or disrupting the series. We hope that this will find the consent of our readership.
PMCID: PMC3198951  PMID: 22017861
10.  Shift and Day Work: A Comparison of Sickness Absence, Lateness, and other Absence Behaviour at an Oil Refinery from 1962 to 1965 
Despite the increasing use of continuous process shift work in modern industry, few studies on the medical aspects of shift work can be found in recent literature of occupational health. Physiologists have shown that the ability of the body to adjust its circadian rhythms to alteration in hours of work or sleep can take up to a month. The usual type of shift work in industry involves weekly changes of hours, and thus on theoretical grounds at least this may not be the most suitable frequency for shift changes.
Sickness absence of male refinery workers has been studied over a four-year period. The figures show that continuous three-cycle shift workers have consistently and significantly lower rates of sickness than day workers in similar occupations. The annual inception rate (spells) standardized for age was 108% for shift workers and 182% for day workers, and the average annual duration per man was 11 days for shift workers and 18 days for day workers, although the average length of spell was slightly longer among shift workers. As far as is known, such a difference has not been described before in detail.
Age-related lateness and absenteeism have been measured and show similar wide differences between the two groups.
Although both types of worker are largely self-selected, the difference is not due to medical selection or to an excess of any one type of disease in day workers. Over three-quarters of 150 shift workers interviewed stated that they preferred shift work hours and that sleeping difficulties were not common.
It is suggested that the main reasons for the difference between shift and day workers' sickness absence lie in the degree of personal involvement in the work and in the social structure of the working group.
PMCID: PMC1008539  PMID: 6023084
11.  The impact of an exercise physiologist coordinated resistance exercise program on the physical function of people receiving hemodialysis: a stepped wedge randomised control study 
BMC Nephrology  2013;14:204.
Exercise during hemodialysis treatments improves physical function, markers of cardiovascular disease and quality of life. However, exercise programs are not a part of standard therapy in the vast majority of hemodialysis clinics internationally. Hemodialysis unit-based accredited exercise physiologists may contribute to an increased intradialytic exercise uptake and improved physical function.
Methods and design
This is a stepped wedge cluster randomised controlled trial design. A total of 180 participants will be recruited from 15 community satellite hemodialysis clinics in a large metropolitan Australian city. Each clinic will represent a cluster unit. The stepped wedge design will consist of three groups each containing five randomly allocated cluster units, allocated to either 12, 24 or 36 weeks of the intervention. The intervention will consist of an accredited exercise physiologist-coordinated program consisting of six lower body resistance exercises using resistance elastic bands and tubing. The resistance exercises will include leg abduction, plantar flexion, dorsi flexion, straight-leg/bent-knee raise, knee extension and knee flexion. The resistance training will incorporate the principle of progressive overload and completed in a seated position during the first hour of hemodialysis treatment. The primary outcome measure is objective physical function measured by the 30-second sit to stand test. Secondary outcome measures include the 8-foot timed-up-and-go test, the four square step test, quality of life, cost-utility analysis, uptake and involvement in community activity, self-reported falls, fall’s confidence, medication use, blood pressure and morbidity (hospital admissions).
The results of this study are expected to determine the efficacy of an accredited exercise physiologist supervised resistance training on the physical function of people receiving hemodialysis and the cost-utility of exercise physiologists in hemodialysis centres. This may contribute to intradialytic exercise as standard therapy using an exercise physiologist workforce model.
Trial registration
Current Controlled Trials ACTRN12612001223820.
PMCID: PMC3850647  PMID: 24070232
Exercise; Resistance training; Hemodialysis; Dialysis; Stepped wedge; Cluster randomised control trial; Cost utility analysis; Exercise physiologist
12.  Correlates of time spent walking and cycling to and from work: baseline results from the commuting and health in Cambridge study 
Environmental perceptions and psychological measures appear to be associated with walking and cycling behaviour; however, their influence is still unclear. We assessed these associations using baseline data from a quasi-experimental cohort study of the effects of major transport infrastructural developments in Cambridge, UK.
Postal surveys were sent to adults who travel to work in Cambridge (n = 1582). Questions asked about travel modes and time spent travelling to and from work in the last week, perceptions of the route, psychological measures regarding car use and socio-demographic characteristics. Participants were classified into one of two categories according to time spent walking for commuting ('no walking' or 'some walking') and one of three categories for cycling ('no cycling', '1-149 min/wk' and ' ≥ 150 min/wk').
Of the 1164 respondents (68% female, mean (SD) age: 42.3 (11.4) years) 30% reported any walking and 53% reported any cycling to or from work. In multiple regression models, short distance to work and not having access to a car showed strong positive associations with both walking and cycling. Furthermore, those who reported that it was pleasant to walk were more likely to walk to or from work (OR = 4.18, 95% CI 3.02 to 5.78) and those who reported that it was convenient to cycle on the route between home and work were more likely to do so (1-149 min/wk: OR = 4.60, 95% CI 2.88 to 7.34; ≥ 150 min/wk: OR = 3.14, 95% CI 2.11 to 4.66). Positive attitudes in favour of car use were positively associated with time spent walking to or from work but negatively associated with cycling to or from work. Strong perceived behavioural control for car use was negatively associated with walking.
In this relatively affluent sample of commuters, a range of individual and household characteristics, perceptions of the route environment and psychological measures relating to car use were associated with walking or cycling to and from work. Taken together, these findings suggest that social and physical contexts of travel decision-making should be considered and that a range of influences may require to be addressed to bring about behaviour change.
PMCID: PMC3254135  PMID: 22074293
transport; active commuting; environmental perceptions; distance; Theory of Planned Behaviour
13.  Use of the bootstrap method to develop a physical fitness test for public safety officers who serve as both police officers and firefighters 
Physical fitness testing is a common tool for motivating employees with strenuous occupations to reach and maintain a minimum level of fitness. Nevertheless, the use of such tests can be hampered by several factors, including required compliance with US antidiscrimination laws. The Highland Park (Texas) Department of Public Safety implemented testing in 1991, but no single test adequately evaluated its sworn employees, who are cross-trained and serve as police officers and firefighters. In 2010, the department's fitness experts worked with exercise physiologists from Baylor Heart and Vascular Hospital to develop and evaluate a single test that would be equitable regardless of race/ethnicity, disability, sex, or age >50 years. The new test comprised a series of exercises to assess overall fitness, followed by two sequences of job-specific tasks related to firefighting and police work, respectively. The study group of 50 public safety officers took the test; raw data (e.g., the number of repetitions performed or the time required to complete a task) were collected during three quarterly testing sessions. The statistical bootstrap method was then used to determine the levels of performance that would correlate with 0, 1, 2, or 3 points for each task. A sensitivity analysis was done to determine the overall minimum passing score of 17 points. The new physical fitness test and scoring system have been incorporated into the department's policies and procedures as part of the town's overall employee fitness program.
PMCID: PMC4059562  PMID: 24982558
14.  The exoskeletons are here 
It is a fantastic time for the field of robotic exoskeletons. Recent advances in actuators, sensors, materials, batteries, and computer processors have given new hope to creating the exoskeletons of yesteryear's science fiction. While the most common goal of an exoskeleton is to provide superhuman strength or endurance, scientists and engineers around the world are building exoskeletons with a wide range of diverse purposes. Exoskeletons can help patients with neurological disabilities improve their motor performance by providing task specific practice. Exoskeletons can help physiologists better understand how the human body works by providing a novel experimental perturbation. Exoskeletons can even help power mobile phones, music players, and other portable electronic devices by siphoning mechanical work performed during human locomotion. This special thematic series on robotic lower limb exoskeletons and orthoses includes eight papers presenting novel contributions to the field. The collective message of the papers is that robotic exoskeletons will contribute in many ways to the future benefit of humankind, and that future is not that distant.
PMCID: PMC2698881  PMID: 19508711
Technological advances in robotic hardware and software have enabled powered exoskeletons to move from science fiction to the real world. The objective of this article is to emphasize two main points for future research. First, the design of future devices could be improved by exploiting biomechanical principles of animal locomotion. Two goals in exoskeleton research could particularly benefit from additional physiological perspective: 1) reduction in the metabolic energy expenditure of the user while wearing the device, and 2) minimization of the power requirements for actuating the exoskeleton. Second, a reciprocal potential exists for robotic exoskeletons to advance our understanding of human locomotor physiology. Experimental data from humans walking and running with robotic exoskeletons could provide important insight into the metabolic cost of locomotion that is impossible to gain with other methods. Given the mutual benefits of collaboration, it is imperative that engineers and physiologists work together in future studies on robotic exoskeletons for human locomotion.
PMCID: PMC2185037  PMID: 18185840
biomechanics; walking; running; neural control; metabolic cost
16.  Cochlear Implants:System Design, Integration and Evaluation 
As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120,000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues from design and specifications to integration and evaluation. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants.
PMCID: PMC2782849  PMID: 19946565
Auditory prosthesis; electric stimulation; auditory nerve; auditory brainstem; signal processing; radio frequency; current source; hermetic sealing; electrode; loudness; pitch; temporal resolution; fine structure; speech recognition; music perception; biocompatibility; biomaterials; safety
17.  Evaluation of chloroform/methanol extraction to facilitate the study of membrane proteins of non-model plants 
Planta  2010;231(5):1113-1125.
Membrane proteins are of great interest to plant physiologists because of their important function in many physiological processes. However, their study is hampered by their low abundance and poor solubility in aqueous buffers. Proteomics studies of non-model plants are generally restricted to gel-based methods. Unfortunately, all gel-based techniques for membrane proteomics lack resolving power. Therefore, a very stringent enrichment method is needed before protein separation. In this study, protein extraction in a mixture of chloroform and methanol in combination with gel electrophoresis is evaluated as a method to study membrane proteins in non-model plants. Benefits as well as disadvantages of the method are discussed. To demonstrate the pitfalls of working with non-model plants and to give a proof of principle, the method was first applied to whole leaves of the model plant Arabidopsis. Subsequently, a comparison with proteins extracted from leaves of the non-model plant, banana, was made. To estimate the tissue and organelle specificity of the method, it was also applied on banana meristems. Abundant membrane or lipid-associated proteins could be identified in both tissues, with the leaf extract yielding a higher number of membrane proteins.
Electronic supplementary material
The online version of this article (doi:10.1007/s00425-010-1121-1) contains supplementary material, which is available to authorized users.
PMCID: PMC2840667  PMID: 20177697
Chloroform/methanol extraction; Leaf; Meristem; Non-model; Plant membrane proteomics
18.  RoBuST: an integrated genomics resource for the root and bulb crop families Apiaceae and Alliaceae 
BMC Plant Biology  2010;10:161.
Root and bulb vegetables (RBV) include carrots, celeriac (root celery), parsnips (Apiaceae), onions, garlic, and leek (Alliaceae)—food crops grown globally and consumed worldwide. Few data analysis platforms are currently available where data collection, annotation and integration initiatives are focused on RBV plant groups. Scientists working on RBV include breeders, geneticists, taxonomists, plant pathologists, and plant physiologists who use genomic data for a wide range of activities including the development of molecular genetic maps, delineation of taxonomic relationships, and investigation of molecular aspects of gene expression in biochemical pathways and disease responses. With genomic data coming from such diverse areas of plant science, availability of a community resource focused on these RBV data types would be of great interest to this scientific community.
The RoBuST database has been developed to initiate a platform for collecting and organizing genomic information useful for RBV researchers. The current release of RoBuST contains genomics data for 294 Alliaceae and 816 Apiaceae plant species and has the following features: (1) comprehensive sequence annotations of 3663 genes 5959 RNAs, 22,723 ESTs and 11,438 regulatory sequence elements from Apiaceae and Alliaceae plant families; (2) graphical tools for visualization and analysis of sequence data; (3) access to traits, biosynthetic pathways, genetic linkage maps and molecular taxonomy data associated with Alliaceae and Apiaceae plants; and (4) comprehensive plant splice signal repository of 659,369 splice signals collected from 6015 plant species for comparative analysis of plant splicing patterns.
RoBuST, available at, provides an integrated platform for researchers to effortlessly explore and analyze genomic data associated with root and bulb vegetables.
PMCID: PMC3017783  PMID: 20691054
19.  The 2009 Lindau Nobel Laureate Meeting: Peter Agre, Chemistry 2003 
Peter Agre, born in 1949 in Northfield Minnesota, shared the 2003 Nobel Prize in Chemistry with Roderick MacKinnon for his discovery of aquaporins, the channel proteins that allow water to cross the cell membrane.
Agre's interest medicine was inspired by the humanitarian efforts of the Medical Missionary program run by the Norwegians of his home community in Minnesota. Hoping to provide new treatments for diseases affecting the poor, he joined a cholera laboratory during medical school at Johns Hopkins. He found that he enjoyed biomedical research, and continued his laboratory studies for an additional year after medical school.
Agre completed his clinical training at Case Western Hospitals of Cleveland and the University of North Carolina, and returned to Johns Hopkins in 1981. There, his serendipitous discovery of aquaporins was made while pursuing the identity of the Rhesus (Rh) antigen.
For a century, physiologists and biophysicists had been trying to understand the mechanism by which fluid passed across the cell's plasma membrane. Biophysical evidence indicated a limit to passive diffusion of water, suggesting the existence of another mechanism for water transport across the membrane. The putative "water channel," however, could not be identified.
In 1988, while attempting to purify the 30kDa Rh protein, Agre and colleagues began investigating a 28 kDa contaminant that they believed to be a proteolytic fragment of the Rh protein. Subsequent studies over the next 3-4 years revealed that the contaminant was a membrane-spanning oligomeric protein, unrelated to the Rh antigen, and that it was highly abundant in renal tubules and red blood cells. Still, they could not assign a function to it.
The breakthrough came following a visit with his friend and former mentor John Parker. After Agre described the properties of the mysterious 28 kDa protein, Parker suggested that it might be the long-sought-after water channel. Agre and colleagues tested this idea by expressing the protein in Xenopus oocytes, which typically have low water permeability. When the test oocytes were placed in a hypotonic solution, they swelled and exploded, thus revealing the function of the unknown protein as a water channel, which they named aquaporin.
The Nobel Prize enabled Agre to take his research and scientific interests in new directions. He felt that over the years his work had continually taken him further from his original interests in third-world diseases, so he shifted his focus back in that direction. He now serves as the director of the Malaria institute at Johns Hopkins where he has applied his knowledge to the study of the malarial parasite and the Anopheles mosquito, which both express aquaporins. In addition, since winning the Nobel Prize, he has enjoyed increased opportunities for bringing science to the public and for "encouraging young people to go into science."
PMCID: PMC3152244  PMID: 20010539
20.  Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer: a pilot study 
BMC Cancer  2011;11:389.
Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer.
Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre- and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6-minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded.
Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancer-specific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful.
These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work.
Trial registration
PMCID: PMC3189191  PMID: 21899778
Ovarian neoplasm; exercise; chemotherapy; feasibility
21.  Phenology, seasonal timing and circannual rhythms: towards a unified framework 
Phenology refers to the periodic appearance of life-cycle events and currently receives abundant attention as the effects of global change on phenology are so apparent. Phenology as a discipline observes these events and relates their annual variation to variation in climate. But phenology is also studied in other disciplines, each with their own perspective. Evolutionary ecologists study variation in seasonal timing and its fitness consequences, whereas chronobiologists emphasize the periodic nature of life-cycle stages and their underlying timing programmes (e.g. circannual rhythms). The (neuro-) endocrine processes underlying these life-cycle events are studied by physiologists and need to be linked to genes that are explored by molecular geneticists. In order to fully understand variation in phenology, we need to integrate these different perspectives, in particular by combining evolutionary and mechanistic approaches. We use avian research to characterize different perspectives and to highlight integration that has already been achieved. Building on this work, we outline a route towards uniting the different disciplines in a single framework, which may be used to better understand and, more importantly, to forecast climate change impacts on phenology.
PMCID: PMC2981940  PMID: 20819807
phenology; seasonal timing; circannual rhythms; reproductive physiology; molecular genetics; avian reproduction
22.  Effectiveness of Web-Based Versus Face-To-Face Delivery of Education in Prescription of Falls-Prevention Exercise to Health Professionals: Randomized Trial 
Exercise is an effective intervention for the prevention of falls; however, some forms of exercises have been shown to be more effective than others. There is a need to identify effective and efficient methods for training health professionals in exercise prescription for falls prevention.
The objective of our study was to compare two approaches for training clinicians in prescribing exercise to prevent falls.
This study was a head-to-head randomized trial design. Participants were physiotherapists, occupational therapists, nurses, and exercise physiologists working in Victoria, Australia. Participants randomly assigned to one group received face-to-face traditional education using a 1-day seminar format with additional video and written support material. The other participants received Web-based delivery of the equivalent educational material over a 4-week period with remote tutor facilitation. Outcomes were measured across levels 1 to 3 of Kirkpatrick’s hierarchy of educational outcomes, including attendance, adherence, satisfaction, knowledge, and self-reported change in practice.
Of the 166 participants initially recruited, there was gradual attrition from randomization to participation in the trial (n = 67 Web-based, n = 68 face-to-face), to completion of the educational content (n = 44 Web-based, n = 50 face-to-face), to completion of the posteducation examinations (n = 43 Web-based, n = 49 face-to-face). Participant satisfaction was not significantly different between the intervention groups: mean (SD) satisfaction with content and relevance of course material was 25.73 (5.14) in the Web-based and 26.11 (5.41) in the face-to-face group; linear regression P = .75; and mean (SD) satisfaction with course facilitation and support was 11.61 (2.00) in the Web-based and 12.08 (1.54) in the face-to-face group; linear regression P = .25. Knowledge test results were comparable between the Web-based and face-to-face groups: median (interquartile range [IQR]) for the Web-based group was 90.00 (70.89–90.67) and for the face-to-face group was 80.56 (70.67–90.00); rank sum P = .07. The median (IQR) scores for the exercise assignment were also comparable: Web-based, 78.6 (68.5–85.1), and face-to-face, 78.6 (70.8–86.9); rank sum P = .61. No significant difference was identified in Kirkpatrick’s hierarchy domain change in practice: mean (SD) Web-based, 21.75 (4.40), and face-to-face, 21.88 (3.24); linear regression P = .89.
Web-based and face-to-face approaches to the delivery of education to clinicians on the subject of exercise prescription for falls prevention produced equivalent results in all of the outcome domains. Practical considerations should arguably drive choice of delivery method, which may favor Web-based provision for its ability to overcome access issues for health professionals in regional and remote settings.
Trial Registration
Australian New Zealand Clinical Trials Registry number: ACTRN12610000135011; (Archived by WebCite at
PMCID: PMC3278102  PMID: 22189410
Education; professional development; course design; distance education; students
23.  FUNCTIONS OF VATA (BASED ON CHARAKA) A Passage from Vaatkalaakaleeyam 
Ancient Science of Life  1982;1(4):184-191.
The author has chosen 12th Chapter from the Sutra Sthana of this great epic containing 12,000 verses and passages which is replete with materials to revive the whole art of healing even if the whole medical literatures is lost. The passage puts in a nutshell the key role played by Vayu / Vata in the working of the tantra and yantra of the body. Though exploration of the humours is yet to be done by modern physiologists to explain the Ayurvedic Vata which is responsible to no less than 18 functions of the normal body mechanism
PMCID: PMC3336691  PMID: 22556488
24.  The lateral hypothalamus as integrator of metabolic and environmental needs: from electrical self-stimulation to opto-genetics 
Physiology & behavior  2011;104(1):29-39.
As one of the evolutionary oldest parts of the brain, the diencephalon evolved to harmonize changing environmental conditions with the internal state for survival of the individual and the species. The pioneering work of physiologists and psychologists around the middle of the last century clearly demonstrated that the hypothalamus is crucial for the display of motivated behaviors, culminating in the discovery of electrical self-stimulation behavior and providing the first neurological hint accounting for the concepts of reinforcement and reward. Here we review recent progress in understanding the role of the lateral hypothalamic area in the control of ingestive behavior and the regulation of energy balance. With its vast array of interoceptive and exteroceptive afferent inputs and its equally rich efferent connectivity, the lateral hypothalamic area is in an ideal position to integrate large amounts of information and orchestrate adaptive responses. Most important for energy homeostasis, it receives metabolic state information through both neural and humoral routes and can affect energy assimilation and energy expenditure through direct access to behavioral, autonomic, and endocrine effector pathways. The complex interplays of classical and peptide neurotransmitters such as orexin carrying out these integrative functions are just beginning to be understood. Exciting new techniques allowing selective stimulation or inhibition of specific neuronal phenotypes will greatly facilitate the functional mapping of both input and output pathways.
PMCID: PMC3131619  PMID: 21549732
Food intake; energy expenditure; leptin receptor; glucose sensing; orexin; MCH; reward seeking; obesity
25.  The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail 
BMC Gastroenterology  2012;12:60.
Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail.
GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (
This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping.
PMCID: PMC3464652  PMID: 22672254
Slow wave; Spike; Signal processing; Electrophysiology; Motility; Tachygastria

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