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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.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
doi:10.1093/humrep/deq155
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.
Background
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.
Conclusions
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
Background
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 http://dx.doi.org/10.1371/journal.pmed.1000110.
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)
doi:10.1371/journal.pmed.1000110
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.
doi:10.1002/cfg.277
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.
Highlights
► 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.
doi:10.1016/j.socscimed.2012.01.042
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.
doi:10.1371/journal.pone.0092005
PMCID: PMC3958414  PMID: 24642812
7.  Mild Traumatic Brain Injury and Executive Functions in School-Aged Children 
Developmental neurorehabilitation  2009;12(5):330-341.
Objective
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.
Results
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.
Discussion
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.
doi:10.3109/17518420903087251
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.
Images
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 http://sms.cam.ac.uk/media/1095515 (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.
doi:10.1186/1758-2946-3-34
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.
Background
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).
Discussion
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.
doi:10.1186/1471-2369-14-204
PMCID: PMC3850647  PMID: 24070232
Exercise; Resistance training; Hemodialysis; Dialysis; Stepped wedge; Cluster randomised control trial; Cost utility analysis; Exercise physiologist
12.  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
13.  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.
doi:10.1186/1743-0003-6-17
PMCID: PMC2698881  PMID: 19508711
14.  Correlates of time spent walking and cycling to and from work: baseline results from the commuting and health in Cambridge study 
Purpose
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.
Methods
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').
Results
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.
Conclusions
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.
doi:10.1186/1479-5868-8-124
PMCID: PMC3254135  PMID: 22074293
transport; active commuting; environmental perceptions; distance; Theory of Planned Behaviour
15.  Effectiveness of Web-Based Versus Face-To-Face Delivery of Education in Prescription of Falls-Prevention Exercise to Health Professionals: Randomized Trial 
Background
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.
Objective
The objective of our study was to compare two approaches for training clinicians in prescribing exercise to prevent falls.
Methods
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.
Results
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.
Conclusion
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; http://www.anzctr.org.au/ACTRN12610000135011.aspx (Archived by WebCite at http://www.webcitation.org/63MicDjPV)
doi:10.2196/jmir.1680
PMCID: PMC3278102  PMID: 22189410
Education; professional development; course design; distance education; students
16.  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
17.  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.
doi:10.1016/j.physbeh.2011.04.051
PMCID: PMC3131619  PMID: 21549732
Food intake; energy expenditure; leptin receptor; glucose sensing; orexin; MCH; reward seeking; obesity
18.  The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail 
BMC Gastroenterology  2012;12:60.
Background
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.
Results
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 (http://sites.google.com/site/gimappingsuite).
Conclusions
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.
doi:10.1186/1471-230X-12-60
PMCID: PMC3464652  PMID: 22672254
Slow wave; Spike; Signal processing; Electrophysiology; Motility; Tachygastria
19.  Career perspective: John B West 
I have been fortunate to work in two areas of extreme physiology and medicine: very high altitude and the microgravity of spaceflight. My introduction to high altitude medicine was as a member of Sir Edmund Hillary's Silver Hut Expedition in 1960–1961 when a small group of physiologists spent the winter and spring at an altitude of 5,800 m just south of Mt. Everest. The physiological objective was to obtain a better understanding of the acclimatization process of lowlanders during exposure to a very high altitude for several months. As far as we knew, no one had ever spent so long at such a high altitude before. The success of this expedition prompted me to organize the 1981 American Medical Research Expedition to Everest where the scientific objective was to determine the physiological changes that allow humans to survive in the extreme hypoxia of the highest point on earth. There is good evidence that this altitude is very near the limit of human tolerance to oxygen deprivation. Much novel information was obtained including an extraordinary degree of hyperventilation which reduced the alveolar partial pressure of carbon dioxide (Pco2) to about 8 mmHg (1.1 kPa) on the summit, and this in turn allowed the alveolar partial pressure of oxygen, PO2, to be maintained at a viable level of about 35 mmHg (4.7 kPa). The low Pco2 caused a severe degree of respiratory alkalosis with an arterial pH exceeding 7.7. These were the first physiological measurements to be made on the Everest summit, and essentially, none has been made since. The second extreme environment is microgravity. We carried out an extensive series of measurements on astronauts in the orbiting laboratory known as SpaceLab in the 1990s. Many aspects of pulmonary function are affected by gravity, so it was not surprising that many changes were found. However, overall gas exchange remained efficient. Some of the findings such as an anomalous behavior of inhaled helium and sulfur hexafluoride have still not been explained. Measurements made after astronauts were exposed to 6 months of microgravity in the International Space Station indicate that the function of the lung returns to its preexposure state within a few days.
doi:10.1186/2046-7648-1-11
PMCID: PMC3710103  PMID: 23849052
Extreme hypoxia; Hyperventilation; Maximal oxygen uptake; Distribution of blood flow; Pulmonary gas exchange; Microgravity
20.  From Bretonneau to therapeutic antibodies, from specificity to specific remedies, Saint-Cyr-Sur-Loire, France, November 19, 2012 
mAbs  2013;5(5):633-637.
Held on November 19, 2012 in Saint-Cyr-sur-Loire, France, the symposium “From Bretonneau to therapeutic antibodies, from specificity to specific remedies” focused on the historical development of antibodies as therapeutics, with an emphasis on the seminal work of the French physician Pierre-Fidèle Bretonneau (1778–1862). The morning session was devoted to discussion of the evolution of the concept of specificity in medicine, which started with an epistemological definition. The contributions of Bretonneau to the emergence of the concept of specificity, notably with his studies on diphtheria, and the subsequent development of antidiphtheric serotherapy in Europe during the period 1894–1898 were then presented in detail. The afternoon session began with a presentation on the role of French physiologists during the years 1860–1890 in establishing the basic concepts of specific immunity and the principles of serotherapy. The history of antivenom serotherapy, particularly its discovery by Césaire Phisalix, and the development of antilymphocyte globulins as successful transplantation drugs were then discussed. The symposium ended with the inauguration of a stele representing Bretonneau, who lived in Saint-Cyr-sur-Loire and died 150 y ago.
doi:10.4161/mabs.25613
PMCID: PMC3851214  PMID: 23924799
immunospecificity history; serotherapy history; Bretonneau; Pierre (1778-1862); history of medicine; 19th century and 20th century
21.  Physiological Responses to 90 s All Out Isokinetic Sprint Cycling in Boys and Men 
The purpose of this study was to compare the VO2 kinetic and mechanical power responses of boys and men to all out 90 s sprint cycle exercise. Eight boys (14.6 ± 0.3 y) and eight men (33.8 ± 6.5 y) volunteered to participate and completed a ramp test (to determine VO2peak and ventilatory threshold, VT) and then on subsequent days, two 90 s all out cycle sprints on an isokinetic cycle ergometer. During each test, breath-by-breath pulmonary gas exchange and power output were measured. Parameters from the power output profiles were derived from the average response of the two tests including peak power (PP, highest power output in 1 s), end power (EP60-90, power over the last 30 s), and mean power over the 90 s (MP90). Independent pairwise and dependent t-tests were used to compare the data from tests between adults and boys subject groups. Significant differences between adults and boys were found for absolute PP (881.4 ± 60.7 vs 533.6 ± 50.7 W), EP60-90 (288.6 ± 25.7 vs 134.3 ± 17.6 W) and MP90 (434.5 ± 27.4 vs 238.4 ± 17.3 W, p =0.001) respectively. Relative to body mass significant differences between adults and boys were found for EP60-90, MP90 and total work (p < 0.002). The boys attained 90 s VO2 values that were closer to VO2peak than their adult counterparts (93.3 ± 2.6 vs 84.9 ± 2.3 %, p = 0.03). They also demonstrated faster VO2 kinetics (10.8 ± 1.5 vs 17.6 ± 1.0 s, p < 0.01). In conclusion, during all out 90 s cycle sprinting boys were able to attain VO2 values that were closer to VO2peak and a faster time constant than adult men. These findings provide insight into the contribution and speed of response of the aerobic system during an ‘anaerobic’ test.
Key PointsThe results of this study confirm the significant contributions of the aerobic energy systems during so called ‘anaerobic tests’.Boys were able to attain VO2 values from an all out 90 s sprint cycle that were closer to their aerobic VO2 peak test than adults. More detailed studies are required to investigate the limiting factors that prevent VO2 peak being reached in an all out sprint cycle.All out tests of a duration > 30 s and coupled with gas and power analyses offer paediatric physiologists considerable scope to examine the contributions of the anaerobic and aerobic energy systems until more ethically viable methods are found.
PMCID: PMC3899660  PMID: 24501558
VO2peak; anaerobic; kinetics; aerobic; ergometry
22.  Adolf Beck: A pioneer in electroencephalography in between Richard Caton and Hans Berger 
Advances in Cognitive Psychology  2013;9(4):216-221.
Adolf Beck, born in 1863 in Kraków (Poland), joined the Department of Physiology of the Jagiellonian University in 1889, to work directly under the prominent professor in physiology Napoleon Cybulski. Following his suggestion, Beck started studies on the electrical brain activity of animals. He recorded negative electrical potentials in several brain areas evoked by peripheral sensory impulses. Using this technique, Beck localised various centres in the brain of several animal species. In doing this, he discovered continuous electrical oscillations in the electrical brain activity and noted that these oscillations ceased after sensory stimulation. This was the first description of desynchronization in electrical brain potentials. He published these findings in 1890 in the German Centralblatt für Physiologie. Immediately, an intense discussion arose under physiologists on the question who could claim being the founder of electroencephalography. Ultimately, Richard Caton from Liverpool showed that he had performed similar experiments in monkeys years earlier. Nevertheless, Beck added several new elements to the nature of electrical brain activity, such as evoked potentials and desynchronization. In looking back, Adolf Beck can be regarded, next to Richard Caton and together with Hans Berger (who later introduced the electrical brain recording method to humans), as one of the founders of electroencephalography.
doi:10.2478/v10053-008-0148-3
PMCID: PMC3902832  PMID: 24605179
Adolf Beck; pioneer in electroencephalography; spontaneous oscillations; evoked potentials; desynchronization of brain waves; Richard Caton; Hans Berger
23.  Korotkoff Sounds - The Improbable also Occurs 
Arquivos Brasileiros de Cardiologia  2013;101(5):e99-e100.
Very few discoveries have had such a large impact on and relevance to clinical medicine as the noninvasive measurement of the diastolic blood pressure. A number of gifted physiologists and clinicians were ineffectively in search of a noninvasive method to determine the diastolic pressure. Nonetheless, the quantification of the diastolic BP was not achieved by any of these clinical or physiological researchers, but by an unlikely and unexpected figure: Nikolai Sergeevich Korotkoff (1874-1920), a young Russian army surgeon, working under precarious conditions in the hardship of diverse wars. It is easy to dismiss the achievement of Korotkoff as a serendipitous discovery, similar to that of Alexander Fleming in the discovery of penicillin. However, Nassim N. Taleb's recent black swan theory may serve to illustrate his discovery in a new and, perhaps, surprising way.
doi:10.5935/abc.20130217
PMCID: PMC4081176  PMID: 24343557
History of Medicine; Arterial Pressure; Sphygmomanometers / utilization
24.  Mechanistic modeling confronts the complexity of molecular cell biology 
Molecular Biology of the Cell  2014;25(22):3494-3496.
Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist–electrical engineer–systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build—and subject to exhaustive experimental tests—models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.
doi:10.1091/mbc.E14-08-1333
PMCID: PMC4230610  PMID: 25368428
25.  Lactate: A key metabolite in the intercellular metabolic interplay 
Critical Care  2002;6(4):284-285.
Most physicians involved in intensive care consider lactate solely as a deleterious metabolite, responsible for high morbidity and bad prognosis in severe patients. For the physiologist, however, lactate is a key metabolite, alternatively produced or consumed. Many studies in the literature have infused animals or humans with exogenous lactate, demonstrating its safety and usefulness, but the bad reputation of lactate is still widespread. The metabolic meaning of glucose–lactate cycling exceeds its initial role described by Cori and Cori. According to recent works concerning lactate, it can be predicted that a new role as a therapeutic agent will arise for this metabolite.
PMCID: PMC137304  PMID: 12225597
brain; Cori cycle; exogenous substrate; kidney; lung; metabolic shuttle

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