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Previous reports of substantial inter-individual differences in weight change following an exercise intervention are often based solely on the observed responses in the intervention group. Therefore, we aimed to quantify the magnitude of inter-individual differences in exercise-mediated weight change. We synthesized randomized controlled trials (RCTs) of structured, supervised exercise interventions. Fourteen electronic databases were searched for relevant studies published up to March 2017. Search terms focused on structured training, RCTs and body weight. We then sifted these results for those RCTs (n = 12, 1500 participants) that included relevant comparator group data. Standard deviations (SDs) of weight change were extracted, thereby allowing the SD for true inter-individual differences in weight loss to be calculated for each study. Using a random effects meta-analysis, the pooled SD (95% CI) for true individual responses was 0.8 (-0.9 to 1.4) kg. The 95% prediction interval (based on 2SDs) for true inter-individual responses was -2.8 to 3.6 kg. The probability (% chance) that the true individual response variability would be clinically meaningful (>2.5 kg) in a future study in similar settings was 23% ('unlikely'). Therefore, we conclude that evidence is limited for the notion that there are clinically important individual differences in exercise-mediated weight change.

McLay et al. (Clin Physiol Funct Imaging (2017); DOI: 10.1111/cpf.12465) recently examined whether the allometric scaling of flow-mediated dilation influenced the mean difference between samples of young and older adults compared with the traditional percentage change approach. They also explored whether a new scaling calculation improved the ability to obtain individually scaled flow-mediated dilation. In our response to their study, we can demonstrate that McLay et al. (Clin Physiol Funct Imaging, 2017) have (i) managed to formulate a new scaling index which does nothing to remove the dependency of that index on baseline diameter and (ii) suggested, incorrectly, that the original allometric approach cannot be used to derive individually-adjusted values of flow-mediated dilation, which can be interpreted in a similar way to a percentage change.

Obese adults and children can be referred to lifestyle weight management services (LWMS) in which physical activity and/or dietary advice are delivered. Service providers quantify the 'weight' change between an initial measurement and follow-up measurement(s), which could be 12-24 months later. A control group is usually absent. The aim of this article is to scrutinise the various LWMS objectives for this weight change that are recommended by UK authorities. UK guidelines recommend that an adult LWMS should (A) reduce the sample mean body mass of all enrolled adults by at least 3% and/or (B) reduce the body mass of at least 30% of adults by at least 5%. We highlight the potential for objective B to be met even if no LWMS is implemented, especially over the recommended follow-up periods of 12-24 months. This is due to unavoidable random within-participant fluctuations in weight over such periods of time. A ≥1 kg reduction in mean body mass is also to be expected, even without any LWMS. Therefore, we suggest that objectives A and B are too liberal. Obesity status in children is indicated by the body mass index (BMI) z-score. Nevertheless, another UK recommendation is for an LWMS to "maintain" or "reduce" the BMI z-score of 80% of the enrolled children. Besides there being no stated thresholds for "maintain" and "reduce", it is inconceivable to deem an LWMS successful even if 80% of children do not alter their obesity status and even if the remaining 20% of children actually increase their obesity status. Here, we think the BMI z-score has been confused with the body mass z-score. In conclusion, measurable objectives of UK-based LWMS need to be clarified, and possibly altered, to account for typical amounts of random variability in individual weight measurements over the service time period.

Purpose:To quantify the mean daily changes in training and match load and any parallel changes in indicators of morningmeasured fatigue across in-season training weeks in elite soccer players.Methods:After each training session and match (TL), session ratings of perceived exertion (s-RPE) were recorded to calculate overall session load (RPE-TL) in 29 English Premier League players from the same team. Morning ratings of fatigue, sleep quality, and delayed-onset muscle soreness (DOMS), as well as submaximal exercise heart rate (HRex), postexercise heart-rate recovery (HRR%), and heart-rate variability (HRV) were recorded before match day and 1, 2, and 4 d postmatch. Data were collected for a median duration of 3 wk (range 1–13) and reduced to a typical weekly cycle including no midweek match and a weekend match day. Data were analyzed using withinsubject linear mixed models.Results:RPE-TL was approximately 600 arbitrary units (AU) (95% confidence interval 546–644) higher on match day than following day (P < .001). RPE-TL progressively decreased by »60 AU per day over the 3 days before a match (P < .05). Morning-measured fatigue, sleep quality, and DOMS tracked the changes in RPE-TL, being 35–40% worse on postmatch day vs prematch day (P < .001). Perceived fatigue, sleep quality, and DOMS improved by 17–26% from postmatch day to 3 d postmatch, with further smaller (7%–14%) improvements occurring between 4 d postmatch and prematch day (P < .01). There were no substantial or statistically significant changes in HRex, HRR%, or HRV over the weekly cycle (P > .05).Conclusions:Morning-measured ratings of fatigue, sleep quality, and DOMS are clearly more sensitive than HR-derived indices to the daily fluctuations in session load experienced by elite soccer players in a standard in-season week.

Radiological anatomy education is an important aspect of the medical curriculum. The purpose of this study was to establish and demonstrate the use of plastinated anatomical specimens, specifically human hearts, for use in radiological anatomy education. Four human hearts were processed with routine plastination procedures at room temperature. Specimens were subjected to cone beam computed tomography and a graphics program (ER3D) was applied to generate 3D cardiac models. A comparison was conducted between plastinated hearts and their corresponding computer models based on a list of morphological cardiac features commonly studied in the gross anatomy laboratory. Results showed significant correspondence between plastinations and CBCT-generated 3D models (98 %; p

A post-menopausal hot flush consists of profuse physiological elevations in cutaneous vasodilatation and sweating that are accompanied by reduced brain blood flow. These responses can be used to objectively quantify hot flush severity. The impact of an exercise training intervention on the physiological responses occurring during a hot flush is currently unknown. In a preference-controlled trial involving 21 post-menopausal women, 16 weeks of supervised moderate intensity exercise training was found to improve cardiorespiratory fitness and attenuate cutaneous vasodilatation, sweating and the reductions in cerebral blood flow during a hot flush. It is concluded that the improvements in fitness that are mediated by 16 weeks of exercise training reduce the severity of physiological symptoms that occur during a post-menopausal hot flush. A hot flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilatation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilatation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot flushes at baseline and follow-up. Fourteen participants opted for a 16 week moderate intensity supervised exercise intervention, while seven participants opted for control. Sweat rate, cutaneous vasodilatation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot flush sweat rate decreased by 0.04 mg cm(2) min(-1) at the chest (95% confidence interval 0.02-0.06, P = 0.01) and by 0.03 mg cm(2) min(-1) (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilatation by 9% (6-12%) at the chest and by 7% (4-9%) at forearm (P ≤ 0.05). Training attenuated hot flush MCAv by 3.4 cm s(-1) (0.7-5.1 cm s(-1) , P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot flushes by 109 arbitrary units (80-121, P < 0.001). These data indicate that exercise training leads to parallel reductions in hot flush severity and within-flush changes in cutaneous vasodilatation, sweating and cerebral blood flow.

New Findings What is the topic of this review? In ‘personalized medicine’, various plots and analyses are purported to quantify individual differences in intervention response, identify responders/non-responders and explore response moderators or mediators. What advances does it highlight? We highlight the impact of within-subject random variation, which is inevitable even with ‘gold-standard’ measurement tools/protocols and sometimes so substantial that it explains all apparent individual response differences. True individual response differences are quantified only by comparing the SDs of changes between intervention and comparator arms. When these SDs are similar, true individual response differences are clinically unimportant and further analysis unwarranted. Within the ‘hot topic’ of personalized medicine, we scrutinize common approaches for presenting and quantifying individual differences in the physiological response to an intervention. First, we explain how popular plots used to present individual differences in response are contaminated by random within-subject variation and the regression to the mean artefact. Using a simulated data set of blood pressure measurements, we show that large individual differences in physiological response can be suggested by some plots and analyses, even when the true magnitude of response is exactly the same in all individuals. Second, we present the appropriate designs and analysis approaches for quantifying the true interindividual variation in physiological response. It is imperative to include a comparator arm/condition (or derive information from a prior relevant repeatability study) to quantify true interindividual differences in response. The most important statistic is the SD of changes in the intervention arm, which should be compared with the same SD in the comparator arm or from a prior repeatability study in the same population conducted over the same duration as the particular intervention. Only if the difference between these SDs is clinically relevant is it logical to go on to explore any moderators or mediators of the intervention effect that might explain the individual response. To date, very few researchers have compared these SDs before making claims about individual differences in physiological response and their importance to personalized medicine.

Left ventricular ejection fraction (EF) is a ratio that is deemed to accurately normalize stroke volume (SV) to end-diastolic volume (EDV). Ratios are now well-recognized for not normalizing the numerator, in this case SV, consistently for the denominator, EDV. We aimed to provide the first allometric-based scrutiny of the conventional assumptions that underpin the EF ratio. We allometrically modelled untransformed SV and EDV measurements from 112 preclinical heart failure patients in the Multi-Ethnic Study of Atherosclerosis (MESA), and 864 chronic heart failure patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. An information-theoretic approach was adopted to assess the relative quality of twelve candidate models for normalizing SV to EDV. None of the conventional underlying assumptions for accurate ratio normalization, for example an allometric exponent ≈1, were upheld for EF. A two-parameter power function with normal, heteroscedastic error was the best model for scaling SV to EDV in both samples. The allometric exponent (95% confidence interval) was 0·776 (0·682 to 0·869) in MESA, and 0·860 (0·857 to 0·864) in TOPCAT. EF was inversely correlated with EDV in MESA (r = -0·67, 95% CI: -0·76 to -0·55) and TOPCAT (r = -0·41, 95% CI: -0·46 to -0·35). Consequently, for fundamental statistical reasons, EF was biased low for people with generally larger EDVs, and vice versa. For the first time, we have demonstrated that EF is an inaccurate statistic for scaling SV to EDV, leading to potential biased inferences for research and individual patients.

The monitoring of training loads is now a much-researched topic in team sports.1 Within this topic, researchers and practitioners are particularly interested in the impact of relatively short (acute) periods of higher training loads normalised for the prior and longer term (chronic) loads. In recent years, a well-established approach for normalising this acute ‘spike’ to chronic load has been by calculating the ‘acute:chronic workload ratio’ (ACWR). Importantly, the term "load" was retained given its common use in this research area. Both this index and chronic load itself have been reported to be independent predictors of training-related injuries.2 It has also been reported, particularly in team sports competitors, that there are associations between acute spikes in training loads (relative to chronic loads) and time-loss injuries.1 The ACWR is usually calculated as the simple ratio of recent (ie, 1 week) to longer term (ie, 4 weeks) training loads.1 While it is important for the numerator and denominator of any ratio to be correlated only through biological mechanisms,3 one aspect of the ACWR calculation is that the acute load also constitutes a substantial …

Recent laboratory experiments on rodents have increased our understanding of circadian rhythm mechanisms. Typically, circadian biologists attempt to translate their laboratory-based findings to treatment of jet lag symptoms in humans. We aimed to scrutinise the strength of the various links in the translational pathway from animal model to human traveller. First, we argue that the translation of findings from pre-clinical studies to effective jet lag treatments and knowledge regarding longer-term population health is not robust, e.g. the association between circadian disruption and cancer found in animal models does not translate well to cabin crew and pilots, who have a lower risk of most cancers. Jet lag symptoms are heterogeneous, making the true prevalence and the effects of any intervention difficult to quantify precisely. The mechanistic chain between in vitro and in vivo treatment effects has weak links, especially between circadian rhythm disruption in animals and the improvement of jet lag symptoms in humans. While the number of animal studies has increased exponentially between 1990 and 2014, only 1-2 randomised controlled trials on jet lag treatments are published every year. There is one relevant Cochrane review, in which only 2-4 studies on melatonin, without baseline measures, were meta-analysed. Study effect sizes reduced substantially between 1987, when the first paper on melatonin was published, and 2000. We suggest that knowledge derived from a greater number of human randomised controlled trials would provide a firmer platform for circadian biologists to cite jet lag treatment as an important application of their findings.

A ratio index (FMD%) is used ubiquitously to scale (by simple division) brachial artery flow-mediated dilation (Ddiff) in direct proportion to baseline diameter (Dbase). It is now known that Ddiff is inversely proportional to Dbase rendering FMD% wholly inappropriate. Consequently, FMD% is still substantially dependent on Dbase. Although this problem is grounded in statistics, normalization of FMD% for the change in arterial shear rate (ΔSR) has been proposed to remove this Dbase-dependency. It was hypothesized that, if the flow-mediated response is scaled properly to Dbase in the first place, shear rate normalization would not be needed to remove Dbase-dependency. Dedicated software (Digitizelt) was employed to extract the data from a seminal study on FMD% normalization. The underlying allometric relationship between Dbase and peak diameter (Dpeak) was described. The re-analyses revealed that the absolute change in arterial diameter was strongly inversely proportional to Dbase (r= − 0.7, P

BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences.OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents.SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions.SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information.MAIN RESULTS: We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m(2) (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children.AUTHORS' CONCLUSIONS: This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.

Two-point discrimination is measured as an indicator of cortical reorganisation in musculoskeletal medicine. Nevertheless, data are lacking for the reliability of this measure in patients with non-specific chronic low back pain (NSCLBP). We aimed to quantify the intra- and inter-observer reliability of a novel protocol for measuring two-point discrimination in these patients. 35 participants (12 males, 23 females, mean age 52, SD 15 years) with NSCLBP were recruited. Three clinicians made 14 consecutive measurements of two-point discrimination with callipers. One of these clinicians repeated the assessment protocol within 7 d. During each measurement, the calliper width was widened in 5 mm increments until participants could consistently identify two points. Intra- and inter-observer agreement was quantified using mean difference, within-subject SD and limits of agreement (LOA). After using the first measurement for familiarisation, the mean of measurements 2–5 within an assessment resulted in the optimum compromise between clinic time constraints and acceptable intra-observer reliability; the within-subjects SD being 7.5 mm (LOA: 20.8 mm). Inter-observer reliability was generally poorer; requiring the mean of measurements 2–9 within an assessment for a similar within-subjects SD of 8.6 mm (LOA: 23.7 mm). It was estimated that these within-subjects SDs were small enough for a clinically-important change to be detected with a feasible sample size in future studies. The intra-observer reliability of our assessment protocol is acceptable for detecting a clinically relevant difference in two-point discrimination for future research purposes. Nevertheless, individual patient measurement variability is relatively high, especially between different clinicians.

The percentage flow-mediated dilation (FMD%) of the brachial artery is purported to be an early indicator of atherosclerosis and has been reported to be reduced in people with obstructive sleep apnoea. Nevertheless, FMD% scales poorly for, and is concomitantly dependent on, initial artery diameter, which may, itself, be higher in obstructive sleep apnoea patients. Therefore, for the first time, we aimed to quantify the differences in initial diameter and properly scaled flow-mediated dilation between people with and without sleep apnoea.The prevalence of physician-diagnosed sleep apnoea, as well as initial and peak diameters of the brachial artery were recorded for 3354 participants in the Multiethnic Study of Atherosclerosis (MESA). Arterial data were analysed using FMD% and an allometric approach, which scales the flow-mediated response properly for initial diameter.In the sex, race and age-adjusted model, initial diameter was 0.19 mm larger in sleep apnoea patients [95% confidence interval (CI): 0.07 to 0.32 mm, P = 0.003] and correlated negatively with FMD% (r = -0.43, 95% CI: -0.57 to -0.26, P 0.0005). Using this same adjusted model, FMD% was 3.8 ± 2.7% for sleep apnoea patients (n = 104) versus 4.4 ± 2.7% for undiagnosed people (95% CI for difference: -1.12 to -0.07%, P = 0.028). Allometric scaling halved this FMD%-indicated sample difference in flow-mediated dilation (95% CI: -0.7 to 0.1%, P = 0.19).The initial diameter of the brachial artery is larger in MESA participants diagnosed with sleep apnoea compared with undiagnosed people. However, the difference in flow-mediated dilation between these two cohorts is trivial, when the flow-mediated response is scaled properly for resting diameter.

Background/Objective: There are reports that childhood obesity tracks into later life. Nevertheless, some tracking statistics such as correlations do not quantify individual agreement, whereas others such as diagnostic test statistics can be difficult to translate into practice. We aimed to employ a novel analytic approach, based on ordinal logistic regression, to predict weight status of 11-year-old children from measurements at age 5 years. Subjects/Methods: The UK 1990 growth references were used to generate clinical weight status categories of 12 076 children enrolled in the Millennium Cohort Study. Using ordinal regression, we derived the predicted probability (percent chances) of 11-year-old children becoming underweight, normal weight, overweight, obese and severely obese from their weight status category at age 5 years. Results: The chances of becoming obese (including severely obese) at age 11 years were 5.7% (95% confidence interval: 5.2 to 6.2%) for a normal-weight 5-year-old child and 32.3% (29.8 to 34.8%) for an overweight 5-year-old child. An obese 5-year-old child had a 68.1% (63.8 to 72.5%) chance of remaining obese at 11 years. Severely obese 5-year-old children had a 50.3% (43.1 to 57.4%) chance of remaining severely obese. There were no substantial differences between sexes. Nondeprived obese 5-year-old boys had a lower probability of remaining obese than deprived obese boys: −21.8% (−40.4 to −3.2%). This association was not observed in obese 5-year-old girls, in whom the nondeprived group had a probability of remaining obese 7% higher (−15.2 to 29.2%). The sex difference in this interaction of deprivation and baseline weight status was therefore −28.8% (−59.3 to 1.6%). Conclusions: We have demonstrated that ordinal logistic regression can be an informative approach to predict the chances of a child changing to, or from, an unhealthy weight status. This approach is easy to interpret and could be applied to any longitudinal data set with an ordinal outcome.

Background Child and adolescent overweight and obesity have increased globally, and are associated with significant short and long term health consequences. Objectives To assess the effects of surgical interventions for treating obesity in childhood and adolescence. Search methods We searched the Cochrane Library, MEDLINE, PubMed, EMBASE as well as LILACS, ICTRP Search Portal and ClinicalTrials.gov (all from database inception to March 2015). References of identified studies and systematic reviews were checked. No language restrictions were applied. Selection criteria We selected randomised controlled trials (RCTs) of surgical interventions for treating obesity in children and adolescents (age < 18 years) with a minimum of six months follow-up. Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded. Pregnant females were also excluded. Data collection and analysis Two review authors independently assessed risk of bias and extracted data. Where necessary authors were contacted for additional information. Main results We included one RCT (a total of 50 participants, 25 in both the intervention and comparator group). The intervention focused on laparoscopic adjustable gastric banding surgery, which was compared to a control group receiving a multi component lifestyle programme. The participating population consisted of Australian adolescents (a higher proportion of girls than boys) aged 14 to 18 years, with a mean age of 16.5 and 16.6 years in the gastric banding and lifestyle group, respectively which was conducted in a private hospital, receiving funding from the gastric banding manufacturer. The study authors were unable to blind participants, personnel and outcome assessors which may have resulted in a high risk of performance and detection bias. Attrition bias was noted as well. The study authors reported a mean reduction in weight of 34.6 kg (95% confidence interval (CI) 30.2 to 39.0) at two years, representing a change in body mass index (BMI) of 12.7 (95% CI 11.3 to 14.2) for the surgery intervention; and a mean reduction in weight of 3.0 kg (95% CI 2.1 to 8.1) representing a change in BMI of 1.3 (95% CI 0.4 to 2.9) for the lifestyle intervention. The differences between groups were statistically significant for all weight measures at 24 months (P < 0.001). The overall quality of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was low. Adverse events were reported in 12/25 (48%) participants in the intervention group compared to 11/25 (44%) in the control group (low quality evidence). A total of 28% of the adolescents undergoing gastric banding required revisional surgery. No data were reported for all-cause mortality, behaviour change, participants views of the intervention and socioeconomic effects. At two years, the gastric banding group performed better than the lifestyle group in two of eight health-related quality of life concepts (very low quality evidence) as measured by the Child Health Questionnaire (physical functioning score (94 versus 78, community norm 95) and change in health score (4.4 versus 3.6, community norm 3.5)). Authors' conclusions Laparoscopic gastric banding led to greater body weight loss compared to a multi component lifestyle program in one small study with 50 patients. These results do not provide enough data to assess efficacy across populations from different countries, socioeconomic and ethnic backgrounds, who may respond differently. This systematic review highlights the lack of RCTs in this field. Future studies should assess the impact of the surgical procedure and post operative care to minimise adverse events, including the need for post operative adjustments and revisional surgery. Long-term follow-up is also critical to comprehensively assess the impact of surgery as participants enter adulthood.

In 2010, the American College of Cardiology Foundation and American Heart Association could not recommend brachial artery percentage flow-mediated dilation (FMD%) for risk assessment of coronary artery disease (CAD) in asymptomatic adults. We aimed to scrutinise past and recently published findings regarding FMD% in this same context of clinical utility and conclude that (1) the question of whether brachial FMD% is a suitable substitute for coronary vasodilation is addressed by method agreement statistics rather than the correlation coefficients that have been reported in past studies. Also, the much-repeated view that brachial FMD% and coronary vasodilation are “closely related” is not entirely justified, even before the influence of baseline lumen diameters on this relationship is accounted for; (2) along with the specialist training and the considerable time (≥1 h) that is required for the FMD% protocol, the error in individual measurements and population reference ranges is too large for clinical decisions to be robust on individual patients; (3) many interventions that are proposed to change FMD% also change baseline artery diameter, which can bias estimates of any intervention effects on the flow-mediated response per se, and (4) the FMD% index generates spurious correlations between shear rate, artery diameter and endothelial function, which may help to explain the apparent paradoxes of FMD% being higher in obese people and lower in athletes. In conclusion, the clinical relevance of brachial artery flow-mediated dilation is unclear at present. The dependence of the chosen index, FMD%, on initial artery size has contributed to this lack of clarity.

We investigated the effects of evening bright light on the circadian timing of core temperature and morning exercise performance under conditions of high thermal stress. At 20:00 h, 8 males were exposed to a standardised light protocol and thereafter to either polychromatic bright light (2 500 lux at 50 cm, BL) or no light (0 lux, NL) for 30 min. The following morning, intermittent cycling exercise was undertaken followed by a 10 km time-trial in an environmental chamber set to 35°C and 60% relative humidity. Core body temperature was measured throughout. Data were analysed using a within-subjects model and presented as mean±SD. Time of the sleep-trough in core temperature occurred ~1.75 h later following BL (P=0.07). Prior to time-trial, core temperature was 0.27±0.42°C lower in BL (95%CI: −0.02 to 0.57, P=0.07). The time-trial was completed 1.43±0.63 min (0.98–1.87) faster in BL (P=0.001). Post time-trial, intestinal temperature was 38.21±0.56°C (37.84–38.57) in BL compared to 38.64±0.42°C (38.34–38.93) in NL (P=0.10). These data provide the first evidence that a 30-min exposure to bright light prior to sleep can influence exercise performance under hot conditions during the subsequent early morning.

Schubert et al. [1] systematically reviewed studies on the acute effects of exercise on hormones related to appetite regulation. A meta-analysis was incorporated to quantify the pooled effect sizes (and corresponding 95 % confidence intervals) for the difference in area-under-the-curve responses between an exercise condition and a control (noexercise) condition. The meta-analysis of crossover studies is not straightforward. Elbourne et al. [2] discussed the various options for meta-analysing crossover designs. The least preferable option was to ignore the crossover nature of the design and, thereby, disregard the paired (within-subjects) nature of the data. In this approach, the effect sizes are meta-analysed as if the study designs are two-group, randomised, controlled trials. This approach was deemed to violate the assumption of case independence and to be too conservative [2]. We wonder to what extent Schubert et al. [1] accounted for the crossover nature of the studies? For example, there was no information regarding the imputation of a paired correlation coefficient in the meta-analysis to arrive at standard errors and confidence intervals that reflect the crossover nature of the study designs. In many of the reviewed studies (e.g. 3), the difference in area-under-the-curve ghrelin between exercise and control trials was reported by the original study authors to be statistically significant. Nevertheless, the 95 % confidence intervals calculated in [1] overlap zero for all but 1 of the 25 studies on ghrelin (see forest plot). In the supplementary file [1], the associated P values are calculated to be not statistically significant for all but one of the studies on ghrelin. Perhaps this discrepancy could be because the paired nature of the data at the individual study level has been overlooked, resulting in confidence intervals and P values for the overall and subgroup effect sizes that are biased wide and high, respectively.

To examine the effects of a simulated dawn during the last 30 min of sleep on the subsequent dissipation of sleep inertia and changes in simulated work and physical performance. Eight participants, who reported difficulty with morning waking, were administered in a random order to a control (C) and a dawn simulation (DS) trial (starting 30 min prior to waking). Subjective ratings of sleep quality and alertness were obtained alongside measures of cognitive performance (addition and reaction time tasks measured at 5, 30 and 75 min after waking at habitual workday times). Physical performance was also measured 35 min after waking using a self-paced cycling protocol. After waking in DS, perceived sleep quality was 1.16 ± 0.89 (p = 0.01) points higher compared with C. Ratings of alertness were significantly higher in DS than C throughout the testing period (p = 0.04). Cognitive performance improved in both trials as time awake increased (p

The aim of the present study was to determine the between-match variability in soccer referees' match performances. 1 269 individual match observations were undertaken on 59 referees (range 2-79 games per referee) officiating in the English Premier League and Championship from 2003/2004 to 2007/2008 using a computerised tracking system (Prozone (®), Leeds, England). Between-match coefficients of variation (CV) were calculated for all games and then compared between referee age and experience groups. High mean CVs were observed for high-speed running distance (25.9±10.1%), recovery time (32.7±13.8%), explosive sprints (34.3±16.6%), total number of sprints (54.0±20.7%) and number of match fouls (28±4.6%). Smaller CVs were observed for total distance covered (3.8±1.5%), top sprinting speed (5.6±10.9%), distance from the ball (4.2±1.9%) and the distance from fouls (9.9±4.3%). Variability in match activities was not influenced by referee age or experience. The present study's findings demonstrate that variability in soccer referees' match performances is high in some variables and not dependent on referee age or experience. Such variability means that research requires large sample sizes to detect real systematic changes in a number of performance characteristics when studied during matches.

Low pressure turbine blades in power stations suffer from leading edge erosion damage due to water impingement. In an effort to extend the life of these blades, repair of the eroded regions has been proposed using laser cladding with Stellite material. However, the addition of Stellite results in residual stresses being generated in the parent metal due to contraction during cooling and differences in thermal expansion between the two materials. In this work test coupons and laser clad blades were examined for residual stresses using both the L3 diffractometer at the NRU reactor, Chalk River, Canada and the TASS strain scanner at ANSTO's HIFAR reactor, Lucas Heights, Australia. In addition XRD results were used to measure residual stresses on the surface of the blade to complement the neutron measurements. An FEA model of a simplified weld was used to explain some of the results., 134th TMS Annual Meeting & Exhibition, 13-17 February 2005, San Francisco, USA

The pyrochlore based bismuth stannate, Bi2Sn2O 7, is a material with important applications in catalysis and gas sensing. The thermodynamically stable α phase has 352 atoms in the unit cell and is one of the most complex oxide crystal structures to have been solved by powder diffraction. We have performed a full atomic relaxation and calculated the electronic structure, using gradient corrected density functional theory, with the resulting structure in very good agreement with the previous experimentally determined unit cell. The computed density of states is in excellent agreement with our valence band X-ray photoelectron spectra. The combined results shed new light on the bonding and lone pair activity in this material. A mixture of Bi 6s and O 2p states are found to dominate the top of the valence band while Sn 5s, O 2p and Bi 6p states dominate the bottom of the conduction band. The differing contributions of Sn 5s and Bi 6s states to the valence and conduction bands reflect both differences in atomic binding energies and differences in the strength of the metal s interactions with O 2p. The preference of this material for a distorted structure and its unique catalytic and gas sensing activity are discussed. © The Royal Society of Chemistry 2006.

Generally, swimmers pace themselves using their own judgement and the poolside clock during swimming training, fitness testing protocols or scientific investigation. The Aquapacer is a new pacing device that can be used to pace the swimming speed or stroke rate of the swimmer. The aims of this study were to determine if breaststroke swimmers could pace accurately during submaximal swimming using a poolside clock (Study 1) and the Aquapacer (Study 2), at swimming speeds at, just above and just below maximal 200 m time-trial speeds (using the Aquapacer, Study 3) and under three different race pacing conditions (using the Aquapacer, Study 4). Between 8 and 15 male national or club standard 200 m breaststroke swimmers participated in each of the studies. The swimmers in Study 2, despite being less well trained than the swimmers in Study 1 and part of a more heterogeneous group in terms of swimming performance, repeatedly demonstrated less random error in pacing, suggesting that the Aquapacer may be preferable to the poolside clock when swimmers are being required to pace accurately. The Aquapacer also enabled swimmers to pace accurately at race-specific swimming speeds (until fatigue precluded them from holding pace) (Study 3), and through a change in pace at race-specific speeds (Study 4), which suggests that it may be of use in entraining racing strategies.

Sleep-disordered breathing is an important comorbidity for several diseases, including stroke. Initial screening tools comprise simple yes/no questions about known risk factors for sleep-disordered breathing, e.g., obesity, sex. But walking speed has not been investigated in this context. We examined the cross-sectional association between walking pace and sleep-disordered breathing in the population-level Multi-Ethnic Study of Atherosclerosis. A sample of 2912 men and 3213 women (46-87 years) reported perceived walking pace outside their homes. A walking pace0.89 m/s was deemed "slow", with ≥ 0.89 m/s considered "average/brisk" according to validated thresholds. Sample prevalences were: sleep apnoea (3.5%), self-reported apnoeas (8.4%), loud snoring (20.5%), daytime tiredness (22.2%) and slow-walking pace (26.9%). The 95% CI risk differences (multivariable-adjusted) for slow vs. faster walking pace were; sleep apnoea (0.4-2.5%), self-reported apnoeas (0.1-3.8%), loud snoring (1.2-8.3%), and daytime tiredness (3.0-7.8%). Risk differences were similar between sexes. The multivariable-adjusted risk ratio indicated that slower walkers had 1.5 (95% CI: 1.0 to 2.1) times the risk of sleep apnoea vs. faster walkers. In conclusion, a slower walking speed was associated with a greater prevalence of sleep-disordered breathing, independently from other common screening factors. Therefore, a simple walking speed question may help consolidate screening for this disorder.