Change in commute mode and BMI: longitudinal, prospective evidence from UK Biobank

BACKGROUND: Insufficient physical activity is a determinant of obesity and cardiovascular disease. Active travel to work has declined in high-income countries in recent decades. We aimed to determine which socioeconomic and demographic characteristics predicted switching to or from active commuting, whether switching from passive to active commuting (or the reverse) independently predicts change in objectively measured body-mass index (BMI), and to ascertain whether any association is attenuated by socioeconomic, demographic, or behavioural factors. METHODS: This study used longitudinal data from UK Biobank. Baseline data collection occurred at 22 centres between March, 2006, and July, 2010, with a repeat assessment at one centre (Stockport) between August, 2012, and June, 2013, for a subset of these participants. Height and weight were objectively measured at both timepoints. We included individuals present at both timepoints with complete data in the analytic sample. Participants were aged 40–69 years and commuted from home to a workplace on a regular basis at both baseline and follow-up. Two exposures were investigated: transition from car commuting to active or public transport commuting and transition from active or public transport to car commuting. Change in BMI between baseline and repeat assessment was the outcome of interest, assessed with bivariate and multivariate logistic regression models. FINDINGS: 502 656 individuals provided baseline data, with 20 346 participating in the repeat assessment after a median of 4·4 years (IQR 3·7–4·9). 5861 individuals were present at both timepoints and had complete data for all analytic variables. Individuals who transitioned from car commuting at baseline to active or public transportation modes at follow-up had a decrease in BMI of −0·30 kg/m2 (95% CI −0·47 to −0·13; p=0·0005). Conversely, individuals who transitioned from active commuting at baseline to car commuting at follow-up had a BMI increase of 0·32 kg/m2 (0·13 to 0·50; p=0·008). These effects were not attenuated by adjustment for hypothesised confounders. Change in household income emerged as a determinant of commute mode transitions. INTERPRETATION: Incorporation of increased levels of physical activity as part of the commute to work could reduce obesity among middle-aged adults in the UK. FUNDING: UK Medical Research Council

How effective is the Forestry Commission Scotland's woodland improvement programme--'Woods In and Around Towns' (WIAT)--at improving psychological well-being in deprived urban communities? A quasi-experimental study

Introduction: There is a growing body of evidence that suggests that green spaces may positively influence psychological well-being. This project is designed to take advantage of a natural experiment where planned physical and social interventions to enhance access to natural environments in deprived communities provide an opportunity to prospectively assess impacts on perceived stress and mental well-being.<p></p> Study design and methods: A controlled, prospective study comprising a repeat cross-sectional survey of residents living within 1.5 km of intervention and comparison sites. Three waves of data will be collected: prephysical environment intervention (2013); postphysical environment intervention (2014) and postwoodland promotion social intervention (2015). The primary outcome will be a measure of perceived stress (Perceived Stress Scale) preintervention and postintervention. Secondary, self-report outcomes include: mental well-being (Short Warwick-Edinburgh Mental Well-being Scale), changes in physical activity (IPAQ-short form), health (EuroQoL EQ-5D), perception and use of the woodlands, connectedness to nature (Inclusion of Nature in Self Scale), social cohesion and social capital. An environmental audit will complement the study by evaluating the physical changes in the environment over time and recording any other contextual changes over time. A process evaluation will assess the implementation of the programme. A health economics analysis will assess the cost consequences of each stage of the intervention in relation to the primary and secondary outcomes of the study.<p></p> Ethics and dissemination: Ethical approval has been given by the University of Edinburgh, Edinburgh College of Art Research, Ethics and Knowledge Exchange Committee (ref. 19/06/2012). Findings will be disseminated through peer-reviewed publications, national and international conferences and, at the final stage of the project, through a workshop for those interested in implementing environmental interventions.<p></p&gt

Dynamics of silver elution from functionalised antimicrobial nanofiltration membranes

In an effort to mitigate biofouling on thin film composite membranes such as nanofiltration and reverse osmosis, a myriad of different surface modification strategies has been published. The use of silver nanoparticles (Ag-NPs) has emerged as being particularly promising. Nevertheless, the stability of these surface modifications is still poorly understood, particularly under permeate flux conditions. Leaching or elution of Ag-NPs from the membrane surface can not only affect the antimicrobial characteristics of the membrane, but could also potentially present an environmental liability when applied in industrial-scale systems. This study sought to investigate the dynamics of silver elution and the bactericidal effect of an Ag-NP functionalised NF270 membrane. Inductively coupled plasma-atomic emission spectroscopy was used to show that the bulk of leached silver occurred at the start of experimental runs, and was found to be independent of salt or permeate conditions used. Cumulative amounts of leached silver did, however, stabilise following the initial release, and were shown to have maintained the biocidal characteristics of the modified membrane, as observed by a higher fraction of structurally damaged Pseudomonas fluorescens cells. These results highlight the need to comprehensively assess the time-dependent nature of bactericidal membranes

Upper crustal structures beneath Yogyakarta imaged by ambient seismic noise tomography

Delineating the upper crustal structures beneath Yogyakarta is necessary for understanding its tectonic setting. The presence of Mt. Merapi, fault line and the alluvial deposits contributes to the complex geology of Yogyakarta. Recently, ambient seismic noise tomography can be used to image the subsurface structure. The cross correlations of ambient seismic noise of pair stations were applied to extract the Green's function. The total of 27 stations from 134 seismic stations available in MERapi Amphibious EXperiment (MERAMEX) covering Yogyakarta region were selected to conduct cross correlation. More than 500 Rayleigh waves of Green's functions could be extracted by cross-correlating available the station pairs of short-period and broad-band seismometers. The group velocities were obtained by filtering the extracted Green's function between 0.5 and 20 s. 2-D inversion was applied to the retrieved travel times. Features in the derived tomographic images correlate with the surface geology of Yogyakarta. The Merapi active volcanoes and alluvial deposit in Yogyakarta are clearly described by lower group velocities. The high velocity anomaly contrasts which are visible in the images obtained from the period range between 1 and 5 s, correspond to subsurface imprints of fault that could be the Opak Fault.The authors gratefully acknowledge the Graduate Research on Earthquake and Active Tectonics that supported this research through a Project of ActiveFault Research and Education for Earthquake Hazard Assessment in Indonesia, AUSAID agreement 58029

Hedgehog Pathway Activation Alters Ciliary Signaling in Primary Hypothalamic Cultures

Primary cilia dysfunction has been associated with hyperphagia and obesity in both ciliopathy patients and mouse models of cilia perturbation. Neurons throughout the brain possess these solitary cellular appendages, including in the feeding centers of the hypothalamus. Several cell biology questions associated with primary neuronal cilia signaling are challenging to address in vivo. Here we utilize primary hypothalamic neuronal cultures to study ciliary signaling in relevant cell types. Importantly, these cultures contain neuronal populations critical for appetite and satiety such as pro-opiomelanocortin (POMC) and agouti related peptide (AgRP) expressing neurons and are thus useful for studying signaling involved in feeding behavior. Correspondingly, these cultured neurons also display electrophysiological activity and respond to both local and peripheral signals that act on the hypothalamus to influence feeding behaviors, such as leptin and melanin concentrating hormone (MCH). Interestingly, we found that cilia mediated hedgehog signaling, generally associated with developmental processes, can influence ciliary GPCR signaling (Mchr1) in terminally differentiated neurons. Specifically, pharmacological activation of the hedgehog-signaling pathway using the smoothened agonist, SAG, attenuated the ability of neurons to respond to ligands (MCH) of ciliary GPCRs. Understanding how the hedgehog pathway influences cilia GPCR signaling in terminally differentiated neurons could reveal the molecular mechanisms associated with clinical features of ciliopathies, such as hyperphagia-associated obesity

The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus : a systematic review and economic evaluation

Background The two main types of diabetes are type 1 (formerly called insulin-dependent diabetes) and type 2 (formerly called non-insulin-dependent diabetes). In type 1, insulin is always required because the insulin-producing islet cells in the pancreas have been destroyed. In type 2, the pancreas can still produce insulin, and treatment is initially with diet and exercise, but the disease often progresses, with deteriorating control and rising blood glucose levels, and a need next for oral hypoglycaemic agents (OHAs), and later for insulin in about 30%. The aim of insulin therapy is to reduce blood glucose to normal levels, without going too low and causing hypoglycaemia. Insulin currently has to be given by injection. There are various types according to duration of action – short, intermediate and long. Short- and long-acting insulin both come in two forms: traditional and the newer analogues. The traditional form of short-acting insulin is known as soluble. It is given by injection using an insulin pen, or a syringe and needle. Insulin can also be given by continuous subcutaneous infusion by an insulin pump, usually only in selected patients with type 1 diabetes. Objective The aim was to review the clinical effectiveness and cost-effectiveness of a new technology, the inhaled insulin, Exubera® (Pfizer and Sanofi-Aventis in collaboration with Nektar Technologies), a short-acting insulin. Methods A systematic literature review was conducted and economic modelling carried out. Literature searches were done up to November 2005. The industry model, EAGLE, was used for modelling. Results Clinical effectiveness Nine trials of inhaled insulins were found, but only seven used the Exubera form of inhaled insulin. The other two used inhaled insulins that have not yet been licensed. There were five trials in type 1 and two in type 2 diabetes. Inhaled insulin is clinically effective, and is as good as short-acting soluble insulin in controlling blood glucose. The frequency of hypoglycaemia is similar. It works slightly more quickly than soluble insulin. None of the published trials compared it with short-acting analogues, which would have provided a better comparison since they also work slightly more rapidly than soluble. There is also a problem in most of the trials in that patients were on combinations of short-acting, and either long- or intermediate-acting insulin, and both were changed, making it more difficult to assess the effects of only the change from soluble to inhaled insulin. The only significant difference between inhaled and soluble insulin in the trials was in patient preference. Most patients preferred inhaled to injected short-acting insulin, and this has some effect on quality of life measures. However, there could be some bias operating in the trials. The control groups mostly used syringes and needles, rather than pens. As pens are more convenient, their use might have narrowed the patient satisfaction difference. The manufacturer, Pfizer, argues that this patient preference could lead to improved control in some type 1 patients, through improved compliance with treatment, and in some type 2 patients poorly controlled on oral agents, because a switch to insulin therapy would be more acceptable if people could use inhaled rather than injected insulin. These assertions are unproven. There were no trials of inhaled insulin against continuous subcutaneous insulin infusion (CSII). Safety Concern has been raised about the long-term effects of inhaled insulin in the lung. So far, no serious adverse effects have been seen, but until many thousands of people have used inhaled insulin for many years, one cannot rule out some uncommon or rare, but serious, adverse effects. Cost-effectiveness The manufacturer's model (EAGLE) appears to be a high-quality one. However, the results depend more on the assumptions fed into the model than on the model itself. The key assumptions are the size of the gain in quality of life utility from inhaling rather than injecting insulin, the effect of having an inhaled option on the willingness to start insulin among people with poor diabetic control on oral drugs, and the effect on glycaemic control. We consider that the assumptions used in the industry submission make the cost-effectiveness appear better than it really would be. The manufacturer's submission assumed utility gains of 0.036–0.075 in patients with type 1 diabetes, and 0.027–0.067 in those with type 2, based on an unpublished utility elicitation study sponsored by the manufacturer. We thought that these gains were optimistic and that gains of 0.02 or less were more likely, on average. However, patients with particular problems with injection sites might have more to gain, although they might also be a group with much to gain from CSII. A key factor is the cost of inhaled insulin. Much more insulin has to be given by inhaler than by injection, and so the cost of inhaled insulin is much higher than injected. The extra cost depends on dosage, but ranges from around £600 to over £1000 per patient per year. Conclusion The inhaled insulin, Exubera, appears to be effective and safe, but the cost is so much more that it is unlikely to be cost-effective

A one-phase interior point method for nonconvex optimization

The work of Wachter and Biegler suggests that infeasible-start interior point methods (IPMs) developed for linear programming cannot be adapted to nonlinear optimization without significant modification, i.e., using a two-phase or penalty method. We propose an IPM that, by careful initialization and updates of the slack variables, is guaranteed to find a first-order certificate of local infeasibility, local optimality or unboundedness of the (shifted) feasible region. Our proposed algorithm differs from other IPM methods for nonconvex programming because we reduce primal feasibility at the same rate as the barrier parameter. This gives an algorithm with more robust convergence properties and closely resembles successful algorithms from linear programming. We implement the algorithm and compare with IPOPT on a subset of CUTEst problems. Our algorithm requires a similar median number of iterations, but fails on only 9% of the problems compared with 16% for IPOPT. Experiments on infeasible variants of the CUTEst problems indicate superior performance for detecting infeasibility. The code for our implementation can be found at https://github.com/ohinder/OnePhase .Comment: fixed typo in sign of dual multiplier in KKT syste

The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease : systematic review

Coronary heart disease (CHD) is one of the main causes of mortality and morbidity in the UK and other Western countries. The disease can be asymptomatic until the first event, which may be a fatal myocardial infarction (heart attack). Half of all heart attacks occur in people who have had no prior warning of coronary disease, and almost half will die from the first attack. Risk scores based on well-known factors such as age, blood pressure, smoking, cholesterol and diabetes have been used to assess risk, but are imperfect: not all high-risk people develop heart disease, and many low-risk people do. Indeed, depending on which cut-off is used to define high risk, most heart attacks occur in low-risk people, because the number of people at low risk is much greater than the number at high risk. There is therefore a need for a better way of identifying those at risk so that they can treat themselves with lifestyle measures, or receive drug therapy such as statins and antihypertensive drugs as appropriate. Computed tomography (CT) is a form of radiological imaging that can detect calcium deposits in the coronary arteries. This calcification is a marker for CHD, and so CT imaging could be a way of detecting asymptomatic but serious CHD. CT is quick and non-invasive, but does involve a relatively large radiation dose

National Evaluation of the Healthy Communities Challenge Fund: The Healthy Towns Programme in England

Background and aims     This research reported here presents findings from an evaluation of the development and implementation of the Healthy Community Challenge Fund (otherwise known as the ‘Healthy Towns’ programme). A key aim of the research has been to inform the development of future environmental and systems‐based ‘whole town’ approaches to obesity prevention. The overall aim of the Healthy Towns programme was to pilot and stimulate novel ‘whole town’ approaches that tackle the ‘obesogenic’ environment in order to reduce obesity, with a particular focus on improving diet and increasing physical activity. Through a competitive tender process, nine towns were selected that represented urban areas across England ranging from small market towns to areas of large cities. The fund provided £30 million over the period 2008‐2011, divided amongst the nine towns. The amounts awarded ranged from £900,000 to £4.85 million. Towns were instructed to be innovative and were given freedom to develop a locally‐specific programme of interventions. This report supplements local process and impact evaluations undertaken by each town (not reported here) by taking an overall view of the programme’s development and implementation. Our evaluation therefore addressed the following research questions: 1. What kinds of interventions were delivered across the Healthy Towns programme? 2. Were environmental and infrastructural interventions equitably delivered? 3. How was the Healthy Towns programme theorised and translated into practice? 4. How was evidence used in the selection and design of interventions? 5. What are the barriers and facilitators to the implementation of a systems approach to obesity prevention