Systematic reviews of and integrated report on the quantitative, qualitative and economic evidence base for the management of obesity in men

<b>Background</b><p></p> Obesity increases the risk of many serious illnesses such as coronary heart disease, type 2 diabetes and osteoarthritis. More men than women are overweight or obese in the UK but men are less likely to perceive their weight as a problem and less likely to engage with weight-loss services.<p></p> <b>Objective</b><p></p> The aim of this study was to systematically review evidence-based management strategies for treating obesity in men and investigate how to engage men in obesity services by integrating the quantitative, qualitative and health economic evidence base.<p></p> <b>Data sources</b><p></p> Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects and the NHS Economic Evaluation Database were searched from inception to January 2012, with a limited update search in July 2012. Subject-specific websites, reference lists and professional health-care and commercial organisations were also consulted.<p></p> <b>Review methods</b><p></p> Six systematic reviews were conducted to consider the clinical effectiveness, cost-effectiveness and qualitative evidence on interventions for treating obesity in men, and men in contrast to women, and the effectiveness of interventions to engage men in their weight reduction. Randomised controlled trials (RCTs) with follow-up data of at least 1 year, or any study design and length of follow-up for UK studies, were included. Qualitative and mixed-method studies linked to RCTs and non-randomised intervention studies, and UK-based, men-only qualitative studies not linked to interventions were included. One reviewer extracted data from the included studies and a second reviewer checked data for omissions or inaccuracies. Two reviewers carried out quality assessment. We undertook meta-analysis of quantitative data and a realist approach to integrating the qualitative and quantitative evidence synthesis.<p></p> <b>Results</b><p></p> From a total of 12,764 titles reviewed, 33 RCTs with 12 linked reports, 24 non-randomised reports, five economic evaluations with two linked reports, and 22 qualitative studies were included. Men were more likely than women to benefit if physical activity was part of a weight-loss programme. Reducing diets tended to produce more favourable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise programme -3.2 kg, 95% CI -4.8 kg to -1.6 kg). The type of reducing diet did not affect long-term weight loss. A reducing diet plus physical activity and behaviour change gave the most effective results. Low-fat reducing diets, some with meal replacements, combined with physical activity and behaviour change training gave the most effective long-term weight change in men [-5.2 kg (standard error 0.2 kg) after 4 years]. Such trials may prevent type 2 diabetes in men and improve erectile dysfunction. Although fewer men joined weight-loss programmes, once recruited they were less likely to drop out than women (difference 11%, 95% CI 8% to 14%). The perception of having a health problem (e.g. being defined as obese by a health professional), the impact of weight loss on health problems and desire to improve personal appearance without looking too thin were motivators for weight loss amongst men. The key components differ from those found for women, with men preferring more factual information on how to lose weight and more emphasis on physical activity programmes. Interventions delivered in social settings were preferred to those delivered in health-care settings. Group-based programmes showed benefits by facilitating support for men with similar health problems, and some individual tailoring of advice assisted weight loss in some studies. Generally, men preferred interventions that were individualised, fact-based and flexible, which used business-like language and which included simple to understand information. Preferences for men-only versus mixed-sex weight-loss group programmes were divided. In terms of context, programmes which were cited in a sporting context where participants have a strong sense of affiliation showed low drop out rates and high satisfaction. Although some men preferred weight-loss programmes delivered in an NHS context, the evidence comparing NHS and commercial programmes for men was unclear. The effect of family and friends on participants in weight-loss programmes was inconsistent in the evidence reviewed - benefits were shown in some cases, but the social role of food in maintaining relationships may also act as a barrier to weight loss. Evidence on the economics of managing obesity in men was limited and heterogeneous.<p></p> <b>Limitations</b><p></p> The main limitations were the limited quantity and quality of the evidence base and narrow outcome reporting, particularly for men from disadvantaged and minority groups. Few of the studies were undertaken in the UK.<p></p> <b>Conclusions</b><p></p> Weight reduction for men is best achieved and maintained with the combination of a reducing diet, physical activity advice or a physical activity programme, and behaviour change techniques. Tailoring interventions and settings for men may enhance effectiveness, though further research is needed to better understand the influence of context and content. Future studies should include cost-effectiveness analyses in the UK setting

Introducing a designing attitude in dementia care

This paper discusses how design can enhance the wellbeing of people living with dementia, their carers and caregivers. It refers to two examples of recent design research that focus on supporting the provision and facilitation of appropriate activities and environments for individuals with advanced dementia in residential care. The projects use interdisciplinary co-design approaches and ethnographic methods to establish new knowledge and develop user-centred design solutions to improve care. Questioning how to REDO design research to create a sustainable impact on the lives of those affected by dementia, the paper concludes that active involvement and continued participation of users, carers and care practitioners in the design process is essential. Training on design skills and making will enable carers to adapt a designing attitude. Exploring how such training can be delivered is a chance for the design community, in collaboration with experts from health care, to take the lead in solving this problem

Chandra Detection of a TypeII Quasar at z=3.288

We report on observations of a TypeII quasar at redshift z=3.288, identified as a hard X-ray source in a 185 ks observation with the Chandra X-ray Observatory and as a high-redshift photometric candidate from deep, multiband optical imaging. CXOJ084837.9+445352 (hereinafter CXO52) shows an unusually hard X-ray spectrum from which we infer an absorbing column density N(H) = (4.8+/-2.1)e23 / cm2 (90% confidence) and an implied unabsorbed 2-10 keV rest-frame luminosity of L(2-10) = 3.3e44 ergs/s, well within the quasar regime. Hubble Space Telescope imaging shows CXO52 to be elongated with slight morphological differences between the WFPC2 F814W and NICMOS F160W bands. Optical and near-infrared spectroscopy of CXO52 show high-ionization emission lines with velocity widths ~1000 km/s and flux ratios similar to a Seyfert2 galaxy or radio galaxy. The latter are the only class of high-redshift TypeII luminous AGN which have been extensively studied to date. Unlike radio galaxies, however, CXO52 is radio quiet, remaining undetected at radio wavelengths to fairly deep limits, f(4.8GHz) < 40 microJy. High-redshift TypeII quasars, expected from unification models of active galaxies and long-thought necessary to explain the X-ray background, are poorly constrained observationally with few such systems known. We discuss recent observations of similar TypeII quasars and detail search techniques for such systems: namely (1) X-ray selection, (2) radio selection, (3) multi-color imaging selection, and (4) narrow-band imaging selection. Such studies are likely to begin identifying luminous, high-redshift TypeII systems in large numbers. We discuss the prospects for these studies and their implications to our understanding of the X-ray background.Comment: 28 pages, 5 figures; to appear in The Astrophysical Journa

Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results

The identification of microbiological infection is usually a diagnostic investigation, a complex process that is firstly initiated by clinical suspicion. With the emergence of high-throughput sequencing (HTS) technologies, metagenomic analysis has unveiled the power to identify microbial DNA/RNA from a diverse range of clinical samples (1). Metagenomic analysis of whole human genomes at the clinical/research interface bypasses the steps of clinical scrutiny and targeted testing and has the potential to generate unexpected findings relating to infectious and sometimes transmissible disease. There is no doubt that microbial findings that may have a significant impact on a patient’s treatment and their close contacts should be reported to those with clinical responsibility for the sample-donating patient. There are no clear recommendations on how such findings that are incidental, or outside the original investigation, should be handled. Here we aim to provide an informed protocol for the management of incidental microbial findings as part of the 100,000 Genomes Projectwhich may have broader application in this emerging field. As with any other clinical information, we aim to prioritise the reporting of data that are most likely to be of benefit to the patient and their close contacts. We also set out to minimize risks, costs and potential anxiety associated with the reporting of results that are unlikely to be of clinical significance. Our recommendations aim to support the practice of microbial metagenomics by providing a simplified pathway that can be applied to reporting the identification of potential pathogens from metagenomic datasets. Given that the ambition for UK sequenced human genomes over the next 5 years has been set to reach 5 million and the field of metagenomics is rapidly evolving, the guidance will be regularly reviewed and will likely adapt over time as experience develops

Pacific Ocean inflow : influence on catastrophic reduction of sea ice cover in the Arctic Ocean

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 33 (2006): L08605, doi:10.1029/2005GL025624.The spatial pattern of recent ice reduction in the Arctic Ocean is similar to the distribution of warm Pacific Summer Water (PSW) that interflows the upper portion of halocline in the southern Canada Basin. Increases in PSW temperature in the basin are also well-correlated with the onset of sea-ice reduction that began in the late 1990s. However, increases in PSW temperature in the basin do not correlate with the temperature of upstream source water in the northeastern Bering Sea, suggesting that there is another mechanism which controls these concurrent changes in ice cover and upper ocean temperature. We propose a feedback mechanism whereby the delayed sea-ice formation in early winter, which began in 1997/1998, reduced internal ice stresses and thus allowed a more efficient coupling of anticyclonic wind forcing to the upper ocean. This, in turn, increased the flux of warm PSW into the basin and caused the catastrophic changes.This work was funded in part by Japan Agency for Marine-Earth Science and Technology, Fisheries and Oceans Canada, and the U.S. National Science Foundation

Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies.

The evolution of sexual dimorphism is constrained by a shared genome, leading to 'sexual antagonism', in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation

Mental health consumer and caregiver perceptions of stigma in Australian community pharmacies

Background: The stigma of mental illness can be a barrier to effective medication management in the community pharmacy setting. This article explored mental health consumers’ or caregivers’ experiences of stigma in Australian community pharmacies. Materials: Semi-structured interviews and focus groups were conducted with a purposive sample of consumers or caregivers (n = 74). Interview transcripts were analysed using a general inductive approach. Discussion: Stigma presented a barrier to effective mental health management. Self-stigma impeded consumers’ community pharmacy engagement. Positive relationships with knowledgeable staff are fundamental to reducing stigma. Conclusions: Findings provide insight into the stigma of mental illness in community pharmacies

Structural insights into the MMACHC-MMADHC protein complex involved in vitamin B12 trafficking

Conversion of vitamin B12 (cobalamin, Cbl) into the cofactor forms methyl-Cbl (MeCbl) and adenosyl-Cbl (AdoCbl) is required for the function of two crucial enzymes, mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase, respectively. The intracellular proteins MMACHC and MMADHC play important roles in processing and targeting the Cbl cofactor to its destination enzymes, and recent evidence suggests that they may interact while performing these essential trafficking functions. To better understand the molecular basis of this interaction, we have mapped the crucial protein regions required, indicate that Cbl is likely processed by MMACHC prior to interaction with MMADHC, and identify patient mutations on both proteins that interfere with complex formation, via different mechanisms. We further report the crystal structure of the MMADHC C-terminal region at 2.2 Å resolution, revealing a modified nitroreductase fold with surprising homology to MMACHC despite their poor sequence conservation. Because MMADHC demonstrates no known enzymatic activity, we propose it as the first protein known to repurpose the nitroreductase fold solely for protein-protein interaction. Using small angle x-ray scattering, we reveal the MMACHC-MMADHC complex as a 1:1 heterodimer and provide a structural model of this interaction, where the interaction region overlaps with the MMACHC-Cbl binding site. Together, our findings provide novel structural evidence and mechanistic insight into an essential biological process, whereby an intracellular "trafficking chaperone" highly specific for a trace element cofactor functions via protein-protein interaction, which is disrupted by inherited disease mutations