Multivariate QST-FST comparisons: a neutrality test for the evolution of the g matrix in structured populations.

Neutrality tests in quantitative genetics provide a statistical framework for the detection of selection on polygenic traits in wild populations. However, the existing method based on comparisons of divergence at neutral markers and quantitative traits (Q(st)-F(st)) suffers from several limitations that hinder a clear interpretation of the results with typical empirical designs. In this article, we propose a multivariate extension of this neutrality test based on empirical estimates of the among-populations (D) and within-populations (G) covariance matrices by MANOVA. A simple pattern is expected under neutrality: D = 2F(st)/(1 - F(st))G, so that neutrality implies both proportionality of the two matrices and a specific value of the proportionality coefficient. This pattern is tested using Flury's framework for matrix comparison [common principal-component (CPC) analysis], a well-known tool in G matrix evolution studies. We show the importance of using a Bartlett adjustment of the test for the small sample sizes typically found in empirical studies. We propose a dual test: (i) that the proportionality coefficient is not different from its neutral expectation [2F(st)/(1 - F(st))] and (ii) that the MANOVA estimates of mean square matrices between and among populations are proportional. These two tests combined provide a more stringent test for neutrality than the classic Q(st)-F(st) comparison and avoid several statistical problems. Extensive simulations of realistic empirical designs suggest that these tests correctly detect the expected pattern under neutrality and have enough power to efficiently detect mild to strong selection (homogeneous, heterogeneous, or mixed) when it is occurring on a set of traits. This method also provides a rigorous and quantitative framework for disentangling the effects of different selection regimes and of drift on the evolution of the G matrix. We discuss practical requirements for the proper application of our test in empirical studies and potential extensions.

Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation.

BACKGROUND: Chronic lung allograft dysfunction, which manifests as bronchiolitis obliterans syndrome (BOS), is recognized as the primary cause of morbidity and mortality after lung transplantation. In this study we assessed the efficacy and safety of two de novo immunosuppression protocols to prevent BOS. METHODS: Our study approach was a multicenter, prospective, randomized (1:1) open-label superiority investigation of de novo tacrolimus vs cyclosporine, with both study arms given mycophenolate mofetil and prednisolone after lung transplantation. Cytolytic induction therapy was not employed. Patients were stratified at entry for cystic fibrosis. Primary outcome was incidence of BOS 3 years after transplant (intention-to-treat analysis). Secondary outcomes were survival and incidence of acute rejection, infection and other adverse events. RESULTS: Group demographic data were well matched: 110 of 124 tacrolimus vs 74 of 125 cyclosporine patients were treated per protocol (p < 0.01 by chi-square test). Cumulative incidence of BOS Grade ≥1 at 3 years was 11.6% (tacrolimus) vs 21.3% (cyclosporine) (cumulative incidence curves, p = 0.037 by Gray's test, pooled over strata). Univariate proportional sub-distribution hazards regression confirmed cyclosporine as a risk for BOS (HR 1.97, 95% CI 1.04 to 3.77, p = 0.039). Three-year cumulative incidence of acute rejection was 67.4% (tacrolimus) vs 74.9% (cyclosporine) (p = 0.118 by Gray's test). One- and 3-year survival rates were 84.6% and 78.7% (tacrolimus) vs 88.6% and 82.8% (cyclosporine) (p = 0.382 by log-rank test). Cumulative infection rates were similar (p = 0.91), but there was a trend toward new-onset renal failure with tacrolimus (p = 0.09). CONCLUSIONS: Compared with cyclosporine, de novo tacrolimus use was found to be associated with a significantly reduced risk for BOS Grade ≥1 at 3 years despite a similar rate of acute rejection. However, no survival advantage was detected.

Well-differentiated papillary mesothelioma of the tunica vaginalis testis: imaging on Tc-99m heat-denatured red blood cell scintigraphy.

An 18-year-old man presented with a growing painless left scrotal mass. Sonography showed a hydrocele and a homogeneous, well-encapsulated left extratesticular mass with similar echogenicity as the normal testis, suggestive of a splenogonadal fusion. To substantiate the diagnosis, the patient underwent Tc-99m heat-denatured red blood cell scintigraphy showing normal physiological hyperactivity in the spleen but activity similar to the blood pool projecting on the upper part of the left testis. This made testicular splenic tissue less likely. The patient underwent resection and histopathology revealed a well-differentiated papillary mesothelioma. Inguinal orchidectomy was subsequently performed and the patient was free of recurrence at 18 months.

Managing health and increasing well-being

The Building the Community-Pharmacy Partnership has worked to improve local health outcomes by encouraging members of the community to develop skills relating to managing their own health, and providing accessible information on the availability of services of which they can avail of. The aim is to facilitate local people to gain knowledge on various health issues through books, videos, leaflets and enable the most vulnerable and in need to access additional support through the pharmacy to complementary therapy. Outcome: A room in the pharmacy has been renovated and offers access to other support services. Funding has allowed the pharmacist to equip the room with videos, leaflets, books etc. There has been an increase in partnership working between the community group, pharmacist and more contact has been made with primary care. Further funding has allowed for the development of a subsidised support referral service for counselling and complementary therapies. As well as this, the pharmacist has worked with local groups to provide information sessions on lifestyle and on health issues identified by the local groups

Eat well, keep well and reduce your risk of cancer

This leaflet highlights Northern Ireland's incidence of cancer as an important public health concern, and explains how eating more fruit, vegetables and other fibre rich foods can significantly reduce our risk of getting the disease.

Survey of Lifestyle, Attitudes and Nutrition in Ireland. Mental Health and Social Well-being Report

SĹN 2007: Older People, Loneliness and Social Support to Mental HealthSĹN, the national Survey of Lifestyle, Attitudes and Nutrition, shows that most Irish adults have a reasonably high level of positive mental health. It is the largest national survey on positive and negative mental health and social well-being in the Irish adult population.��One finding highlights the significance of loneliness and social support to mental health. Finding reveal that 14% of respondents reported being often lonely in the last four weeks, with women, older people and respondents in lower social class groups reporting high levels of loneliness. The SĹN report indicates that being widowed and not being in paid employment are the strongest overall predictors of loneliness. Respondents who are widowed are about five times more likely to feel lonely than those who are married or cohabiting, while 17% of respondents aged 65 and over report being often lonely.��SLAN 2007 highlights the significance of loneliness and social support to mental health. It proposes community-based interventions, including community development approaches and strategies to promote community involvement as a way to tackle such social and health inequities at local level. The report also highlights the importance of implementing the recommendations of the policy document A Vision for Change. It says that protection and promotion of the future health and well-being of the Irish population requires the implementation of effective cross-sectoral policies that will help create and maintain a mentally healthy society, with consequent health, economic and social benefits for all.����SLAN is commissioned by the Department of Health and Children and involved face-to-face interviews with 10,364 respondents aged 18 years and over.��

Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach.

Although the relationship between serum uric acid (SUA) and adiposity is well established, the direction of the causality is still unclear in the presence of conflicting evidences. We used a bidirectional Mendelian randomization approach to explore the nature and direction of causality between SUA and adiposity in a population-based study of Caucasians aged 35 to 75 years. We used, as instrumental variables, rs6855911 within the SUA gene SLC2A9 in one direction, and combinations of SNPs within the adiposity genes FTO, MC4R and TMEM18 in the other direction. Adiposity markers included weight, body mass index, waist circumference and fat mass. We applied a two-stage least squares regression: a regression of SUA/adiposity markers on our instruments in the first stage and a regression of the response of interest on the fitted values from the first stage regression in the second stage. SUA explained by the SLC2A9 instrument was not associated to fat mass (regression coefficient [95% confidence interval]: 0.05 [-0.10, 0.19] for fat mass) contrasting with the ordinary least square estimate (0.37 [0.34, 0.40]). By contrast, fat mass explained by genetic variants of the FTO, MC4R and TMEM18 genes was positively and significantly associated to SUA (0.31 [0.01, 0.62]), similar to the ordinary least square estimate (0.27 [0.25, 0.29]). Results were similar for the other adiposity markers. Using a bidirectional Mendelian randomization approach in adult Caucasians, our findings suggest that elevated SUA is a consequence rather than a cause of adiposity.

Guide for World Class Commissioners Promoting Health and Well-being: Reducing Inequalities

One of the core missions of commissioners is to reduce health inequalities. Promoting health and well-being is necessary but not sufficient, and it is essential thatimprovements in commissioning and consequent improvements in service delivery, will not widen the gapbetween different groups in society. It is, of course,already difficult enough to decide how to commission services to promote health and well-being. There are practical, economic and ethical issues involved, but if in addition the commissioner wishes to ensure that the gap between the most healthy and the least healthy does not widen, they will have to think hard and commission carefully. It is also crystal clear that it would be wrong to let 152 Primary Care Trusts find out for themselves how to do this. Firstly, it would be a massive waste of resources, and secondly, many Primary Care Trusts would be unable to deliver. This Guide has been produced by knowledge harvesting; by gathering the knowledge that commissioners have created and accrued, about successes as well as failures; and blending it into a single readable Guide.

The Health and Well-Being of Children and Young People in South East England 2005 (report)

A compendium of facts and figures on the health status and the determinants of the health of children and young people in South East England

Commissioning framework for health and well-being

This framework builds on the White Paper Our health, our care, our say, which promised to help people stay healthy and independent, to give people choice in their care services, to deliver services closer to home and to tackle inequalities. The Commissioning framework for health and well-being sets out the eight steps that health and social care should take in partnership to commission more effectively. It is aimed at commissioners and providers of services in health, social care and local authorities. It is part of the White Paper Our health our care our say implementation.

Eat well, keep well and reduce your risk of cancer

What we eat affects our health. With just a few small changes to what we eat every day, we can help to protect against major illnesses, including some cancers. These changes can also give our health an extra boost.

Eat well plate

This poster shows graphically how much of each of the following food groups we should eat for a healthy, balanced diet: fruit and vegetables; bread, rice, potatoes, pasta and other starchy foods; milk and dairy foods; meat, fish, eggs, beans and other non-dairy sources of protein; and foods and drinks high in fat and/or sugar.��

Are light traps baited with kairomones effective in the capture of Lutzomyia longipalpis and Lutzomyia intermedia? An evaluation of synthetic human odor as an attractant for phlebotomine sand flies (Diptera: Psychodidae: Phlebotominae)

Phlebotomine sand flies are often captured with human bait and/or light traps, either with or without an animal bait. More recently, synthetic attractants have been used as bait in traps to improve the capture of phlebotomine sand flies as well as other insects of medical and veterinary importance. The aim of the present study was to evaluate the effects of the kairomone 1-octen-3-ol (octenol) and the synthetic human odor BG-Mesh LureTM (BGML - lactic acid, caproic acid and ammonia) baited in modified CDC light traps on the capture of phlebotomine sand flies. The experiments followed the 5x5 Latin square design. Among the species caught, Lutzomyia intermedia apparently presented a dose-dependent response to octenol. The response obtained with the BGML, alone or in combination with octenol (5 mg/h), indicated some degree of attractiveness of these baits to different phlebotomine sand fly species. Octenol seems to be more attractive to L. intermedia than to Lutzomyia longipalpis, while the BGML presented a higher success in capturing L. longipalpis. When the components of the BGML were used separately, there was no increase in catching the female of L. intermedia. Apparently, there was no synergistic effect between the octenol and the BGML. In conclusion, the octenol and the BGML were demonstrated to be possible baits to attract some phlebotomine sand fly species.

Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins.

The polymeric Ig receptor (pIgR) ensures efficient secretion of polymeric IgA (pIgA) at mucosal surfaces. On basal to apical transport across epithelial cells, the pIgR extracellular domain is cleaved, releasing secretory component (SC) in association with pIgA. This finds its raison d'être in the recent observation that SC is directly involved in the protective function of secretory IgA. In addition, free SC exhibits scavenger properties with respect to enteric pathogens. However, although pIgR dedicates its life to mucosal protection, it also seems to permit pathogen entrance through the epithelial barrier. The multiple mechanisms that they are involved in make pIgR and SC instrumental to mucosal immunity.