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BackgroundUp to 2% of suicides in young people may occur in clusters i.e., close together in time and space. In early 2008 unprecedented attention was given by national and international news media to a suspected suicide cluster among young people living in Bridgend, Wales. This paper investigates the strength of statistical evidence for this apparent cluster, its size, and temporal and geographical limits.Methods and findingsThe analysis is based on official mortality statistics for Wales for 2000-2009 provided by the UK's Office for National Statistics (ONS). Temporo-spatial analysis was performed using Space Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and over, with a sub-group analysis focussing on cases aged 15-34 years. These analyses were conducted for deaths coded by ONS as: (i) suicide or of undetermined intent (probable suicides) and (ii) for a combination of suicide, undetermined, and accidental poisoning and hanging (possible suicides). The temporo-spatial analysis did not identify any clusters of suicide or undetermined intent deaths (probable suicides). However, analysis of all deaths by suicide, undetermined intent, accidental poisoning and accidental hanging (possible suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths amongst 15-34 year olds centred on the County Borough of Bridgend for the period 27(th) December 2007 to 19(th) February 2008. Less than 1% of possible suicides in younger people in Wales in the ten year period were identified as being cluster-related.ConclusionsThere was a possible suicide cluster in young people in Bridgend between December 2007 and February 2008. This cluster was smaller, shorter in duration, and predominantly later than the phenomenon that was reported in national and international print media. Further investigation of factors leading to the onset and termination of this series of deaths, in particular the role of the media, is required.

In postmenopausal women, estrogen (E2) deficiencies are frequently associated with higher risk of intracranial hemorrhage, increased incidence of stroke, cerebral aneurysm, and decline in cognitive abilities. In younger postpartum women and those using oral contraceptives, perturbations in E2 are associated with higher risk of cerebral venous thrombosis. A number of serious intracranial pathologic conditions linked to E2 deficiencies, such as dural sinus thrombosis, dural fistulae, non-parenchymal intracranial hemorrhages, migraines, and spontaneous cerebrospinal fluid leaks, involve the vessels not of the brain itself, but of the outer fibrous membrane of the brain, the dura mater (DM). The pathogenesis of these disorders remains mysterious and how estrogen regulates structural and functional integrity of DM vasculature is largely unknown. Here, we demonstrate that post ovariectomy (OVX) DM vascular remodeling is manifested by microvessel destabilization, capillary rarefaction, increased vascular permeability, and aberrant angio-architecture, and is the result of disrupted E2-regulated PDGF-BB signaling within dura microvasculature. These changes, associated with the reduction in systemic PDGF-BB levels, are not corrected by a flat-dose E2 hormone replacement therapy (HRT), but are largely prevented using HRT schedules mimicking physiological E2 fluctuations. We demonstrate that 1) E2 regulates PDGF-BB production by endothelial cells in a dose-dependent manner and 2) optimization of PDGF-BB levels and induction of robust PDGF-mediated endothelial cell-vascular pericyte interactions require high (estrous) E2 concentrations. We conclude that high (estrous) levels of E2 are important in controlling PDGF-mediated crosstalk between endothelial cells and pericytes, a fundamental mechanism governing microvessel stability and essential for preserving intracranial homeostasis.

BACKGROUND: Fungus-cultivating termites make use of an obligate mutualism with fungi from the genus Termitomyces, which are acquired through either vertical transmission via reproductive alates or horizontally transmitted during the formation of new mounds. Termitomyces taxonomy, and thus estimating diversity and host specificity of these fungi, is challenging because fruiting bodies are rarely found. Molecular techniques can be applied but need not necessarily yield the same outcome than morphological identification. METHODOLOGY: Culture-dependent and culture-independent methods were used to comprehensively assess host specificity and gut fungal diversity. Termites were identified using mitochondrial cytochrome oxidase II (COII) genes. Twenty-three Termitomyces cultures were isolated from fungal combs. Internal transcribed spacer (ITS) clone libraries were constructed from termite guts. Presence of Termitomyces was confirmed using specific and universal primers. Termitomyces species boundaries were estimated by cross-comparison of macromorphological and sequence features, and ITS clustering parameters accordingly optimized. The overall trends in coverage of Termitomyces diversity and host associations were estimated using Genbank data. RESULTS AND CONCLUSION: Results indicate a monoculture of Termitomyces in the guts as well as the isolation sources (fungal combs). However, cases of more than one Termitomyces strains per mound were observed since mounds can contain different termite colonies. The newly found cultures, as well as the clustering analysis of GenBank data indicate that there are on average between one and two host genera per Termitomyces species. Saturation does not appear to have been reached, neither for the total number of known Termitomyces species nor for the number of Termitomyces species per host taxon, nor for the number of known hosts per Termitomyces species. Considering the rarity of Termitomyces fruiting bodies, it is suggested to base the future taxonomy of the group mainly on well-characterized and publicly accessible cultures.

Previous cross-sectional studies have suggested that biomarkers of extracellular matrix remodelling are associated with atrial fibrillation (AF), but no prospective data have yet been published. Hence, we examine whether plasma matrix metalloproteinases (MMP) and their inhibitors are related to increased risk of incident AF.We used a case-cohort design in the context of the prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible men and women free from AF in 1990-92, we selected a stratified random sample of 500 individuals without and 580 with incident AF over a mean follow-up of 11.8 years. Using a weighted proportional hazards regression model, the relationships between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were examined after adjusting for confounders.In models adjusted for age, sex and race, all biomarkers were associated with AF, but only the relationship between plasma MMP-9 remained significant in the fully-adjusted model: each one standard deviation increase in MMP-9 was associated with 27% (95% Confidence Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction with race or sex. Individuals with above mean levels of MMP-9 were more likely to be male, white and current smokers.The findings suggest that elevated levels of MMP-9 are independently associated with increased risk of AF. However, given the lack of specificity of MMP-9 to atrial tissue, it remains to be determined whether the observed relationship reflects the impact of atrial fibrosis or more generalized fibrosis on risk of incident AF.

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Disease prevention and control practices are frequently highlighted as important to ensure the health and welfare of farmed animals, although little is known as to why not many practices are carried out. The aim of this study was to identify the motivators and barriers of dairy cattle farmers towards the use of biosecurity measures on dairy farms using a health psychology approach. Twenty-five farmers on 24 farms in Great Britain (GB) were interviewed using the Theory of Planned Behaviour framework. Results indicated that farmers perceived they had the ability to control what happened on their farms in terms of preventing and controlling disease, and described benefits from being proactive and vigilant. However, barriers were cited in relation to testing inaccuracies, effectiveness and time-efficiency of practices, and disease transmission route (e.g., airborne transmission). Farmers reported they were positively influenced by veterinarians and negatively influenced by the government (Department for Environment Food & Rural Affairs (DEFRA)) and the general public. Decisions to implement practices were influenced by the perceived severity of the disease in question, if disease was diagnosed on the farm already, or was occurring on other farms. Farmers described undertaking a form of personal risk assessment when deciding if practices were worth doing, which did not always involve building in disease specific factors or opinions from veterinarians or other advisors. These results indicate that further guidance about the intricacies of control and prevention principles in relation to specific animal diseases may be required, with an obvious role for veterinarians. There appears to be an opportunity for farm advisors and herd health professionals to further understand farmer beliefs behind certain attitudes and target communication and advice accordingly to further enhance dairy cattle health and welfare.

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In Petron’s universe of 183 spheres forming a triangle, the spheres must rotate in alternate directions and their number must be even rather than odd.

Hellenistic evidence suggests for this site the toponym Dikta, which like Mt Dikte was in eastern Crete.

Two divergent reports (by Herodotus and Proclus) about the flight of Paris and Helen in the Kypria imply two different poems, perhaps one current in Cyprus and the other in Halicarnassus.

Objectives: To produce a robust measure of social inclusion [Social and Community Opportunities Profile (SCOPE)] that is multidimensional and captures multiple life domains; incorporates objective and subjective indicators of inclusion; has sound psychometric properties including responsiveness; facilitates benchmark comparisons with normative general population and mental health samples [including common mental disorder (CMD) and severe mental illness groups]; can be used with people with mental health problems receiving support from mental health services or not; and can be used across a range of community service settings. Design: Phase I: conceptual framework developed from a review of the literature and concept mapping. Phase II: questionnaire developed including UK national population surveys and other normative data. Pre-testing using cognitive appraisal and evaluation then pilot testing in a small convenience sample. Preliminary testing (following modification) in community (n = 252) and mental health service users (MHSUs) samples (n = 43). Data reduction including factor analysis and Mokken scaling for polytomous item response analysis then psychometric evaluation, including internal consistency and discriminant and construct validity. Test–retest reliability assessed in a convenience sample of students (n = 119). Final testing in clinical services including psychometric evaluation and responsiveness testing. Setting: The community sample was set in participants’ households across the UK. The MHSU sample was set in a south Wales resource centre. The student sample was set in a university. Participants: The community sample was randomly selected from the postal address file in five areas in England and Wales. Forty people in this sample were subgrouped as having a CMD based on their responses to the Mental Health Index five items. Two MHSU samples were obtained from existing services. Results: Psychometric testing on the field data from the SCOPE long version demonstrated good internal consistency of all scales (alpha ≥ 0.7), good construct validity, with SCOPE scales correlating highly with each other sharing between 40% and 61% of variance and a close but lesser association with community participation and social capital. Chi-squared tests on objective items and analysis of variance between groups on SCOPE scales demonstrated good discriminant validity between different mental health groups (and better than the Mokken scaling results). Acceptability was good, with 77% of the service user sample finding the SCOPE domains relevant. The number of items in SCOPE decreased from 121 to 48 following data reduction. Scales in the short version of SCOPE retained reasonable internal consistency (alpha between 0.60 and 0.75). Test–retest reliability demonstrated reliability over time, with strong associations between all items over a 2-week period. Repeating the discriminant validity tests on the short version demonstrates good discriminant validity between the mental health groups. Acceptability improved, with 90% of the sample describing questions as relevant to them. Conclusions: The main aim of producing an instrument with good psychometric properties for use in research and clinical settings, namely the SCOPE short version, was achieved. Ongoing data collection will enable responsiveness testing in the future. Further research is needed including larger samples of minority and disadvantaged groups, including those with physical illnesses and disabilities, and specific mental health diagnostic groups. Funding: The National Institute for Health Research Health Technology Assessment programme.

An inscription dating ca. 525-400 B.C. gives μαλος, which had several possible meanings, including Dorian heroic names.

We describe a technique of endoloop closure of a paraumbilical abdominal wall hernia defect when using 5 mm laparoscopic ports.

The space-filling fractal network in the human lung creates a remarkable distribution system for gas exchange. Landmark studies have illuminated how the fractal network guarantees minimum energy dissipation, slows air down with minimum hardware, maximizes the gas- exchange surface area, and creates respiratory flexibility between rest and exercise. In this paper, we investigate how the fractal architecture affects oxygen transport and exchange under varying physiological conditions, with respect to performance metrics not previously studied.We present a renormalization treatment of the diffusion-reaction equation which describes how oxygen concentrations drop in the airways as oxygen crosses the alveolar membrane system. The treatment predicts oxygen currents across the lung at different levels of exercise which agree with measured values within a few percent. The results exhibit wide-ranging adaptation to changing process parameters, including maximum oxygen uptake rate at minimum alveolar membrane permeability, the ability to rapidly switch from a low oxygen uptake rate at rest to high rates at exercise, and the ability to maintain a constant oxygen uptake rate in the event of a change in permeability or surface area. We show that alternative, less than space-filling architectures perform sub-optimally and that optimal performance of the space-filling architecture results from a competition between underexploration and overexploration of the surface by oxygen molecules.

BackgroundMarkers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease.Methods and findingsA meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30-300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23-1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose-response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30-1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87-2.52). Sensitivity analysis indicated no important differences in prespecified subgroups.ConclusionThese data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual's cardiovascular risk.

Quorum sensing (QS) is a mechanism by which gram-negative bacteria regulate their gene expression by making use of cell density. QS is triggered by a small molecule known as an autoinducer. Typically, gram-negative bacteria such as Vibrio produce signaling molecules called acyl homoserine lactones (AHLs). However, their levels are very low, making them difficult to detect. We used thin layer chromatography (TLC) to examine AHLs in different Vibrio species, such as Vibrio alginolyticus , Vibrio parahemolyticus , and Vibrio cholerae , against a standard- Chromobacterium violaceum. Further, AHLs were characterised by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC–MS). C4-HSL (N- butanoyl- L- homoserine lactone), C6-HSL (N- hexanoyl- L- homoserine lactone), 3-oxo-C8-HSL (N-(3-Oxooctanoyl)-DL-homoserine lactone), C8-HSL (N- octanoyl- L- homoserine lactone), C 1 10-HSL (N- decanoyl- L- homoserine lactone), C12-HSL (N- dodecanoyl- L- homoserine lactone) and C14-HSL (N- tetradecanoyl- L- homoserine lactone) were identified from Vibrio. These results may provide a basis for blocking the AHL molecules of Vibrio , thereby reducing their pathogenicity and eliminating the need for antimicrobials. [ABSTRACT FROM AUTHOR]

Background - based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile (LQLP), the Manchester Short Assessment of Quality of Life (MANSA) has been developed as a condensed and slightly modified instrument for assessing quality of life. Its properties have been tested in a sample of community care patients. Method - Fifty-five randomly selected patients on the Care Programme Approach were interviewed using the LQLP, the MANSA and the Brief Psychiatric Rating Scale. Results - Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher (0.94 for the satisfaction mean score). Cronbach's alpha for satisfaction ratings was 0.74, and association with psychopathology was in line with results for LQLP as reported in the literature. Conclusions - The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains. Its psychometric properties appear satisfactory.