Diabetic retinopathy and socioeconomic deprivation in Gloucestershire

Objectives To investigate socioeconomic variations in diabetes prevalence, uptake of screening for diabetic retinopathy, and prevalence of diabetic retinopathy. Methods The County of Gloucestershire formed the setting of the study. A cross-sectional study of people with diabetes was done on a countywide retinopathy-screening database. Diabetes prevalence with odds ratios, uptake of screening, prevalence of any retinopathy and prevalence of sight-threatening retinopathy at screening were compared for different area deprivation quintiles. Logistic regression was used to adjust for confounding. Results With each increasing quintile of deprivation, diabetes prevalence increased (odds ratio 0.84), the probability of having been screened for diabetic retinopathy decreased (odds ratio 1.11), and the prevalence of sight-threatening diabetic retinopathy among screened patients increased (odds ratio of 0.98), while the prevalence of non-sight-threatening diabetic retinopathy remained unchanged with each increasing quintile of deprivation. Conclusion Sight-threatening diabetic retinopathy was associated with socioeconomic deprivation, but non-sight-threatening diabetic retinopathy was not. Uptake of screening was inversely related to socioeconomic deprivation

Sponsored by ASABE Galt House

Abstract. Several studies were conducted by Forest Service researchers and University and Industrial collaborators that investigated the potential for lessening soil surface disturbances and compaction in forest operations through modifications of machine components or harvest systems. Specific machine modifications included change in tire size, use of dual tire systems, reduction of tire inflation pressures, reductions in load size and ground pressure. Soil surface disturbances were most evident in sites with high soil moisture content that were lessened by lowering tire inflation pressures or using a dual tire configuration. Traffic intensity increased rutting potential of harvest sites, especially with the use of narrow tires. Traffic intensities varied spatially and in intensity in clear cut harvest operations with intensities that ranged between none to 100 or more. Soil physical properties responded to choice of tire size and inflation pressure with narrower tires and/or higher inflation pressures associated with increased soil compaction. Soil disturbance data collected in three clear cut operations in Alabama indicated no differences among the operations by location, but soil response varied depending on site properties. Soil physical properties did not necessarily reflect the intensity of soil disturbance

Cosmic D-Strings and Vortons in Supergravity

Recent developments in string inspired models of inflation suggest that D-strings are formed at the end of inflation. Within the supergravity model of D-strings there are 2(n-1) chiral fermion zero modes for a D-string of winding n. Using the bounds on the relic vorton density, we show that D-strings with winding number n>1 are more strongly constrained than cosmic strings arising in cosmological phase transitions. The D-string tension of such vortons, if they survive until the present, has to satisfy 8\pi G_N \mu \lesssim p 10^{-26} where p is the intercommutation probability. Similarly, D-strings coupled with spectator fermions carry currents and also need to respect the above bound. D-strings with n=1 do not carry currents and evade the bound. We discuss the coupling of D-strings to supersymmetry breaking. When a single U(1) gauge group is present, we show that there is an incompatibility between spontaneous supersymmetry breaking and cosmic D-strings. We propose an alternative mechanism for supersymmetry breaking, which includes an additional U(1), and might alleviate the problem. We conjecture what effect this would have on the fermion zero modes.Comment: 11 page

Early growth response gene-2 (Egr-2) regulates the development of B and T cells

The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund

Predictive significance of the six-minute walk distance for long-term survival in chronic hypercapnic respiratory failure

Background: The 6-min walk distance ( 6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease ( COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure ( CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation ( NIV) comprising COPD ( n = 197), restrictive diseases ( RD; n = 112) and obesity-hypoventilation- syndrome ( OHS; n = 115), the prognostic value of 6-MWD for long- term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD ( median 280 m; quartiles 204/350 m) and RD ( 290 m; 204/362 m) compared to OHS ( 360 m; 275/440 m; p <0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s ( p <0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median {[} p <0.001, hazard ratio ( HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long- term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF. Copyright (C) 2007 S. Karger AG, Basel

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

SimHap GUI: An intuitive graphical user interface for genetic association analysis

<p>Abstract</p> <p>Background</p> <p>Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the <it>SimHap </it>package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool.</p> <p>Results</p> <p>We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the <it>SimHap </it>R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress.</p> <p>Conclusion</p> <p>SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.</p

Comparing six evolutionary population synthesis models through spectral synthesis on galaxies

We compare six popularly used evolutionary population synthesis (EPS) models (BC03, CB07, Ma05, GALEV, GRASIL, Vazdekis/Miles) through fitting the full optical spectra of six representative types of galaxies (star-forming and composite galaxies, Seyfert 2s, LINERs, E+A and early-type galaxies), which are taken from the Sloan Digital Sky Survey (SDSS). Throughout our paper, we use the simple stellar populations (SSPs) from each EPS model and the software STARLIGHT to do our fits. Our main results are: Using different EPS models the resulted numerical values of contributed light fractions change obviously, even though the dominant populations are consistent. The stellar population synthesis does depend on the selection of age and metallicity, while it does not depend on the stellar evolution track much. The importance of young populations decreases from star-forming, composite, Seyfert 2, LINER to early-type galaxies, and E+A galaxies lie between composite galaxies and Seyfert 2s in most cases. We conclude that different EPS models do derive different stellar populations, so that it is not reasonable to directly compare stellar populations estimated from different EPS models. To get reliable results, we should use the same EPS model for the compared samples.Comment: 13 pages, 4 figures, accepted for publication in A&

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia