Identification of co-regulated transcripts affecting male body size in Drosophila

Factor analysis is an analytic approach that describes the covariation among a set of genes through the estimation of 'factors', which may be, for example, transcription factors, microRNAs (miRNAs), and so on, by which the genes are co-regulated. Factor analysis gives a direct mechanism by which to relate gene networks to complex traits. Using simulated data, we found that factor analysis clearly identifies the number and structure of factors and outperforms hierarchical cluster analysis. Noise genes, genes that are not correlated with any factor, can be distinguished even when factor structure is complex. Applied to body size in Drosophila simulans, an evolutionarily important complex trait, a factor was directly associated with body size

Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia

Altered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types.A systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications (>20 % cases) associated with increased mRNA expression (ρ > 0.3, q < 10(-3)). Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers. Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours (P ≤ 0.01). Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia.This study reveals somatic genomic alterations underlying a pan-cancer metabolic shift and suggests genomic adaptation of these genes as a survival mechanism in hypoxic tumours

Rapid radiocarbon (14C) analysis of coral and carbonate samples using a continuous-flow accelerator mass spectrometry (CFAMS) system

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 26 (2011): PA4212, doi:10.1029/2011PA002174.Radiocarbon analyses of carbonate materials provide critical information for understanding the last glacial cycle, recent climate history and paleoceanography. Methods that reduce the time and cost of radiocarbon (14C) analysis are highly desirable for large sample sets and reconnaissance type studies. We have developed a method for rapid radiocarbon analysis of carbonates using a novel continuous-flow accelerator mass spectrometry (CFAMS) system. We analyzed a suite of deep-sea coral samples and compared the results with those obtained using a conventional AMS system. Measurement uncertainty is <0.02 Fm or 160 Ryr for a modern sample and the mean background was 37,800 Ryr. Radiocarbon values were repeatable and in good agreement with those from the conventional AMS system. Sample handling and preparation is relatively simple and the method offered a significant increase in speed and cost effectiveness. We applied the method to coral samples from the Eastern Pacific Ocean to obtain an age distribution and identify samples for further analysis. This paper is intended to update the paleoceanographic community on the status of this new method and demonstrate its feasibility as a choice for rapid and affordable radiocarbon analysis.This work was performed under NSF Cooperative Agreement OCE‐0753487, and also NSF‐OPP awards 0636787 and 0944474

Endotoxaemia in Haemodialysis: A Novel Factor in Erythropoetin Resistance?

Background/Objectives Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients. Methodology/Principal Findings 50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis. Conclusions This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin

The Dwarf Irregular/Wolf-Rayet Galaxy NGC4214: I. A New Distance, Stellar Content, and Global Parameters

We present the results of a detailed optical and near-IR study of the nearby star-forming dwarf galaxy NGC4214. We discuss the stellar content, drawing particular attention to the intermediate-age and/or old field stars, which are used as a distance indicator. On images obtained with the Hubble Space Telescope WFPC2 and NICMOS instruments in the equivalents of the V, R, I, J and H bands, the galaxy is well resolved into stars. We achieve limiting magnitudes of F814W ~27 in the WF chips and F110W ~25 in the NIC2. The optical and near-infrared color-magnitude diagrams confirm a core-halo galaxy morphology: an inner high surface-brightness young population within ~1.5' (~1 kpc) from the center of the galaxy, where the stars are concentrated in bright complexes along a bar-like structure; and a relatively low-surface-brightness, field-star population extending out to at least 8' (7 kpc). The color-magnitude diagrams of the core region show evidence of blue and red supergiants, main-sequence stars, asymptotic giant branch stars and blue loop stars. We identify some candidate carbon stars from their extreme near-IR color. The field-star population is dominated by the "red tangle", which contains the red giant branch. We use the I-band luminosity function to determine the distance based on the tip-of-the-red-giant-branch method: 2.7\pm0.3 Mpc. This is much closer than the values usually assumed in the literature, and we provide revised distance dependent parameters such as physical size, luminosity, HI mass and star-formation rate.Comment: 24 pages, 19 figures, accepted for publication in the July 2002 issue of AJ. Version with high resolution figures is available at http://www.astro.spbu.ru/staff/dio/preprints.htm

Dyadic adjustment, family coping, body image, quality of life and psychological morbidity in patients with psoriasis and their partners

Background Psoriasis is an incurable and chronic disease that includes unpredictable periods of remission and relapse requiring long-term therapy. Purpose This paper focuses on the relationship among family coping, psychological morbidity, body image, dyadic adjustment and quality of life in psoriatic patients and their partners. Method One hundred and one patients with psoriasis and 78 partners comprised the sample. They were regular users of the Dermatology Service of a Central Northern hospital in Portugal and a private dermatology clinic. Patients with psoriasis were assessed on anxiety, depression, body image, quality of life, dyadic adjustment and family coping. Partners were assessed on the same measures except body image and quality of life. Results A positive relationship among dyadic adjustment, psychological morbidity and family coping in patients and their partners was found. Also, patients with lower levels of quality of life had partners with higher levels of depressive and anxious symptoms. Better dyadic adjustment predicted family coping in the psoriatic patient. High levels of dyadic adjustment in patients and low partners’ trait anxiety predicted better dyadic adjustment in partners. Conclusion The results highlight the importance of incorporating family variables in psychological interventions in psoriasis’ care, particularly family coping and dyadic adjustment as well as the need for psychological intervention to focus both on patients and partners

A technical framework for costing health workforce retention schemes in remote and rural areas

<p>Abstract</p> <p>Background</p> <p>Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions.</p> <p>Methods</p> <p>This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.</p> <p>The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management.</p> <p>Results</p> <p>We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed.</p> <p>Conclusions</p> <p>These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.</p