Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

Formation of the South Pacific shallow salinity minimum: a Southern Ocean pathway to the tropical Pacific

In the eastern South Pacific Ocean, at a depth of about 200 m, a salinity minimum is found. This minimum is associated with a particular water mass, the “Shallow Salinity Minimum Water” (SSMW). SSMW outcrops in a fresh tongue (Smin) centered at about 45°S. The Smin appears to emanate from the eastern boundary, against the mean flow. The watermass transformation that creates SSMW and Smin is investigated here. The Smin and SSMW are transformed from saltier and warmer waters originating from the western South Pacific. The freshening and cooling occur when the water is advected eastward at the poleward side of the subtropical gyre. Sources of freshening and cooling are air–sea exchange and advection of water from south of the subtropical gyre. A freshwater and heat budget for the mixed layer reveals that both sources equally contribute to the watermass transformation in the mixed layer. The freshened and cooled mixed layer water is subducted into the gyre interior along the southern rim of the subtropical gyre. Subduction into the zonal flow restricts the transformation of interior properties to diffusion only. A simple advection/diffusion balance reveals diffusion coefficients of order 2000 m2 s−1. The tongue shape of the Smin is explained from a dynamical viewpoint because no relation to a positive precipitation–evaporation balance was found. Freshest Smin values are found to coincide with slowest eastward mixed layer flow that accumulates the largest amounts of freshwater in the mixed layer and creates the fresh tongue at the sea surface. Although the SSMW is the densest and freshest mode of water subducted along the South American coast, the freshening and cooling in the South Pacific affect a whole range of densities (25.0–26.8 kg m−3). The transformed water turns northward with the gyre circulation and contributes to the hydrographic structure of the gyre farther north. Because the South Pacific provides most of the source waters that upwell along the equatorial Pacific, variability in South Pacific hydrography may influence equatorial Pacific hydrography. Because one-half of the transformation is found to be controlled through Ekman transport, variability in wind forcing at the southern rim of the subtropical gyre may be a source for variability of the equatorial Pacific

Mechanisms of decadal variability in the Labrador Sea and the wider North Atlantic in a high-resolution climate model

A necessary step before assessing the performance of decadal predictions is the evaluation of the processes that bring memory to the climate system, both in climate models and observations. These mechanisms are particularly relevant in the North Atlantic, where the ocean circulation, related to both the Subpolar Gyre and the Meridional Overturning Circulation (AMOC), is thought to be important for driving significant heat content anomalies. Recently, a rapid decline in observed densities in the deep Labrador Sea has pointed to an ongoing slowdown of the AMOC strength taking place since the mid 90s, a decline also hinted by in-situ observations from the RAPID array. This study explores the use of Labrador Sea densities as a precursor of the ocean circulation changes, by analysing a 300-year long simulation with the state-of-the-art coupled model HadGEM3-GC2. The major drivers of Labrador Sea density variability are investigated, and are characterised by three major contributions. First, the integrated effect of local surface heat fluxes, mainly driven by year-to-year changes in the North Atlantic Oscillation, which accounts for 62% of the total variance. Additionally, two multidecadal-to-centennial contributions from the Greenland-Scotland Ridge outflows are quantified; the first associated with freshwater exports via the East Greenland Current, and the second with density changes in the Denmark Strait Overflow. Finally, evidence is shown that decadal trends in Labrador Sea densities are followed by important atmospheric impacts. In particular, a negative winter NAO response appears to follow the positive Labrador Sea density trends, and provides a phase reversal mechanism

Reconstructing extreme AMOC events through nudging of the ocean surface: a perfect model approach

While the Atlantic Meridional Overturning Circulation (AMOC) is thought to be a crucial component of the North Atlantic climate, past changes in its strength are challenging to quantify, and only limited information is available. In this study, we use a perfect model approach with the IPSL-CM5A-LR model to assess the performance of several surface nudging techniques in reconstructing the variability of the AMOC. Special attention is given to the reproducibility of an extreme positive AMOC peak from a preindustrial control simulation. Nudging includes standard relaxation techniques towards the sea surface temperature and salinity anomalies of this target control simulation, and/or the prescription of the wind-stress fields. Surface nudging approaches using standard fixed restoring terms succeed in reproducing most of the target AMOC variability, including the timing of the extreme event, but systematically underestimate its amplitude. A detailed analysis of the AMOC variability mechanisms reveals that the underestimation of the extreme AMOC maximum comes from a deficit in the formation of the dense water masses in the main convection region, located south of Iceland in the model. This issue is largely corrected after introducing a novel surface nudging approach, which uses a varying restoring coefficient that is proportional to the simulated mixed layer depth, which, in essence, keeps the restoring time scale constant. This new technique substantially improves water mass transformation in the regions of convection, and in particular, the formation of the densest waters, which are key for the representation of the AMOC extreme. It is therefore a promising strategy that may help to better constrain the AMOC variability and other ocean features in the models. As this restoring technique only uses surface data, for which better and longer observations are available, it opens up opportunities for improved reconstructions of the AMOC over the last few decades

Conservation benefits of a large marine protected area network that spans multiple ecosystems.

Marine protected areas (MPAs) are widely implemented tools for long-term ocean conservation and resource management. Assessments of MPA performance have largely focused on specific ecosystems individually and have rarely evaluated performance across multiple ecosystems either in an individual MPA or across an MPA network. We evaluated the conservation performance of 59 MPAs in California's large MPA network, which encompasses 4 primary ecosystems (surf zone, kelp forest, shallow reef, deep reef) and 4 bioregions, and identified MPA attributes that best explain performance. Using a meta-analytic framework, we evaluated the ability of MPAs to conserve fish biomass, richness, and diversity. At the scale of the network and for 3 of 4 regions, the biomass of species targeted by fishing was positively associated with the level of regulatory protection and was greater inside no-take MPAs, whereas species not targeted by fishing had similar biomass in MPAs and areas open to fishing. In contrast, species richness and diversity were not as strongly enhanced by MPA protection. The key features of conservation effectiveness included MPA age, preimplementation fisheries pressure, and habitat diversity. Important drivers of MPA effectiveness for single MPAs were consistent across MPAs in the network, spanning regions and ecosystems. With international targets aimed at protecting 30% of the world's oceans by 2030, MPA design and assessment frameworks should consider conservation performance at multiple ecologically relevant scales, from individual MPAs to MPA networks.fals

Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients

Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi‐institutional genome‐wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time‐to‐event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random‐effects meta‐analysis. The strongest association after meta‐analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41–2.18, p = 4.84 × 10−7). After imputation across this region, the combined analysis identified two SNPs that reached genome‐wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5–2.4; p = 1.3 × 10−8), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus

Collecting the Data

AbstractThis chapter discusses aspects related to data collection. It focuses, firstly, on sampling issues and, secondly, on the survey mode. Sampling issues include sample size and the type of sampling that enable precise estimates to be obtained. Regarding the survey mode, discrete choice experiments can be implemented by mail, telephone, face-to-face or web surveys. Each of these survey modes has its advantages and shortcomings. They are described and compared in the course of this chapter, addressing an important decision in the planning process of a discrete choice experiment

Early Results of Combined and Staged Coronary Bypass and Carotid Endarterectomy in Advanced Age Patients in Single Centre

Aim: In present study, we aimed to compare the staged and combined surgery in patients with severe carotid stenosis and coronary atherosclerosis and detect the factors affecting mortality and morbidity. Material and method: Between 2004 and 2008, 120 patients with predominant ischemic heart disease were enrolled to study. Patients were divided into three groups on basis surgery procedure. Group 1 (n=40) includeed patients had coronary artery disease without carotid disease underwent coronary artery by-pass graft (CABG) operation. Group 2 (n=40): included patients underwent combined surgery procedure including CABG and carotid endarterectomy (CEA). Patients underwent staged CABG and CEA were enrolled to Group 3 (n=40). All patients were in advanced aged and were had the same risk factors atributable atherosclerosis Results: Mean age of the patients in all groups were 68 +/- 6, 69 +/- 3, 71 +/- 2 respectively, and 83% were male. Eight patients died in all groups at follow-up(seven in group 2 and 3, and one in group 1) and the difference between both groups was statistically significant (p<0.001). The follow-up period in the intensive care unit, and hospitalization period were not statistically different between CABG group and combined CEA plus CABG group. Conclusion: We think that the results of staged or combined CABG plus CEA surgery are satisfactory in patients with severe carotid disease and advanced coronary artery disease. However, the mortality and morbidity in both procedures are higher than those of alone

Organ preservation surgery for laryngeal cancer

The principles of management of the laryngeal cancer have evolved over the recent past with emphasis on organ preservation. These developments have paralleled technological advancements as well as refinement in the surgical technique. The surgeons are able to maintain physiological functions of larynx namely speech, respiration and swallowing without compromising the loco-regional control of cancer in comparison to the more radical treatment modalities. A large number of organ preservation surgeries are available to the surgeon; however, careful assessment of the stage of the cancer and selection of the patient is paramount to a successful outcome. A comprehensive review of various organ preservation techniques in vogue for the management of laryngeal cancer is presented

Development and psychometric testing of an instrument to compare career choice influences and perceptions of nursing among healthcare students

Background: With the availability of more healthcare courses and an increased intake of nursing students, education institutions are facing challenges to attract school leavers to enter nursing courses. The comparison of career choice influences and perception of nursing among healthcare students can provide information for recruitment strategies. An instrument to compare the influences of healthcare career choice is lacking. The purpose of this study is to develop and evaluate the psychometric properties of an instrument to compare the influences of healthcare career choice with perceptions of nursing as a career choice. Methods: The study was conducted in two phases. In phase one, two sets of scales with parallel items that measure the influences of healthcare career choice and perceptions of nursing as a career choice were developed through an earlier qualitative study, literature review, and expert validation. Phase two involved testing the construct validity, concurrent validity and reliability with a convenience sample of 283 first year healthcare students who were recruited at two education institutions in Singapore. Results: An exploratory factor analysis revealed 35-parallel items in a six-factor solution (personal interest, prior healthcare exposure, self-efficacy, perceived nature of work, job prospects, and social influences) that explained 59 and 64% of the variance for healthcare career choice and nursing as a career choice respectively. A high correlation (r = 0.76, p \u3c 0.001) was obtained with an existing tool, confirming the concurrent validity. The internal consistency was sufficient with Cronbach’s alpha of 0.93 for healthcare career choice and 0.94 for nursing as a career choice. The test-retest reliability was acceptable with an Intraclass Correlation Coefficient of 0.63 for healthcare career choice and 0.60 for nursing as a career choice. Conclusions: The instrument provides opportunities for understanding the differences between influences of healthcare career choice and perceptions of nursing as a career choice. This comparative understanding of career choice influences can guide educator and policy-makers on nursing recruitmen