SOCIAL HOUSING ALLOCATION IN SCOTLAND : THE ADVERSE SELECTION ISSUES

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A genome-wide association study for late-onset Alzheimer's disease using DNA pooling

Background: Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case – control sample, reducing costs through the use of DNA pooling. Methods: DNA samples were collected from 1,082 individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to 95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and ethnicity. Equimolar amounts of each DNA sample were added to either a case or control pool. The pools were genotyped using Illumina HumanHap300 and Illumina Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from the pooling data were identified and then individually genotyped in the case – control sample used to construct the pools. Results: Highly significant association with LOAD was observed at the APOE locus confirming the validity of the pooled genotyping approach. For 109 SNPs outside the APOE locus, we obtained uncorrected p-values ≤ 0.05 for 74 after individual genotyping. To further test these associations, we added control data from 1400 subjects from the 1958 Birth Cohort with the evidence for association increasing to 3.4 × 10-6 for our strongest finding, rs727153. rs727153 lies 13 kb from the start of transcription of lecithin retinol acyltransferase (phosphatidylcholine – retinol O-acyltransferase, LRAT). Five of seven tag SNPs chosen to cover LRAT showed significant association with LOAD with a SNP in intron 2 of LRAT, showing greatest evidence of association (rs201825, p-value = 6.1 × 10-7). Conclusion: We have validated the pooling method for GWA studies by both identifying the APOE locus and by observing a strong enrichment for significantly associated SNPs. We provide evidence for LRAT as a novel candidate gene for LOAD. LRAT plays a prominent role in the Vitamin A cascade, a system that has been previously implicated in LOAD

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

<p>Abstract</p> <p>Background</p> <p>The function and viability of cultured, transplanted, or encapsulated pancreatic islets is often limited by hypoxia because these islets have lost their vasculature during the isolation process and have to rely on gradient-driven passive diffusion, which cannot provide adequate oxygen transport. Pancreatic islets (islets of Langerhans) are particularly susceptible due to their relatively large size, large metabolic demand, and increased sensitivity to hypoxia. Here, finite element method (FEM) based multiphysics models are explored to describe oxygen transport and cell viability in avascular islets both in static and in moving culture media.</p> <p>Methods</p> <p>Two- and three-dimensional models were built in COMSOL Multiphysics using the convection and diffusion as well as the incompressible Navier-Stokes fluid dynamics application modes. Oxygen consumption was assumed to follow Michaelis-Menten-type kinetics and to cease when local concentrations fell below a critical threshold; in a dynamic model, it was also allowed to increase with increasing glucose concentration.</p> <p>Results</p> <p>Partial differential equation (PDE) based exploratory cellular-level oxygen consumption and cell viability models incorporating physiologically realistic assumptions have been implemented for fully scaled cell culture geometries with 100, 150, and 200 <it>μ</it>m diameter islets as representative. Calculated oxygen concentrations and intra-islet regions likely to suffer from hypoxia-related necrosis obtained for traditional flask-type cultures, oxygen-permeable silicone-rubber membrane bottom cultures, and perifusion chambers with flowing media and varying incoming glucose levels are presented in detail illustrated with corresponding colour-coded figures and animations.</p> <p>Conclusion</p> <p>Results of the computational models are, as a first estimate, in good quantitative agreement with existing experimental evidence, and they confirm that during culture, hypoxia is often a problem for non-vascularised islet and can lead to considerable cell death (necrosis), especially in the core region of larger islets. Such models are of considerable interest to improve the function and viability of cultured, transplanted, or encapsulated islets. The present implementation allows convenient extension to true multiphysics applications that solve coupled physics phenomena such as diffusion and consumption with convection due to flowing or moving media.</p

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Complex Calculations: How Drug Use During Pregnancy Becomes a Barrier to Prenatal Care

Pregnant women who use drugs are more likely to receive little or no prenatal care. This study sought to understand how drug use and factors associated with drug use influence women’s prenatal care use. A total of 20 semi-structured interviews and 2 focus groups were conducted with a racially/ethnically diverse sample of low-income women using alcohol and drugs in a California county. Women using drugs attend and avoid prenatal care for reasons not connected to their drug use: concern for the health of their baby, social support, and extrinsic barriers such as health insurance and transportation. Drug use itself is a barrier for a few women. In addition to drug use, women experience multiple simultaneous risk factors. Both the drug use and the multiple simultaneous risk factors make resolving extrinsic barriers more difficult. Women also fear the effects of drug use on their baby’s health and fear being reported to Child Protective Services, each of which influence women’s prenatal care use. Increasing the number of pregnant women who use drugs who receive prenatal care requires systems-level rather than only individual-level changes. These changes require a paradigm shift to viewing drug use in context of the person and society and acceptance of responsibility for unintended consequences of public health bureaucratic procedures and messages about effects of drug use during pregnancy

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg  = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases

'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study

Background: \u27MRI negative PET positive temporal lobe epilepsy\u27 represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures.Methods: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed.Results: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p &lt; 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p &lt; 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p &lt; 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p &lt; 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula.Conclusion: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.<br /