The FENE dumbbell polymer model: existence and uniqueness of solutions for the momentum balance equation

We consider the FENE dumbbell polymer model which is the coupling of the incompressible Navier-Stokes equations with the corresponding Fokker-Planck-Smoluchowski di ffusion equation. We show global well-posedness in the case of a 2D bounded domain. We assume in the general case that the initial velocity is sufficiently small and the initial probability density is sufficiently close to the equilibrium solution; moreover an additional condition on the coeffcients is imposed. In the corotational case, we only assume that the initial probability density is sufficiently close to the equilibrium solution

Estimating the Total Number of Susceptibility Variants Underlying Complex Diseases from Genome-Wide Association Studies

Recently genome-wide association studies (GWAS) have identified numerous susceptibility variants for complex diseases. In this study we proposed several approaches to estimate the total number of variants underlying these diseases. We assume that the variance explained by genetic markers (Vg) follow an exponential distribution, which is justified by previous studies on theories of adaptation. Our aim is to fit the observed distribution of Vg from GWAS to its theoretical distribution. The number of variants is obtained by the heritability divided by the estimated mean of the exponential distribution. In practice, due to limited sample sizes, there is insufficient power to detect variants with small effects. Therefore the power was taken into account in fitting. Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted. The effects of false positive variants were removed by considering the local false discovery rates. In addition, we developed an alternative approach by directly fitting the z-statistics from GWAS to its theoretical distribution. In all cases, the “winner's curse” effect was corrected analytically. Confidence intervals were also derived. Simulations were performed to compare and verify the performance of different estimators (which incorporates various means of winner's curse correction) and the coverage of the proposed analytic confidence intervals. Our methodology only requires summary statistics and is able to handle both binary and continuous traits. Finally we applied the methods to a few real disease examples (lipid traits, type 2 diabetes and Crohn's disease) and estimated that hundreds to nearly a thousand variants underlie these traits

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

Social norms and cultural diversity in the development of third-party punishment

Human cooperation is probably supported by our tendency to punish selfishness in others. Social norms play an important role in motivating third-party punishment (TPP), and also in explaining societal differences in prosocial behaviour. However, there has been little work directly linking social norms to the development of TPP across societies. In this study, we explored the impact of normative information on the development of TPP in 603 children aged 4-14, across six diverse societies. Children began to perform TPP during middle childhood, and the developmental trajectories of this behaviour were similar across societies. We also found that social norms began to influence the likelihood of performing TPP during middle childhood in some of these societies. Norms specifying the punishment of selfishness were generally more influential than norms specifying the punishment of prosocial behaviour. These findings support the view that TPP of selfishness is important in all societies, and its development is shaped by a shared psychology for responding to normative information. Yet, the results also highlight the important role that children’s prior knowledge of local norms may play in explaining societal variation in the development of both TPP and prosociality

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

The contribution of genetic variants to disease depends on the ruler

Our understanding of the genetic basis of disease has evolved from descriptions of overall heritability or familiality to the identification of large numbers of risk loci. One can quantify the impact of such loci on disease using a plethora of measures, which can guide future research decisions. However, different measures can attribute varying degrees of importance to a variant. In this Analysis, we consider and contrast the most commonly used measures-specifically, the heritability of disease liability, approximate heritability, sibling recurrence risk, overall genetic variance using a logarithmic relative risk scale, the area under the receiver-operating curve for risk prediction and the population attributable fraction-and give guidelines for their use that should be explicitly considered when assessing the contribution of genetic variants to disease

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population.</p> <p>Methods</p> <p>The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system.</p> <p>Results</p> <p>As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA_{(rs8087945-rs12456774)}, haplotypes AG_{(rs8087945-rs12456774)}and GA_{(rs8087945-rs12456774)}were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively.</p> <p>Conclusions</p> <p>Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.</p

Positioning discourse on homophobia in schools: what have lesbian and gay families got to say?

This paper reports findings from a study in England, which investigated the experiences of lesbian and gay parents in relation to homophobia in primary and secondary schools. The study was part of a larger European Union project investigating the impact of family and school alliances against homophobic and transphobic bullying in schools across six nation states. Qualitative in-depth semi-structured interviews with seven lesbian and gay parents from five families were conducted to explore their unique experience and perspectives on these issues. Discourse analysis was used to facilitate understanding of how lesbian and gay families negotiated the outsider/insider and public/private spheres of the school and communities of which they were a part. Parents identified a number of strategies to address their experiences of homophobia within schools. The findings have implications for how social work recognises and promotes diversity and equality when working with lesbian, gay, bisexual and transgender families, as social workers have a powerful role in supporting families. This involves recognising the strengths of lesbian, gay, bisexual and transgender families in their assessments

Positioning discourse on homophobia in schools: What have lesbian and gay families got to say?

This paper reports findings from a study in England, which investigated the experiences of lesbian and gay parents in relation to homophobia in primary and secondary schools. The study was part of a larger European Union project investigating the impact of family and school alliances against homophobic and transphobic bullying in schools across six nation states. Qualitative in-depth semi-structured interviews with seven lesbian and gay parents from five families were conducted to explore their unique experience and perspectives on these issues. Discourse analysis was used to facilitate understanding of how lesbian and gay families negotiated the outsider/insider and public/private spheres of the school and communities of which they were a part. Parents identified a number of strategies to address their experiences of homophobia within schools. The findings have implications for how social work recognises and promotes diversity and equality when working with lesbian, gay, bisexual and transgender families, as social workers have a powerful role in supporting families. This involves recognising the strengths of lesbian, gay, bisexual and transgender families in their assessments