Optimal Credit Rationing in Not-For-Profit Financial Institutions

We examine the dynamic optimization problem for not-for-profit financial institutions (NFPs) that maximize consumer surplus, not profits. We characterize the optimal dynamic policy and find that it involves credit rationing. Interest rates set by mature NFPs will typically be more favorable to customers than market rates, as any surplus is distributed in the form of interest rate subsidies, with credit rationing being required to prevent these subsidies from distorting loan volumes from their optimal levels. Rationing overcomes a fundamental problem in NFPs; it allows them to distribute the surplus without distorting the volume of activity from the efficient level.

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Accounts of debates in the House of Commons, March– April 1731, supplementary to the diary of the first earl of Egmont

John Perceval (1685–1748), 1st Viscount Perceval and (from 1733) 1st Earl of Egmont, was an assiduous recorder of his own life and times. His diaries, published by the Historical Manuscripts Commission from manuscripts in the British Library, are the best source for parliamentary debates at Westminster in the 1730s. For the years 1730-1733, when Perceval sat in the Commons (as an Irish peer) they are remarkably full. His practice seems to have been to prepare two versions (presumably on the basis of notes taken in the House), the first attributing speeches to individuals, and the second, entered up in the diary, which listed speakers and summarized all arguments on each side. His letterbooks for 1731 contain accounts of five debates that embody his first editing process, with speeches attributed to individuals. They were sent to an Irish correspondent, Marmaduke Coghill, and largely omitted from the diary because Perceval had already transcribed them elsewhere. They are new to historians and cast light on two main issues: the unsuccessful attempts by Perceval and the ‘Irish lobby’ to persuade the British parliament to settle the Irish woollen trade, a question bedevilling Anglo-Irish relations in this period; and an attempt by the opposition to stir up anger against perceived Spanish aggression against Gibraltar. One of the most interesting features is the insight afforded into the Commons performances of Sir Robert Walpole: his management of debates, his own style of speaking, and his sharp exchanges with opponents like William Pulteney.

A material model for multiaxial stretching and stress relaxation of polypropylene under process conditions

Polypropylene sheets have been stretched at 160 °C to a state of large biaxial strain of extension ratio 3, and the stresses then allowed to relax at constant strain. The state of strain is reached via a path consisting of two sequential planar extensions, the second perpendicular to the first, under plane stress conditions with zero stress acting normal to the sheet. This strain path is highly relevant to solid phase deformation processes such as stretch blow moulding and thermoforming, and also reveals fundamental aspects of the flow rule required in the constitutive behaviour of the material. The rate of decay of stress is rapid, and such as to be highly significant in the modelling of processes that include stages of constant strain. A constitutive equation is developed that includes Eyring processes to model both the stress relaxation and strain rate dependence of the stress. The axial and transverse stresses observed during loading show that the use of a conventional Levy-Mises flow rule is ineffective, and instead a flow rule is used that takes account of the anisotropic state of the material via a power law function of the principal extension ratios. Finally the constitutive model is demonstrated to give quantitatively useful representation of the stresses both in loading and in stress relaxation.

Strategies for multivessel revascularization in patients with diabetes

In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100kb), rare copy number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1,564 cases and 1,748 controls all from Ireland, and further extended the analysis to include an additional 5,196 UK controls. We found association with duplications at chr20p12.2 (P=0.007) and evidence of replication in large independent European schizophrenia (P=0.052) and UK bipolar disorder case-control cohorts (P=0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11,707 cases and 10 carriers in 21,204 controls (meta-analysis CMH P value=2x10(-4) (odds ratio (OR)=11.3, 95% CI=3.7, ∞)). Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68Mb with similar breakpoints across samples. By haplotype analysis and sequencing we identified a tandem ∼149kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P=2.5x10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.

Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. 

Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10⁴ colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. 

Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). 

Conclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.