Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families

A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. (1). The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. (2). However, the linkage disequilibrium (LD) among the SNPs in DTNBP1 as well as the pattern of significant SNP-schizophrenia association was complex. This raised several questions such as the number of susceptibility alleles that may be involved and the size of the region where the actual disease mutation(s) could be located. To address these questions, we performed different single-marker tests on the 12 previously studied and 2 new SNPs in DTNBP1 that were re-scored using an improved procedure, and performed a variety of haplotype analyses. The sample consisted of 268 Irish multiplex families selected for high density of schizophrenia. Results suggested a simple structure where the LD in the target region could be explained by 6 haplotypes that together accounted for 96% of haplotype diversity in the whole sample. From these six, a single high-risk haplotype was identified that showed a significant association with schizophrenia and explained the pattern of significant findings in the analyses with individual markers. This haplotype was 30 kb long, had a large effect, could be measured with two tag SNPs only, had a frequency of 6% in our sample, seemed to be of relatively recent origin in evolutionary terms, and was equally distributed over Ireland. Implications of these findings for follow-up and replication studies are discussed.

Risk of Several Cancers is Higher in Urban Areas after Adjusting for Socioeconomic Status. Results from a Two-Country Population-Based Study of 18 Common Cancers

Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural 15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation. © 2014 The New York Academy of Medicine.

Arsenic biogeochemistry as affected by phosphorus fertilizer addition, redox potential and pH in a west Bengal (India) soil

This laboratory experiment systematically examines arsenic, iron, and phosphorus solubilities in soil suspensions as affected by addition of phosphorus fertilizer under different redox potential (Eh) and pH conditions. Under aerobic conditions, As solubility was low, however, under moderately reducing conditions (0, -150 mV), As solubility significantly increased due to dissolution of iron oxy-hydroxides. Upon reduction to -250 mV, As solubility was controlled by the formation of insoluble sulfides, and as a result soluble As contents significantly decreased. Soluble Fe concentration increased from moderate to highly anaerobic conditions; however, it decreased under aerobic conditions likely due to formation of insoluble oxy-hydroxides. A low pH, 5.5, led to increased soluble concentrations of As, Fe, and P. Finally, addition of P-fertilizers resulted in higher soluble P and As, even though the concentration of As did not increased after an addition rate of 600 mg P kg(-1) soil. (c) 2006 Elsevier B.V. All rights reserved.

Applied physics: Trawling for complements

A method has been invented for determining nanoscale variations in the distribution of electric charge on surfaces. It has so far been used to examine specific inorganic materials, but could find widespread applications in imaging.

Simvastatin in the Acute Respiratory Distress Syndrome

Background

Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.

Methods

In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.

Results

The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.

Conclusions

Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.)

On the Exploitation of the Inherent Error Resilience of Wireless Systems under Unreliable Silicon

In this paper, we investigate the impact of circuit misbehavior due to parametric variations and voltage scaling on the performance of wireless communication systems. Our study reveals the inherent error resilience of such systems and argues that sufficiently reliable operation can be maintained even in the presence of unreliable circuits and manufacturing defects. We further show how selective application of more robust circuit design techniques is sufficient to deal with high defect rates at low overhead and improve energy efficiency with negligible system performance degradation.

Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia

Background Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.

Methods Adult sheep (30–40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10¹¹ CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10⁶ hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10⁶ hMSCs/kg, n=4.

Results By 24 h, the PaO₂/FiO₂ ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO₂/FiO₂ of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9–5.8] vs control: 6.7 g wet/g dry [IQR 6.4–7.5] (p=0.01)). The hMSCs had no adverse effects.

Conclusions Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.

Scyphozoan jellyfish provide short-term reproductive habitat for hyperiid amphipods in a temperate near-shore environment

Hyperiid amphipods (Order Amphipoda, Suborder Hyperiidea) are known to infest gelatinous zooplankton. However, the temporal backdrop to these associations is less clear, given that data are often gathered during discrete sampling events rather than over time. In general, hyperiids are considered to be pelagic: however, for individuals associated with metagenic jellyfishes in temperate shallow shelf seas, this may not always be the case, as the majority of their gelatinous hosts are present in the water column from spring to the onset of autumn. Here, we explored the temporal patterns of colonisation and overall duration of the association between Hyperia galba and 3 scyphozoan jellyfish species (Aurelia aurita, Cyanea capillata and C. lamarckii) in a temperate coastal system (Strangford Lough, Northern Ireland) during 2010 and 2012. Concomitantly, we used carbon and nitrogen stable isotope ratios to examine whether hyperiid infestation represented a permanent association with their host or was part of a more complex life history. We found that jellyfish were colonised by H. galba ca. 2 mo after they are first observed in the lough and that H. galba reached 100% prevalence in the different jellyfish species shortly before the medusae of each species disappeared from the water column. It is possible that some jellyfish overwintered in deeper water, prolonging the association between H. galba and their hosts. However, all the medusae sampled during the spring and early summer (whether they were newly emerged or had overwintered from the previous season) were not infected with hyperiids, suggesting that such behaviour was uncommon or that individuals had become dissociated from their host during the winter. Further evidence of temporary association came from stable isotope data, where δ13C and δ15N isotope ratios were indicative of feeding outside of their host prior to jellyfish colonisation. In combination, these findings suggest alternating habitat associations for H. galba, with the amphipods spending the majority of the year outside of the 3 scyphozoan species considered here.

An alkyne hydrosilylation–Hiyama coupling approach to highly functionalised 1,3-dienes

A high yielding and robust protocol for the stereodefined synthesis of 1,3-dienes has been established through a hydrosilylation–Hiyama coupling strategy. In all cases the products were formed as single E,E isomers and conditions are tolerant of a wide range of functional groups not compatible with other methods.

Young teenagers' experiences of domestic abuse

This article reports on the first findings from the Boys to Men Research Project. In total, 1143 pupils aged 13–14 years completed a questionnaire to assess their experiences of domestic abuse as victims, witnesses and perpetrators. Overall, 45% of pupils who had been in a dating relationship reported having been victimised, 25% having perpetrated it, with the only difference in rates of victimisation and perpetration between boys and girls being in relation to sexual victimisation. Of the whole sample, 34% reported having witnessed it in their own family. There was a relationship between victimisation and perpetration with the vast majority of perpetrators (92%) also reporting experiencing abuse from a boyfriend/girlfriend. There was also a relationship between experiencing abuse and help seeking from adults, with those who have been victimised less likely to say they would seek help if they were hit by a partner than those who had yet to experience any abuse. The relationship between help seeking and experiences of abuse is further complicated by gender, with girls twice as likely to seek help than boys, but with girls who have previously hit a partner among the most reticent group. The paper concludes with highlighting the implications of these findings for those undertaking preventative work in schools.