Gene Expression Meta-Analysis Identifies VDAC1 as a Predictor of Poor Outcome in Early Stage Non-Small Cell Lung Cancer

Background: The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival.

Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials

Background: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials. Methods: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982). Findings: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0·73, 2p<0·00001), breast cancer mortality 24% versus 32% (ratio 0·73, 2p=0·0002), and death from any cause 25% versus 33% (ratio 0·75, 2p=0·0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0·82, 2p<0·00001), breast cancer mortality 36% versus 42% (ratio 0·86, 2p=0·0004), and death from any cause 39% versus 45% (ratio 0·87, 2p=0·0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy. Interpretation: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.

Parish farms and the poor law: a response to unemployment in rural southern England, c.1815-1835

Finding a ‘solution’ for the seemingly intractable problem of unemployment in post-Napoleonic rural England was the Holy Grail for many vestries. Yet, whilst we know much about the depth and consequences of unemployment, parish-driven schemes to set the poor to work have been subjected to remarkably little in the way of systematic study. This paper focuses on one such policy that remains entirely obscure: parish farms, the hiring of pre-existing farms or fields by the parish on which to employ those out of work. Bearing a ‘family resemblance’ to allotments and other land-based attempts to alleviate poverty, parish farms were unique in that they were managed in all regards by the parish and were an employment strategy as opposed to a scheme to supplement the incomes of the poor. Whilst the archive of parish farms is often frustratingly opaque, it is shown that before they were effectively outlawed by the passing of the New Poor Law, many southern parishes, especially in the Weald of Kent and Sussex, adopted the scheme, occasionally with great success.

WASP-31b: a low-density planet transiting a metal-poor, late-F-type dwarf star

We report the discovery of the low-density, transiting giant planet WASP-31b. The planet is 0.48 Jupiter masses and 1.55 Jupiter radii. It is in a 3.4-day orbit around a metal-poor, late-F-type, V = 11.7 dwarf star, which is a member of a common proper motion pair. In terms of its low density, WASP-31b is second only to WASP-17b, which is a more highly irradiated planet of similar mass. Based in part on observations made with the HARPS spectrograph on the 3.6-m ESO telescope (proposal 085.C-0393) and with the CORALIE spectrograph and the Euler camera on the 1.2-m Euler Swiss telescope, both at the ESO La Silla Observatory, Chile.The photometric time-series and radial-velocity data used in this work are available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/531/A60

Poor relief in the north of Ireland 1850-1921

This examines the way in which poor relief, and in particular the Poor Law, operated in the north of Ireland from the end of the Great Famine through to Partition. Drawing on a range of primary sources it develops a picture of relief patterns, exploring the ways in which the poor law was administered and the ways in which the poor utilised the limited relief options available to them. The chapter provides an analysis of how releif patterns in the north reacted to broader social and political change, developed over time and compared to other regions within Ireland.

Poverty and power: the Irish Poor Law in a north Antrim town 1861-1921

This examines the workings of the Irish Poor Law in the town of Ballymoney, Co. Antrim, during the period between the end of the Great Famine and Partition. It focuses both on those who administered and those who used the poor law and argues that for the former it provided an important route into local politics and for the latter it represented a crucial strand in the limited strategies for survival open to them. It also demonstrates the impact that local political outlook had on both the administration and the experience of poor relief.

Can Certain Genotypes Predispose to Poor Asthma Control in Children? A Pharmacogenetic Study of 9 Candiate Genes in Children with Difficult Asthma

Objective: We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods: A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Key Results: The results indicated that LTA4H A-9188.G, TNFa G-308.A and IL-4Ra A1727.G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p,0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Ra A1199.C, IL-4Ra T1570.C and IL- 4Ra A1727.G and CA haplotype of TNFa C-863.A and TNFa G-308.A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).

Conclusions and Clinical Relevance: The study revealed multiple SNPs and haplotypes in LTA4H, TNFa and IL4-Ra genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A- 9188.G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit. ©2013 Almomani et al.

Adherence to hand hygiene and risk factors for poor adherence in 13 Ontario acute care hospitals

Multicenter studies assessing hand hygiene adherence and risk factors for poor performance are scarce. In an observational study involving 13 hospitals across Ontario, Canada, we found a mean adherence rate of 31.2%, and that adherence was positively associated with nurses, single rooms, contact precautions, and the availability of alcohol hand rub dispensers. Copyright © 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.