Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

Background
Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the eff ect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods
We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks’ and 22 weeks’ gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive1000 mg vitamin C and 400 IU vitamin E (a-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratifi ed by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defi ned as gestational hypertension with proteinuria. Analysis was by modifi ed intention to treat. This study is registered, ISRCTN27214045.

Findings
Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70)groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.

Interpretation
Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be benefi cial in women with a low antioxidant status at baseline needs further testing.

Who goes where? Young children's pathways through care in Northern Ireland

This is one of a series of articles reporting on the large-scale ‘Northern Ireland Care Pathways and Outcomes Study’ (McSherry et al, 2008). The study has been examining a population of young children (n=374) who were in care under five years of age in Northern Ireland, and initially followed them across a four-year period (2000-2004). It has mapped these young children’s care careers, and explored factors relating to five care pathways that these children progressed along, i.e. towards adoption; long-term non-relative foster care; long-term relative foster care; Residence Order; and return to birth parent/s. This paper will examine the children’s care pathway patterns from 2000 to 2004, and will identify the background factors that appear to have influenced their specific care pathway. These background factors relate to the age of child, length of time in care, the child’s health, the child’s behaviour and regional variation. The findings indicate that although the care pathway patterns were to some extent similar to England and Wales, there were differences apparent to the Northern Ireland context.

Shark virgin birth produces multiple, viable offspring

Facultative automictic parthenogenesis has only recently been confirmed in the most ancient jawed vertebrates, the chondrichthyan fishes (sharks, batoids, and chimeras). To date, however, in both documented cases, the females have only produced a single parthenogen offspring, and none of these have lived for more than 3 days. We present a genetically verified case of automictic parthenogenesis by a white-spotted bamboo shark (Chiloscyllium plagiosum), in which at least 2 parthenogens were produced and survived for 5 years or more. These findings demonstrate that some female sharks are capable of producing, multiple, viable offspring through parthenogenesis.

Quantifying Alcohol-Related Mortality: Should Alcohol-Related Contributory Causes of Death be Included?

Aims: The aim of the study was to assess whether alcohol-related mortality data in the UK should be extended to include contributory as well as underlying cause of death. Methods: A total of 101,320 deaths registered in Northern Ireland between 2001 and 2007 were analysed to determine the quantity and characteristics of those with an underlying or contributory alcohol-related cause of death. Results: Alcohol was found to be an underlying cause of death in 1690 cases (1.7% of deaths) and a contributory cause in a further 1105 cases. Analyses show that the addition of alcohol-related contributory causes of deaths would increase the male-female ratio, result in steeper socio-economic gradients and amplify the apparent rate of increase of alcohol-related deaths. The significant contribution of alcohol to external causes of death, such as accidents and suicide, is also more evident. Conclusions: Using only underlying cause of death undoubtedly underestimates the burden of alcohol-related harm and may provide an inaccurate picture of those most likely to suffer from an alcohol-related death, especially among younger men.

Electromagnetic pulse compression and energy localization in quantum plasmas

The evolution of the intensity of a relativistic laser beam propagating through a dense quantum plasma is investigated, by considering different plasma regimes. A cold quantum fluid plasma and then a thermal quantum description(s) is (are) adopted, in comparison with the classical case of reference. Considering a Gaussian beam cross-section, we investigate both the longitudinal compression and lateral/longitudinal localization of the intensity of a finite-radius electromagnetic pulse. By employing a quantum plasma fluid model in combination with Maxwell's equations, we rely on earlier results on the quantum dielectric response, to model beam-plasma interaction. We present an extensive parametric investigation of the dependence of the longitudinal pulse compression mechanism on the electron density in cold quantum plasmas, and also study the role of the Fermi temperature in thermal quantum plasmas. Our numerical results show pulse localization through a series of successive compression cycles, as the pulse propagates through the plasma. A pulse of 100 fs propagating through cold quantum plasma is compressed to a temporal size of approximate to 1.35 attosecond and a spatial size of approximate to 1.08 10(-3) cm. Incorporating Fermi pressure via a thermal quantum plasma model is shown to enhance localization effects. A 100 fs pulse propagating through quantum plasma with a Fermi temperature of 350 K is compressed to a temporal size of approximate to 0.6 attosecond and a spatial size of approximate to 2.4 10(-3) cm. (c) 2010 Elsevier B.V. All rights reserved.

Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I 2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I 2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

Work-life Conflict and Social Inequality in Western Europe

Recent debates on time-use suggest that there is an inverse relationship between time poverty and income poverty (Aguiar and Hurst in Q J Econ C(3):969-1006, 2007), with Hammermesh and Lee (Rev Econ Stat 89(2):374-383, 2007) suggesting much time poverty is 'yuppie kvetch' or 'complaining'. Gershuny (Soc Res Int Q Soc Sci 72(2):287-314, 2005) argues that busyness is the 'badge of honour': being busy is now a positive, privileged position and it is high status people who work long hours and feel busy. Is this also true of work-life conflict? This paper explores the relationship between work-life tension and social inequality, as measured by social class, drawing on evidence from the European Social Survey. To what extent is work-life conflict a problem of the (comparatively) rich and privileged professional/managerial classes, and is this true across European countries? The countries selected offer a range of institutional and policy configurations to maximise variation. Using regression modelling of an index of subjective work-life conflict, we find that in all the countries under study, work-life conflict is higher among professionals than non-professionals. Part of this is explained by the fact that professionals work longer hours and experience more work pressure than other social classes, though the effect remains even after accounting for these factors. While levels of work-life conflict vary across the countries studied, country variation in class differences is modest. We consider other explanations of why professionals report higher work-life conflict and the implications of our findings for debates on social inequality.

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

Objectives: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate in paediatric patients. Patients and Methods: Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16-28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analysed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. Results: A one-compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (L/hr) = 11.4 × (WT /70.0)(0.75) and V/F (L) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 L/hr and 21.4 L, respectively, resulting in an elimination half-life of 11.2 hr. Conclusions: The range of estimated CL/F in the study population was 0.67-7.38 L/hr. The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients