Family transitions and changes in drinking from adolescence through mid-life

AIMS: To examine how changes in social roles, particularly in the family, predict rises and falls in alcohol consumption from ages 16 to 50 years. DESIGN: Longitudinal data from the National Child Development Study. SETTING: The birth cohort includes 99% of British infants born in 1 week in 1958. Participants After initial assessment of 17,415 infants, the cohort was interviewed at ages 7, 11, 16, 23, 33, 42, 46, and 50. This study uses the six adolescent to adult waves (n = 7212 women, 7377 men). MEASUREMENTS: Alcohol use [i.e. quantity consumed in past week and heavy daily drinking), symptoms of problem drinking (i.e. Cut-down, Annoyed, Guilt, Eye-opener (CAGE)] and social roles (i.e. union formation, parenthood and employment). FINDINGS: Estimates from fixed-effects models demonstrate that alcohol use is lower when women reside with child(ren) under age 5, compared to occasions when they do not [estimate = -0.38, 95% confidence interval (CI) = -0.43, -0.32 for past week units; odds ratio (OR) = 0.47, CI = 0.36, 0.62 for heavy-daily drinking; OR = 0.66, CI = 0.50, 0.87 for CAGE symptoms]. Associations are similar for men (estimate = -0.29, CI = -0.36, -0.23; OR = 0.64, CI = 0.53, 0.77; OR = 0.69, CI = 0.51, 0.94, respectively). When women and men are married, working and residing with young child(ren), past week units (estimate = -0.51, CI = -0.61, -0.41 for women; estimate = -0.34, CI = -0.44, -0.25 for men), heavy-daily drinking (OR = 0.49, CI = 0.30, 0.79 for women; OR = 0.47, CI = 0.35, 0.64 for men) and CAGE (OR = 0.44, CI = 0.23, 0.83 for women; OR = 0.39, CI = 0.18, 0.82 for men) are lower compared to occasions when they are not in these roles. CONCLUSIONS: From late adolescence to mid-life, women and men in Britain are most at risk for higher levels of alcohol consumption and problem drinking when family roles are absent

The disappearance of the "revolving door" patient in Scottish general practice: successful policies

<b>Background</b> We describe the health of "revolving door" patients in general practice in Scotland, estimate changes in their number over the timescale of the study, and explore reasons for changes, particularly related to NHS and government policy.<p></p> <b>Methods</b> A mixed methods predominantly qualitative study, using a grounded theory approach, set in Scottish general practice. Semi-structured interviews were conducted with professional key informants, 6 Practitioner Services staff who administer the GP registration system and 6 GPs with managerial or clinical experience of working with "revolving door" patients. Descriptive statistical analysis and qualitative analysis of patient removal episodes linked with routine hospital admissions, outpatient appointments, drug misuse treatment episodes and deaths were carried out with cohorts of "revolving door" patients identified from 1999 to 2005 in Scotland.<p></p> <b>Results</b> A "revolving door" patient is removed 4 or more times from GP lists in 7 years. Patients had complex health issues including substance misuse, psychiatric and physical health problems and were at high risk of dying. There was a dramatic reduction in the number of "revolving door" patients during the course of the study.<p></p> <b>Conclusions</b> "Revolving door" patients in general practice had significant health problems. Their numbers have reduced dramatically since 2004 and this probably resulted from improved drug treatment services, pressure from professional bodies to reduce patient removals and the positive ethical regulatory and financial climate of the 2004 GMS GP contract. This is a positive development for the NHS

Human Computation and Convergence

Humans are the most effective integrators and producers of information, directly and through the use of information-processing inventions. As these inventions become increasingly sophisticated, the substantive role of humans in processing information will tend toward capabilities that derive from our most complex cognitive processes, e.g., abstraction, creativity, and applied world knowledge. Through the advancement of human computation - methods that leverage the respective strengths of humans and machines in distributed information-processing systems - formerly discrete processes will combine synergistically into increasingly integrated and complex information processing systems. These new, collective systems will exhibit an unprecedented degree of predictive accuracy in modeling physical and techno-social processes, and may ultimately coalesce into a single unified predictive organism, with the capacity to address societies most wicked problems and achieve planetary homeostasis.Comment: Pre-publication draft of chapter. 24 pages, 3 figures; added references to page 1 and 3, and corrected typ

Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus

© 2013 Al-Mahdawi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5 hmC and 5 mC.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS (CS), the Wellcome Trust [089757] (SA) and Ataxia UK (RMP) to MAP

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial.

BACKGROUND: Recent cardiovascular outcome trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. METHODS: DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2-4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin-angiotensin system inhibitor at enrolment. RESULTS: After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). CONCLUSION: DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes

Breakdown of Fermi-liquid theory in a cuprate superconductor

The behaviour of electrons in solids is remarkably well described by Landau's Fermi-liquid theory, which says that even though electrons in a metal interact they can still be treated as well-defined fermions, called ``quasiparticles''. At low temperature, the ability of quasiparticles to transport heat is strictly given by their ability to transport charge, via a universal relation known as the Wiedemann-Franz law, which no material in nature has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report on the first experimental test of the Wiedemann-Franz law in a cuprate superconductor, (Pr,Ce)$_2$CuO$_4$. Our study reveals a clear departure from the universal law and provides compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.Comment: 7 pages, 3 figure