Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group.

In 1985 a second randomisation was initiated for women in the treatment arm of the Scottish Tamoxifen Trial either to stop tamoxifen at 5 years or to continue indefinitely. A preliminary analysis of outcome in 342 patients at a median follow-up of 6 years suggests that a worthwhile gain in disease control from continuing adjuvant tamoxifen beyond 5 years is unlikely. [Hazard ratio for events (relapse or death without relapse) is 1.27, 95% CI = 0.87 - 1.85.] There is a suggestion that therapy for longer than 5 years may increase the risk of endometrial carcinoma (P = 0.064)

The Quantity Theory of Money is Valid. The New Keynesians are Wrong!

We test the quantity theory of money (QTM) using a novel approach and a large new sample. We do not follow the usual approach of first differentiating the logarithm of the Cambridge equation to obtain an equation relating the growth rate of real GDP, the growth rate of money and inflation. These variables must then again be ‘integrated’ by averaging in order to obtain stable relationships. Instead we suggest a much simpler procedure for testing directly the stability of the coefficient of the Cambridge equation. For 125 countries and post-war data we find the coefficient to be surprisingly stable. We do not select for high inflation episodes as was done in most empirical studies; inflation rates do not even appear in our data set. Much work supporting the QTM has been done by economic historians and at the University of Chicago by Milton Friedman and his associates. The QTM was a foundation stone of the monetarist revolution. Subsequently belief in it waned. The currently dominant New Keynesian School, implicitly or explicitly denies the validity of the QTM. We survey this history and argue that the QTM is valid and New Keynesians are wrong

Low serum magnesium and 1-year mortality in alcohol withdrawal syndrome

Background: In 2014, the WHO reported that 6% of all deaths were attributable to excess alcohol consumption. The aim of the present study was to examine the relationship between serum magnesium concentrations and mortality in patients with alcohol withdrawal syndrome (AWS). Materials and methods: A retrospective review of 700 patients with documented evidence of previous AWS indicating a requirement for benzodiazepine prophylaxis or evidence of alcohol withdrawal syndrome between November 2014 and March 2015. Results: Of 380 patients included in the sample analysis, 64 (17%) were dead at 1 year following the time of treatment for AWS. The majority of patients had been prescribed thiamine (77%) and a proton pump inhibitor (66%). In contrast, the majority of patients had low circulating magnesium concentrations (2 (P  50 years (OR 3.37, 95% CI 1.52-7.48, P 2 (OR 3.10, 95% CI 1.38-6.94, P < 0.01) and magnesium < 0.75 mmol/L (OR 4.11, 95% CI 1.3-12.8, P < 0.05) remained independently associated with death at 1 year. Conclusion: Overall, 1-year mortality was significantly higher among those patients who were magnesium deficient (<0.75 mmol/L) when compared to those who were replete (≥0.75 mmol/L; P < 0.001)

The Halo and Rings of the Planetary Nebula NGC 40 in the Mid-Infrared

We present imaging and spectroscopy of NGC 40 acquired using the Spitzer Space Telescope (Spitzer), and the Infrared Space observatory (ISO). These are used to investigate the nature of emission from the central nebular shell, from the nebular halo, and from the associated circumnebular rings. It is pointed out that a variety of mechanisms may contribute to the mid-infrared (MIR) fluxes, and there is evidence for a cool dust continuum, strong ionic transitions, and appreciable emission by polycyclic aromatic hydrocarbons (PAHs). Prior observations at shorter wavelengths also indicate the presence of warmer grains, and the possible contribution of H2 transitions. It is suggested that an apparent jet-like structure to the NE of the halo represents one of the many emission spokes that permeate the shell. The spokes are likely to be caused by the percolation of UV photons through a clumpy interior shell, whilst the jet-like feature is enhanced due to locally elevated electron densities; a result of interaction between NGC 40 and the interstellar medium. It is finally noted that the presence of the PAH, 21 microns and 30 microns spectral features testifies to appreciable C/O ratios within the main nebular shell. Such a result is consistent with abundance determinations using collisionally excited lines, but not with those determined using optical recombination linesComment: 13 pages, 8 figures, Accepted for publication in MNRAS. 37 pages in arXi

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Mothers' accounts of their stillbirth experiences and of their subsequent relationships with their living infant:an interpretative phenomenological analysis

BACKGROUND: Due to contradictory findings regarding the effects of seeing and holding stillborn infants on women's worsening mental health symptoms, there is a lack of clear of guidance in stillbirth bereavement care. Although some current research examines this phenomenon we are still not certain of the meaning of such experiences to women and what effects there may be on her subsequent parenting. Thus the present study focuses on the meaning of the stillbirth experience to women and its influence on the subsequent pregnancy and subsequent parenting from the mothers' own experiences. METHODS: A purposive sample of six women who experienced a stillbirth during their first pregnancy and who then went on to give birth to a living child after a further pregnancy, took part in email interviews, providing rich and detailed experiential narratives about both the stillbirth itself, and their relationship with their living child. An Interpretive Phenomenological Analysis was carried out in order to focus on mothers making sense of such experiences. RESULTS: Analysis of written accounts led to the development of three overarching themes. In 'Broken Canopy', 'How This Happened' and 'Continuing Bonds', their accounts revealed an ongoing process where women accepted a new 'unsafe' view of the world, re-evaluated their view of self and others, and established relationships with both the deceased and the living infant. CONCLUSIONS: This study provided an insight into the stillbirth experience of mothers and its meaning to them with an existential focus. Typically the mother struggled with the contradictory process of accepting the existence of her deceased baby (this baby once lived) while being aware of the nonexistence (this baby). Meeting the dead baby was a crucial point at which the mother started processing her grief. The importance of individual differences in dealing with stressful situations was highlighted in terms of attachment strategies. Subsequent parenting experiences of mothers were very much influenced by their own previous experiences. Although some mothers managed to integrate this trauma into their life some remained very concerned and anxious about future and this anxiety then translated into their parenting experiences

Safety and Immunogenicity Following Administration of a Live, Attenuated Monovalent 2009 H1N1 Influenza Vaccine to Children and Adults in Two Randomized Controlled Trials

BACKGROUND: The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults. METHODS/PRINCIPAL FINDINGS: Two randomized, double-blind, placebo-controlled studies were completed in children (2-17 y) and adults (18-49 y). Subjects were assigned 4:1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1-8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: -6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: -9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: -5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: -0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred. CONCLUSIONS/SIGNIFICANCE: In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT00946101, NCT00945893

Empiric Antibiotic Therapy for Staphylococcus aureus Bacteremia May Not Reduce In-Hospital Mortality: A Retrospective Cohort Study

Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence factors in the infecting strain.We conducted a retrospective cohort study of adult patients admitted to a tertiary-care facility from January 1, 2003 to June 30, 2007, who had S. aureus bacteremia. Time to appropriate therapy was measured from blood culture collection to the receipt of antibiotics with in vitro activity to the infecting organism. Cox proportional hazard models were used to measure the association between receipt of appropriate empiric therapy and in-hospital mortality, statistically adjusting for patient and pathogen characteristics.Among 814 admissions, 537 (66%) received appropriate empiric therapy. Those who received appropriate empiric therapy had a higher hazard of 30-day in-hospital mortality (Hazard Ratio (HR): 1.52; 95% confidence interval (CI): 0.99, 2.34). A longer time to appropriate therapy was protective against mortality (HR: 0.79; 95% CI: 0.60, 1.03) except among the healthiest quartile of patients (HR: 1.44; 95% CI: 0.66, 3.15).Appropriate empiric therapy was not associated with decreased mortality in patients with S. aureus bacteremia except in the least ill patients. Initial broad antibiotic selection may not be widely beneficial

2016 International Land Model Benchmarking (ILAMB) Workshop Report

As earth system models (ESMs) become increasingly complex, there is a growing need for comprehensive and multi-faceted evaluation of model projections. To advance understanding of terrestrial biogeochemical processes and their interactions with hydrology and climate under conditions of increasing atmospheric carbon dioxide, new analysis methods are required that use observations to constrain model predictions, inform model development, and identify needed measurements and field experiments. Better representations of biogeochemistryclimate feedbacks and ecosystem processes in these models are essential for reducing the acknowledged substantial uncertainties in 21st century climate change projections