A 15.65 solar mass black hole in an eclipsing binary in the nearby spiral galaxy Messier 33

Stellar-mass black holes are discovered in X-ray emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses >10 solar masses, which is consistent with the fact that the most massive stellar black holes known so all have masses within 1 sigma of 10 solar masses. Here we report a mass of 15.65 +/- 1.45 solar masses for the black hole in the recently discovered system M33 X-7, which is located in the nearby galaxy Messier 33 (M33) and is the only known black hole that is in an eclipsing binary. In order to produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45 day orbit about its 70.0 +/- 6.9 solar mass companion, there must have been a ``common envelope'' phase of evolution in which a significant amount of mass was lost from the system. We find the common envelope phase could not have occured in M33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.Comment: To appear in Nature October 18, 2007. Four figures (one color figure degraded). Differs slightly from published version. Supplementary Information follows in a separate postin

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Profiles of physical, emotional and psychosocial wellbeing in the Lothian birth cohort 1936

<p>Abstract</p> <p>Background</p> <p>Physical, emotional, and psychosocial wellbeing are important domains of function. The aims of this study were to explore the existence of separable groups among 70-year olds with scores representing physical function, perceived quality of life, and emotional wellbeing, and to characterise any resulting groups using demographic, personality, cognition, health and lifestyle variables.</p> <p>Methods</p> <p>We used latent class analysis (LCA) to identify possible groups.</p> <p>Results</p> <p>Results suggested there were 5 groups. These included High (n = 515, 47.2% of the sample), Average (n = 417, 38.3%), and Poor Wellbeing (n = 37, 3.4%) groups. The two other groups had contrasting patterns of wellbeing: one group scored relatively well on physical function, but low on emotional wellbeing (Good Fitness/ Low Spirits,n = 60, 5.5%), whereas the other group showed low physical function but relatively well emotional wellbeing (Low Fitness/Good Spirits, n = 62, 5.7%). Salient characteristics that distinguished all the groups included smoking and drinking behaviours, personality, and illness.</p> <p>Conclusions</p> <p>Despite there being some evidence of these groups, the results also support a largely one-dimensional construct of wellbeing in old age—for the domains assessed here—though with some evidence that some individuals have uneven profiles.</p

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

Quantum phase transitions of light

Recently, condensed matter and atomic experiments have reached a length-scale and temperature regime where new quantum collective phenomena emerge. Finding such physics in systems of photons, however, is problematic, as photons typically do not interact with each other and can be created or destroyed at will. Here, we introduce a physical system of photons that exhibits strongly correlated dynamics on a meso-scale. By adding photons to a two-dimensional array of coupled optical cavities each containing a single two-level atom in the photon-blockade regime, we form dressed states, or polaritons, that are both long-lived and strongly interacting. Our zero temperature results predict that this photonic system will undergo a characteristic Mott insulator (excitations localised on each site) to superfluid (excitations delocalised across the lattice) quantum phase transition. Each cavity's impressive photon out-coupling potential may lead to actual devices based on these quantum many-body effects, as well as observable, tunable quantum simulators. We explicitly show that such phenomena may be observable in micro-machined diamond containing nitrogen-vacancy colour centres and superconducting microwave strip-line resonators.Comment: 11 pages, 5 figures (2 in colour

Combining functional weed ecology and crop stable isotope ratios to identify cultivation intensity: a comparison of cereal production regimes in Haute Provence, France and Asturias, Spain

This investigation combines two independent methods of identifying crop growing conditions and husbandry practices—functional weed ecology and crop stable carbon and nitrogen isotope analysis—in order to assess their potential for inferring the intensity of past cereal production systems using archaeobotanical assemblages. Present-day organic cereal farming in Haute Provence, France features crop varieties adapted to low-nutrient soils managed through crop rotation, with little to no manuring. Weed quadrat survey of 60 crop field transects in this region revealed that floristic variation primarily reflects geographical differences. Functional ecological weed data clearly distinguish the Provence fields from those surveyed in a previous study of intensively managed spelt wheat in Asturias, north-western Spain: as expected, weed ecological data reflect higher soil fertility and disturbance in Asturias. Similarly, crop stable nitrogen isotope values distinguish between intensive manuring in Asturias and long-term cultivation with minimal manuring in Haute Provence. The new model of cereal cultivation intensity based on weed ecology and crop isotope values in Haute Provence and Asturias was tested through application to two other present-day regimes, successfully identifying a high-intensity regime in the Sighisoara region, Romania, and low-intensity production in Kastamonu, Turkey. Application of this new model to Neolithic archaeobotanical assemblages in central Europe suggests that early farming tended to be intensive, and likely incorporated manuring, but also exhibited considerable variation, providing a finer grained understanding of cultivation intensity than previously available

A five-year review of burn injuries in Irrua

<p>Abstract</p> <p>Background</p> <p>The management of burns remains a challenge in developing countries. Few data exist to document the extent of the problem. This study provides data from a suburban setting by documenting the epidemiology of burn injury and ascertaining outcome of management. This will help in planning strategies for prevention of burns and reducing severity of complications.</p> <p>Methods</p> <p>A total of 72 patients admitted for burns between January 1st, 2002 and December 31st, 2006 at the Irrua specialist teaching hospital were studied retrospectively. Sources of information were the case notes and operation registers. Data extracted included demographics as well as treatment methods and outcome</p> <p>Results</p> <p>The results revealed male to female ratio of 2.1:1. Over 50% of the injuries occurred at home. There was a seasonal variation with over 40% of injuries occurring between November and January. The commonest etiologic agent was flame burn from kerosene explosion. There were 7 deaths in the series.</p> <p>Conclusion</p> <p>Burns are preventable. We recommend adequate supply of unadulterated petroleum products and establishment of burn centers.</p

Does clinical equipoise apply to cluster randomized trials in health research?

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, Weijer and colleagues set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the third of the questions posed, namely, does clinical equipoise apply to CRTs in health research? The ethical principle of beneficence is the moral obligation not to harm needlessly and, when possible, to promote the welfare of research subjects. Two related ethical problems have been discussed in the CRT literature. First, are control groups that receive only usual care unduly disadvantaged? Second, when accumulating data suggests the superiority of one intervention in a trial, is there an ethical obligation to act

How does subjective well-being evolve with age? A literature review

This literature review provides an overview of the theoretical and empirical research in several disciplines on the relation between ageing and subjective well-being, i.e., how subjective well-being evolves across the lifespan. Because of the different methodologies, data sets and samples used, comparison among disciplines and studies is difficult. However, extant studies do show either a U-shaped, inverted U-shaped or linear relation between ageing and subjective well-being

Development and Evaluation of a Palliative Medicine Curriculum for Third-Year Medical Students

Abstract Objective: To assess the impact, retention, and magnitude of effect of a required didactic and experiential palliative care curriculum on third-year medical students' knowledge, confidence, and concerns about end-of-life care, over time and in comparison to benchmark data from a national study of internal medicine residents and faculty. Design: Prospective study of third-year medical students prior to and immediately after course completion, with a follow-up assessment in the fourth year, and in comparison to benchmark data from a large national study. Setting: Internal Medicine Clerkship in a public accredited medical school. Participants: Five hundred ninety-three third-year medical students, from July 2002 to December 2007. Main outcome measures: Pre- and postinstruction performance on: knowledge, confidence (self-assessed competence), and concerns (attitudes) about end-of-life care measures, validated in a national study of internal medicine residents and faculty. Medical student's reflective written comments were qualitatively assessed. Intervention: Required 32-hour didactic and experiential curriculum, including home hospice visits and inpatient hospice care, with content drawn from the AMA-sponsored Education for Physicians on End-of-life Care (EPEC) Project. Results: Analysis of 487 paired t tests shows significant improvements, with 23% improvement in knowledge (F1,486=881, p<0.001), 56% improvement in self-reported competence (F1,486=2,804, p<0.001), and 29% decrease in self-reported concern (F1,486=208, p<0.001). Retesting medical students in the fourth year showed a further 5% increase in confidence (p<0.0002), 13% increase in allaying concerns (p<0.0001), but a 6% drop in knowledge. The curriculum's effect size on M3 students' knowledge (0.56) exceeded that of a national cross-sectional study comparing residents at progressive training levels (0.18) Themes identified in students' reflective comments included perceived relevance, humanism, and effectiveness of methods used to teach and assess palliative care education. Conclusions: We conclude that required structured didactic and experiential palliative care during the clinical clerkship year of medical student education shows significant and largely sustained effects indicating students are better prepared than a national sample of residents and attending physicians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98455/1/jpm%2E2010%2E0502.pd