Hydrogen-poor superluminous stellar explosions

Supernovae (SNe) are stellar explosions driven by gravitational or thermonuclear energy, observed as electromagnetic radiation emitted over weeks or more. In all known SNe, this radiation comes from internal energy deposited in the outflowing ejecta by either radioactive decay of freshly-synthesized elements (typically 56Ni), stored heat deposited by the explosion shock in the envelope of a supergiant star, or interaction between the SN debris and slowly-moving, hydrogen-rich circumstellar material. Here we report on a new class of luminous SNe whose observed properties cannot be explained by any of these known processes. These include four new SNe we have discovered, and two previously unexplained events (SN 2005ap; SCP 06F6) that we can now identify as members. These SNe are all ~10 times brighter than SNe Ia, do not show any trace of hydrogen, emit significant ultra-violet (UV) flux for extended periods of time, and have late-time decay rates which are inconsistent with radioactivity. Our data require that the observed radiation is emitted by hydrogen-free material distributed over a large radius (~10^15 cm) and expanding at high velocities (>10^4 km s^-1). These long-lived, UV-luminous events can be observed out to redshifts z>4 and offer an excellent opportunity to study star formation in, and the interstellar medium of, primitive distant galaxies.Comment: Accepted to Nature. Press embargoed until 2011 June 8, 18:00 U

Trends in long-term opioid prescribing in primary care patients with musculoskeletal conditions: an observational database study

Long-term opioids may benefit patients with chronic pain but have also been linked to harmful outcomes. In the United Kingdom, the predominant source of opioids is primary care prescription. The objective was to examine changes in the incidence, length, and opioid potency of long-term prescribing episodes for musculoskeletal conditions in UK primary care (2002-2013). This was an observational database study (Clinical Practice Research Datalink, 190 practices). Participants (≥18 years) were prescribed an opioid for a musculoskeletal condition (no opioid prescribed in previous 6 months), and issued ≥2 opioid prescriptions within 90 days (long-term episode). Opioids were divided into short- and long-acting noncontrolled and controlled drugs. Annual incidence of long-term opioid episodes was determined, and for those still in a long-term episode, the percentage of patients prescribed each type 1 to 2 years, and >2 years after initiation. Annual denominator population varied from 1.25 to 1.38 m. A total of 76,416 patients started 1 long-term episode. Annual long-term episode incidence increased (2002-2009) by 38% (42.4-58.3 per 10,000 person-years), remaining stable to 2011, then decreasing slightly to 55.8/10,000 (2013). Patients prescribed long-acting controlled opioids within the first 90 days of long-term use increased from 2002 to 2013 (2.3%-9.9%). In those still in a long-term opioid episode (>2 years), long-acting controlled opioid prescribing increased from 3.5% to 22.6%. This study has uniquely shown an increase in prescribing long-term opioids to 2009, gradually decreasing from 2011 in the United Kingdom. The trend was towards increased prescribing of controlled long-acting opioids and earlier use. Further research into the risks and benefits of opioids is required

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

Rethinking drug design in the artificial intelligence era

Artificial intelligence (AI) tools are increasingly being applied in drug discovery. While some protagonists point to vast opportunities potentially offered by such tools, others remain sceptical, waiting for a clear impact to be shown in drug discovery projects. The reality is probably somewhere in-between these extremes, yet it is clear that AI is providing new challenges not only for the scientists involved but also for the biopharma industry and its established processes for discovering and developing new medicines. This article presents the views of a diverse group of international experts on the 'grand challenges' in small-molecule drug discovery with AI and the approaches to address them

A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

The influence of farmers' mental models on an agroforestry extension program in the Philippines

The influence of farmers' mental models on the success of an agroforestry extension program on Leyte Island in the Philippines was investigated. Knowledge of farmers' mental models and hence the likely acceptance of technology was used to inform the design of a hypothetically expanded program. To gain an insight into the reasons behind differing acceptance of extension assistance, data were collected and analysed from formal interviews, translated conversations and visual observations. The data provided a chain of evidence and triangulation between farmers' stated intentions and their actions. Farmers had little prior knowledge of nursery technology and were highly receptive to extension assistance which enabled them to develop high self-efficacy in seedling production. However, farmers' rejection of silvicultural advice to thin and prune existing plantations was predicated by existing attitudes to forest resource management. Farmers also expressed a strong preference for a low-cost and low-input approach to establishing timber trees. Visual observations of farmers' tree establishment practices indicated the existence of gaps in their knowledge of tree growth processes. This investigation illustrates the need to elicit farmers' mental models as a parallel enquiry to extension activities. If agroforestry extension is to be constructivist and participatory, accommodation of farmers' mental models and modification of program goals may be necessary. Relatively little is known about the reasons for farmers' acceptance or rejection of silviculture in Leyte and these results indicate that further research into the way that farmers' mental models filter and guide acceptance of advice may be worthwhile

An interdisciplinary intervention for older Taiwanese patients after surgery for hip fracture improves health-related quality of life

Abstract Background The effects of intervention programs on health-related quality of life (HRQOL) of patients with hip fracture have not been well studied. We hypothesized that older patients with hip fracture who received our interdisciplinary intervention program would have better HRQOL than those who did not. Methods A randomized experimental design was used. Older patients with hip fracture (N = 162), 60 to 98 years old, from a medical center in northern Taiwan were randomly assigned to an experimental (n = 80) or control (n = 82) group. HRQOL was measured by the SF-36 Taiwan version at 1, 3, 6, and 12 months after discharge. Results The experimental group had significantly better overall outcomes in bodily pain (β = 9.38, p = 0.002), vitality (β = 9.40, p < 0.001), mental health (β = 8.16, p = 0.004), physical function (β = 16.01, p < 0.001), and role physical (β = 22.66, p < 0.001) than the control group at any time point during the first year after discharge. Physical-related health outcomes (physical functioning, role physical, and vitality) had larger treatment effects than emotional/mental- and social functioning-related health outcomes. Conclusions This interdisciplinary intervention program may improve health outcomes of elders with hip fracture. Our results may provide a reference for health care providers in countries using similar programs with Chinese/Taiwanese immigrant populations. Trial registration NCT01052636http://deepblue.lib.umich.edu/bitstream/2027.42/78259/1/1471-2474-11-225.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78259/2/1471-2474-11-225.pdfPeer Reviewe

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

No exit from the euro-rescuing trap?

This paper attempts a normative assessment of the input and output-oriented legitimacy of the present euro-rescuing regime on the basis of policy analyses examining the causes of present crises, the available policy options, and the impact of the policies actually chosen. Concluding that the regime lacks input-oriented legitimacy and that its claim to output-oriented legitimacy is ambivalent at best, the paper explores potential – majoritarian or unilateral – exits from the present institutional constellation that is characterized by the synthesis of a non-democratic expertocracy and an extremely asymmetric intergovernmental bargaining system.Die hier präsentierte normative Bewertung der input- und outputorientierten Legitimität des gegenwärtigen Euro-Rettungs-Regimes stützt sich auf empirisch fundierte Aussagen zu den Ursachen der Eurokrise, den prinzipiell verfügbaren Politik-Optionen und den Wirkungen der gewählten Politik. Im Ergebnis wird eine inputorientierte Legitimation verneint, während die outputorientierte Bewertung höchst ambivalent erscheint. Im Schlussteil untersucht der Text mögliche – majoritäre oder einseitige – Auswege aus einer institutionellen Konstellation, die ein nicht demokratisches Expertenregime mit inem extrem asymmetrischen intergouvernementalen Verhandlungsregime verbindet