Magnetar-like X-ray Bursts from an Anomalous X-ray Pulsar

Anomalous X-ray Pulsars (AXPs) are a class of rare X-ray pulsars whose energy source has been perplexing for some 20 years. Unlike other, better understood X-ray pulsars, AXPs cannot be powered by rotation or by accretion from a binary companion, hence the designation ``anomalous.'' AXP rotational and radiative properties are strikingly similar to those of another class of exotic objects, the Soft Gamma Repeaters (SGRs). However, the defining property of SGRs, namely their low-energy gamma-ray and X-ray bursts, have heretofore not been seen in AXPs. SGRs are thought to be ``magnetars,'' young neutron stars powered by the decay of an ultra-high magnetic field. The suggestion that AXPs are magnetars has been controversial. Here we report the discovery, from the direction of AXP 1E 1048-5937, of two X-ray bursts that have many properties similar to those of SGR bursts. These events imply a close relationship between AXPs and SGRs, with both being magnetars.Comment: 14 pages, 2 figures, accepted for publication in Nature. Note: The content of this paper is embargoed until 1900 hrs London time / 1400 US Eastern Time on Sept 1

The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

Swings between rotation and accretion power in a millisecond binary pulsar

It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods. During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar whose emission is powered by the neutron star's rotating magnetic field. This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars and also by the evidence for a past accretion disc in a rotation-powered millisecond pulsar. It has been proposed that a rotation-powered pulsar may temporarily switch on during periods of low mass inflow in some such systems. Only indirect evidence for this transition has hitherto been observed. Here we report observations of accretion-powered, millisecond X-ray pulsations from a neutron star previously seen as a rotation-powered radio pulsar. Within a few days after a month-long X-ray outburst, radio pulses were again detected. This not only shows the evolutionary link between accretion and rotation-powered millisecond pulsars, but also that some systems can swing between the two states on very short timescales.Comment: 43 pages, 9 figures, 4 table. Published by Nature on 26 Sep 2013. Includes Supplementary information. Minor differences with published version may exis

Thirty years after Alma-Ata: a systematic review of the impact of community health workers delivering curative interventions against malaria, pneumonia and diarrhoea on child mortality and morbidity in sub-Saharan Africa

BACKGROUND: Over thirty years have passed since the Alma-Ata Declaration on primary health care in 1978. Many governments in the first decade following the declaration responded by developing national programmes of community health workers (CHWs), but evaluations of these often demonstrated poor outcomes. As many CHW programmes have responded to the HIV/AIDS pandemic, international interest in them has returned and their role in the response to other diseases should be examined carefully so that lessons can be applied to their new roles. Over half of the deaths in African children under five years of age are due to malaria, diarrhoea and pneumonia - a situation which could be addressed through the use of cheap and effective interventions delivered by CHWs. However, to date there is very little evidence from randomised controlled trials of the impacts of CHW programmes on child mortality in Africa. Evidence from non-randomised controlled studies has not previously been reviewed systematically. METHODS: We searched databases of published and unpublished studies for RCTs and non-randomised studies evaluating CHW programmes delivering curative treatments, with or without preventive components, for malaria, diarrhoea or pneumonia, in children in sub-Saharan Africa from 1987 to 2007. The impact of these programmes on morbidity or mortality in children under six years of age was reviewed. A descriptive analysis of interventional and contextual factors associated with these impacts was attempted. RESULTS: The review identified seven studies evaluating CHWs, delivering a range of interventions. Limited descriptive data on programmes, contexts or process outcomes for these CHW programmes were available. CHWs in national programmes achieved large mortality reductions of 63% and 36% respectively, when insecticide-treated nets and anti-malarial chemoprophylaxis were delivered, in addition to curative interventions. CONCLUSIONS: CHW programmes could potentially achieve large gains in child survival in sub-Saharan Africa if these programmes were implemented at scale. Large-scale rigorous studies, including RCTs, are urgently needed to provide policymakers with more evidence on the effects of CHWs delivering these interventions

Pharmacokinetics of Teriparatide (rhPTH[1–34]) and Calcium Pharmacodynamics in Postmenopausal Women with Osteoporosis

Teriparatide (rhPTH[1–34]) affects calcium metabolism in a pattern consistent with the known actions of endogenous parathyroid hormone (PTH). This report describes the pharmacokinetics and resulting serum calcium response to teriparatide in postmenopausal women with osteoporosis. Pharmacokinetic samples for this analysis were obtained from 360 women who participated in the Fracture Prevention Trial. Postmenopausal women with osteoporosis received daily subcutaneous injections of either teriparatide 20 μg (4.86 μmol) or placebo, median 21 months’ treatment. Serum teriparatide and calcium concentrations were measured throughout the study. An indirect-response model was developed to describe the pharmacokinetic–pharmacodynamic relationship between teriparatide concentrations and serum calcium response. The pharmacokinetics of teriparatide were characterized by rapid absorption (maximum concentration achieved within 30 min) and rapid elimination (half-life of 1 h), resulting in a total duration of exposure to the peptide of approximately 4 h. Teriparatide transiently increased serum calcium, with the maximum effect observed at approximately 4.25 h (median increase 0.4 mg/dl [0.1 mmol/l]). Calcium concentrations returned to predose levels by 16–24 h after each dose. Persistent hypercalcemia was not observed; one teriparatide 20 μg-treated patient had a predose serum calcium value above the normal range but <11.0 mg/dl (2.75 mmol/l). Following once-daily subcutaneous administration, teriparatide produces a modest but transient increase in serum calcium, consistent with the known effects of endogenous PTH on mineral metabolism. The excursion in serum calcium is brief, due to the short length of time that teriparatide concentrations are elevated

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. Methods: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 + T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 + T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. Results: All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. Conclusions: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes

Rhodopsin Mutant P23H Destabilizes Rod Photoreceptor Disk Membranes

Mutations in rhodopsin cause retinitis pigmentosa in humans and retinal degeneration in a multitude of other animals. We utilized high-resolution live imaging of the large rod photoreceptors from transgenic frogs (Xenopus) to compare the properties of fluorescently tagged rhodopsin, Rho-EGFP, and RhoP23H-EGFP. The mutant was abnormally distributed both in the inner and outer segments (OS), accumulating in the OS to a concentration of ∼0.1% compared to endogenous opsin. RhoP23H-EGFP formed dense fluorescent foci, with concentrations of mutant protein up to ten times higher than other regions. Wild-type transgenic Rho-EGFP did not concentrate in OS foci when co-expressed in the same rod with RhoP23H-EGFP. Outer segment regions containing fluorescent foci were refractory to fluorescence recovery after photobleaching, while foci in the inner segment exhibited recovery kinetics similar to OS regions without foci and Rho-EGFP. The RhoP23H-EGFP foci were often in older, more distal OS disks. Electron micrographs of OS revealed abnormal disk membranes, with the regular disk bilayers broken into vesiculotubular structures. Furthermore, we observed similar OS disturbances in transgenic mice expressing RhoP23H, suggesting such structures are a general consequence of mutant expression. Together these results show that mutant opsin disrupts OS disks, destabilizing the outer segment possibly via the formation of aggregates. This may render rods susceptible to mechanical injury or compromise OS function, contributing to photoreceptor loss

Covert Genetic Selections to Optimize Phenotypes

In many high complexity systems (cells, organisms, institutions, societies, economies, etc.), it is unclear which components should be regulated to affect overall performance. To identify and prioritize molecular targets which impact cellular phenotypes, we have developed a selection procedure (“SPI”–single promoting/inhibiting target identification) which monitors the abundance of ectopic cDNAs. We have used this approach to identify growth regulators. For this purpose, complex pools of S. cerevisiae cDNA transformants were established and we quantitated the evolution of the spectrum of cDNAs which was initially present. These data emphasized the importance of translation initiation and ER-Golgi traffic for growth. SPI provides functional insight into the stability of cellular phenotypes under circumstances in which established genetic approaches cannot be implemented. It provides a functional “synthetic genetic signature” for each state of the cell (i.e. genotype and environment) by surveying complex genetic libraries, and does not require specialized arrays of cDNAs/shRNAs, deletion strains, direct assessment of clonal growth or even a conditional phenotype. Moreover, it establishes a hierarchy of importance of those targets which can contribute, either positively or negatively, to modify the prevailing phenotype. Extensions of these proof-of-principle experiments to other cell types should provide a novel and powerful approach to analyze multiple aspects of the basic biology of yeast and animal cells as well as clinically-relevant issues

Meat consumption and risk of breast cancer in the UK Women's Cohort Study

We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer