XMM–Newton campaign on ultraluminous X-ray source NGC 1313 X-1: wind versus state variability

Most ultraluminous X-ray sources (ULXs) are thought to be powered by neutron stars and black holes accreting beyond the Eddington limit. If the compact object is a black hole or a neutron star with a magnetic field ≲1012 G, the accretion disc is expected to thicken and launch powerful winds driven by radiation pressure. Evidence of such winds has been found in ULXs through the high-resolution spectrometers onboardXMM–Newton, but several unknowns remain, such as the geometry and launching mechanism of these winds. In order to better understand ULX winds and their link to the accretion regime, we have undertaken a major campaign with XMM–Newton to study the ULX NGC 1313 X-1, which is known to exhibit strong emission and absorption features from a mildly relativistic wind. The new observations show clear changes in the wind with a significantly weakened fast component (0.2c) and the rise of a new wind phase which is cooler and slower (0.06–0.08c). We also detect for the first time variability in the emission lines which indicates an origin within the accretion disc or in the wind. We describe the variability of the wind in the framework of variable super-Eddington accretion rate and discuss a possible geometry for the accretion disc

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Treatment of osteoporosis in an older home care population

BACKGROUND: Previous research indicates that many patients with fractures indicative of underlying osteoporosis are not receiving appropriate diagnostic follow-up and therapy. We assessed osteoporosis treatment coverage in older home care clients with a diagnosis of osteoporosis and/or prevalent fracture. METHODS: Subjects included 330 home care clients, aged 65+, participating in a longitudinal study of medication adherence and health-related outcomes. Data on clients' demographic, health and functional status and service utilization patterns were collected using the Minimum Data Set for Home Care (MDS-HC). A medication review included prescribed and over-the-counter medications taken in the past 7 days. Criteria for indications for osteoporosis therapy included diagnosis of osteoporosis or a recent fracture. Coverage for treatment was examined for anti-osteoporotic therapies approved for use in 2000. RESULTS: Of the 330 home care clients, 78 (24%) had a diagnosis of osteoporosis (n = 47) and/or had sustained a recent fracture (n = 34). Drug data were available for 77/78 subjects. Among the subjects with osteoporosis or a recent fracture, 45.5% were receiving treatment for osteoporosis; 14% were receiving only calcium and vitamin D, and an additional 31% were receiving drug therapy (bisphosphonate or hormone replacement therapy). The remaining 54.5% of subjects were not receiving any approved osteoporosis therapy. CONCLUSIONS: The high prevalence of undertreatment among a population of older adults with relatively high access to health care services raises concern regarding the adequacy of diagnosis and treatment of osteoporosis in the community

Orbital Decay in M82 X-2

M82 X-2 is the first pulsating ultraluminous X-ray source discovered. The luminosity of these extreme pulsars, if isotropic, implies an extreme mass transfer rate. An alternative is to assume a much lower mass transfer rate, but with an apparent luminosity boosted by geometrical beaming. Only an independent measurement of the mass transfer rate can help discriminate between these two scenarios. In this paper, we follow the orbit of the neutron star for 7 yr, measure the decay of the orbit ((P) over dot(orb)/(P) over dot(orb) approximate to -8.10(-6) yr(-1)), and argue that this orbital decay is driven by extreme mass transfer of more than 150 times the mass transfer limit set by the Eddington luminosity. If this is true, the mass available to the accretor is more than enough to justify its luminosity, with no need for beaming. This also strongly favors models where the accretor is a highly magnetized neutron star

Knowledge and awareness of the general public and perception of pharmacists about antibiotic resistance

Background Antibiotic resistance (AR) continues to be a serious problem. Many factors contribute to AR, including inappropriate use of antibiotics, in which both healthcare professionals and patients play a contributing role. This study aimed to assess the awareness and knowledge of antibiotic usage and AR among the general public (in affluent and deprived areas) and community pharmacists' (CPs') in Greater London. Methods A cross-sectional survey involving members of the public was conducted between July 2014 and February 2015. Stage one involved members of the public (N = 384) residing in affluent areas of London. The second stage targeted public (N = 384) in deprived areas of London. In addition, CPs (N = 240) across the same areas were also surveyed. Data analysis was performed using Microsoft Excel and SPSS Software packages. Results Response rate: 36% (n = 139/384) and 57% (n = 220/384) and 25% (n = 60/240) of public residing in affluent areas, deprived areas and of CPs respectively was achieved. Definitive trends in knowledge of how antibiotics work could not be drawn to distinguish between affluent and deprived areas. However, public respondents residing in affluent areas possessed better understanding of AR and prudent use of antibiotics, and this was statistically significant in both cases (p < 0.05). Exposure to an antibiotic campaign (32% in affluent areas, 17% in deprived areas) did not raise public respondents' knowledge on AR and only partially raised their general knowledge on antibiotics usage. Only 20% of public residing in deprived areas received counselling from a CP, among them 74% had an antibiotic prescribed on at least one previous occasion. Those who received counselling displayed better knowledge about concordance/adherence with respect to antibiotic usage (p < 0.05) whereas exposure to an antibiotic campaign made no significant impact on knowledge about concordance/adherence. Conclusion The study highlights that there has been no change in the status quo with respect to awareness of antibiotic usage and AR even after the implementation of several awareness campaigns in England. Those who benefited from CP counselling showed a significant better knowledge towards prudent antibiotic usage which stresses the importance of CPs' counselling on antibiotic prescription

Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

The deposited item is a book chapter and is part of the series "Centromeres and Kinetochores" published by the publisher Springer Verlag. The deposited book chapter is a post-print version and has been submitted to peer reviewing. There is no public supplementary material available for this publication. This publication hasn't any creative commons license associated.Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication. These features come together to maintain homeostasis of a chromatin locus that directs its own epigenetic inheritance and facilitates the assembly of the mitotic kinetochore.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio