Ion Charge States in Halo CMEs: What can we Learn about the Explosion?

We describe a new modeling approach to develop a more quantitative understanding of the charge state distributions of the ions of various elements detected in situ during halo Coronal Mass Ejection (CME) events by the Advanced Composition Explorer (ACE) satellite. Using a model CME hydrodynamic evolution based on observations of CMEs propagating in the plane of the sky and on theoretical models, we integrate time dependent equations for the ionization balance of various elements to compare with ACE data. We find that plasma in the CME ``core'' typically requires further heating following filament eruption, with thermal energy input similar to the kinetic energy input. This extra heating is presumably the result of post eruptive reconnection. Plasma corresponding to the CME ``cavity'' is usually not further ionized, since whether heated or not, the low density gives freeze-in close the the Sun. The current analysis is limited by ambiguities in the underlying model CME evolution. Such methods are likely to reach their full potential when applied to data to be acquired by STEREO when at optimum separation. CME evolution observed with one spacecraft may be used to interpret CME charge states detected by the other.Comment: 20 pages, accepted by Ap

The Risk of Venous Thromboembolism (VTE) in Men with Benign Prostatic Hyperplasia Treated with 5-Alpha Reductase Inhibitors (5ARIs)

Background: Many men receive 5-alpha reductase inhibitors (5ARIs) for ongoing treatment of benign prostatic hyperplasia (BPH). The increased risk of cardiovascular complications with 5ARIs has been documented in BPH studies and the occurrence of cerebral venous thrombosis, presumably due to increased estrogen level following 5ARI use, was described in multiple case reports. The objective of this study was to determine if 5ARIs with or without alpha blockers (AB) were associated with an increased risk of venous thromboembolism (VTE) in males with BPH. Methods: We conducted a nested case-control study among a population of men ages 40-79 who received at least one 5ARI or AB prescription for treatment of BPH between 1995 and 2015 in the UK-based Clinical Practice Research Datalink GOLD. Cases of incident VTE (pulmonary embolism [PE] or deep venous thrombosis [DVT]) and matched controls were identified from this population. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE in users of 5ARIs compared to users of ABs. Results: For 5ARI only users, the adjusted odds ratios (aORs), (95% CI) for VTE were 1.51 (0.98-2.32) in current 5ARI users and 1.23 (0.70-2.17) in recent/distant past, compared to AB only users. However, the aOR (95% CI) in men who had 50 or more current 5ARI prescriptions compared to users of ABs only was higher: 2.29 (1.14-4.63). For 5ARI with AB use, the aORs, (95% CI) for VTE were 1.16 (0.64-2.10) in current 5ARI+AB users and 1.93 (0.71-5.25) in recent/distant past, compared to AB only users. The aOR (95% CI) in men who had 50 or more current 5ARI+AB prescriptions compared to users of ABs only was 1.65 (0.64-4.26). Conclusion: Current use of 5ARI, particularly long-term use, is associated with an increased risk of incident idiopathic VTE compared to patients treated with AB use only

Time Course of Recruitment, Pit Formation and Apoptosis of Osteoclast Populations on Dentin In Vitro

The resorptive capacity of osteoclasts in vitro has been used as an indicator of bone resorption. However, the kinetics of osteoclast development and senescence is not well understood. It has been noted that mononuclear precursors migrate to calcified substrate and after multi-nucleation become competent bone resorbing cells. Osteoclasts, once finished a wave of resorption, become senescent. In order to determine the survival characteristics of osteoclast populations involved in calcified tissue destruction, we have investigated the time course of the recruitment to dentin and apoptosis of osteoclasts. We have established the linkage between these measurements and the time course of the appearance of pits using both chick and rat osteoclasts in vitro. Osteoclasts from both species caused increases in pit number associated with decreases in cell number on dentin. In the rat model, we have used a fluorescent linker to mark cells before they migrate to dentin and have shown that cells can be followed from the culture dish onto the dentin disc. In the chick model, we have used time lapse cinematography and fluorescent nuclear staining to observe death of osteoclasts on dentin and have established an osteoclast half live in vitro

Altered protein dynamics of disease-associated lamin A mutants

BACKGROUND: Recent interest in the function of the nuclear lamina has been provoked by the discovery of lamin A/C mutations in the laminopathy diseases. However, it is not understood why mutations in lamin A give such a range of tissue-specific phenotypes. Part of the problem in rationalising genotype-phenotype correlations in the laminopathies is our lack of understanding of the function of normal and mutant lamin A. To investigate this we have used photobleaching in human cells to analyse the dynamics of wild-type and mutant lamin A protein at the nuclear periphery. RESULTS: We have found that a large proportion of wild-type lamin A at the nuclear periphery is immobile, but that there is some slow movement of lamin A within the nuclear lamina. The mobility of an R482W mutant lamin A was indistinguishable from wild-type, but increased mobility of L85R and L530P mutant proteins within the nuclear lamina was found. However, the N195K mutant shows the most enhanced protein mobility, both within the nucleoplasm and within the lamina. CONCLUSION: The slow kinetics of lamin A movement is compatible with its incorporation into a stable polymer that only exchanges subunits very slowly. All of the myopathy-associated lamin A mutants that we have studied show increased protein movement compared with wild-type. In contrast, the dynamic behaviour of the lipodystrophy-associated lamin A mutant was indistinguishable from wild-type. This supports the hypothesis that the underlying defect in lamin A function is quite distinct in the laminopathies that affect striated muscle, compared to the diseases that affect adipose tissue. Our data are consistent with an alteration in the stability of the lamin A molecules within the higher-order polymer at the nuclear lamina in myopathies

Post-discharge care following acute kidney injury: quality improvement in primary care

BACKGROUND: Over the past decade, targeting acute kidney injury (AKI) has become a priority to improve patient safety and health outcomes. Illness complicated by AKI is common and is associated with adverse outcomes including high rates of unplanned hospital readmission. Through national patient safety directives, NHS England has mandated the implementation of an AKI clinical decision support system in hospitals. In order to improve care following AKI, hospitals have also been incentivised to improve discharge summaries and general practices are recommended to establish registers of people who have had an episode of illness complicated by AKI. However, to date, there is limited evidence surrounding the development and impact of interventions following AKI. DESIGN: We conducted a quality improvement project in primary care aiming to improve the management of patients following an episode of hospital care complicated by AKI. All 31 general practices within a single NHS Clinical Commissioning Group were incentivised by a locally commissioned service to engage in audit and feedback, education training and to develop an action plan at each practice to improve management of AKI. RESULTS: AKI coding in general practice increased from 28% of cases in 2015/2016 to 50% in 2017/2018. Coding of AKI was associated with significant improvements in downstream patient management in terms of conducting a medication review within 1 month of hospital discharge, monitoring kidney function within 3 months and providing written information about AKI to patients. However, there was no effect on unplanned hospitalisation and mortality. CONCLUSION: The findings suggest that the quality improvement intervention successfully engaged a primary care workforce in AKI-related care, but that a higher intensity intervention is likely to be required to improve health outcomes. Development of a real-time audit tool is necessary to better understand and minimise the impact of the high mortality rate following AKI

A 43-Nucleotide RNACis-Acting Element Governs the Site-Specific Formation of the 3′ End of a Poxvirus Late mRNA

AbstractThe 3′ ends of late mRNAs of theatigene, encoding the major component of the A-type inclusions, are generated by endoribonucleolytic cleavage at a specific site in the primary transcript [Antczaket al.,(1992),Proc. Natl. Acad. Sci. USA89, 12033–12037]. In this study, sequence analysis of cDNAs of the 3′ ends ofatimRNAs showed these mRNAs are 3′ polyadenylated at the RNA cleavage site. This suggests thatatimRNA 3′ end formation involves cleavage of a late transcript, with subsequent 3′ polyadenylation of the 5′ cleavage product. The RNAcis-acting element, the AX element, directing orientation-dependent formation of these mRNA 3′ ends, was mapped to a 345-bpAluI–XbaI fragment. Deletion analyses of this fragment showed that the boundaries of the AX element are within −5 and +38 of the RNA cleavage site. Scanning mutagenesis showed that the AX element contains at least two subelements: subelement I, 5′-UUUAU↓CCGAUAAUUC-3′, containing the cleavage site (↓), separated from the downstream subelement II, 5′-AAUUUCGGAUUUGAAUGC-3′, by a 10-nucleotide region, whose composition may be altered without effect on RNA 3′ end formation. These features, which differ from those of other elements controlling RNA processing, suggest that the AX element is a component of a novel mechanism of RNA 3′ end formation

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

More that unites us than divides us? A qualitative study of integration of community health and social care services

From Springer Nature via Jisc Publications RouterHistory: received 2019-09-13, accepted 2020-05-17, registration 2020-05-18, pub-electronic 2020-05-29, online 2020-05-29, collection 2020-12Publication status: PublishedFunder: Collaboration for Leadership in Applied Health Research and Care - Greater Manchester; doi: http://dx.doi.org/10.13039/501100012358; Grant(s): NAAbstract: Background: The integration of community health and social care services has been widely promoted nationally as a vital step to improve patient centred care, reduce costs, reduce admissions to hospital and facilitate timely and effective discharge from hospital. The complexities of integration raise questions about the practical challenges of integrating health and care given embedded professional and organisational boundaries in both sectors. We describe how an English city created a single, integrated care partnership, to integrate community health and social care services. This led to the development of 12 integrated neighbourhood teams, combining and co-locating professionals across three separate localities. The aim of this research is to identify the context and the factors enabling and hindering integration from a qualitative process evaluation. Methods: Twenty-four semi-structured interviews were conducted with equal numbers of health and social care staff at strategic and operational level. The data was subjected to thematic analysis. Results: We describe three key themes: 1) shared vision and leadership; 2) organisational factors; 3) professional workforce factors. We found a clarity of vision and purpose of integration throughout the partnership, but there were challenges related to the introduction of devolved leadership. There were widespread concerns that the specified outcome measures did not capture the complexities of integration. Organisational challenges included a lack of detail around clinical and service delivery planning, tensions around variable human resource practices and barriers to data sharing. A lack of understanding and trust meant professional workforce integration remained a key challenge, although integration was also seen as a potential solution to engender relationship building. Conclusions: Given the long-term national policy focus on integration this ambitious approach to integrate community health and social care has highlighted implications for leadership, organisational design and inter-professional working. Given the ethos of valuing the local assets of individuals and networks within the new partnership we found the integrated neighbourhood teams could all learn from each other. Many of the challenges of integration could benefit from embracing the inherent capabilities across the integrated neighbourhood teams and localities of this city

Anatomy of an oil spill : long-term effects from the grounding of the barge Florida off West Falmouth, Massachusetts

Author Posting. © Yale University, 1980. This article is posted here by permission of Yale University for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 38 (1980): 265-380.To determine carefully the effects on the marine and estuarine benthos of Number 2 fuel oil spilled by the barge FLORIDA off West Falmouth, Massachusetts, we sampled for many months along an onshore-offshore gradient of pollution, and less intensively at unoiled sites. Analyses of hydrocarbons established that pollution was greatest and most persistent in the intertidal and subtidal zones of Wild Harbor River, less severe in degree and duration at stations farthest from shore. A variety of concurrent analyses showed that disturbance of the fauna was most severe and longest lasting at the most heavily oiled sites, and least severe but perceptible at lightly oiled stations. Patterns of disturbance were not related to granulometry of the sediments. Plants, ctustaceans, fish, and birds suffered both high mortality immediately after the spill, and physiological and behavioral abnormalities directly related to high concentrations of the fuel oil. Five years after the spill its effects on the biota were still detectable, and partly degraded #2 fuel oil was still present in the sediments in Wild Harbor River and estuary.Our study was partially supported by the Federal Water Pollution Control Contract 15080, the Environmental Protection Agency Grant No. R80100102 and Massachusetts Division of Water Pollution Control primarily during the initial three years and by the Woods Hole Oceanographic Institution at specific key periods