46 research outputs found

    The Visibility of Galactic Bars and Spiral Structure At High Redshifts

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    We investigate the visibility of galactic bars and spiral structure in the distant Universe by artificially redshifting 101 B-band CCD images of local spiral galaxies from the Ohio State University Bright Spiral Galaxy Survey. Our artificially redshifted images correspond to Hubble Space Telescope I-band observations of the local galaxy sample seen at z=0.7, with integration times matching those of both the very deep Northern Hubble Deep Field data, and the much shallower Flanking Field observations. The expected visibility of galactic bars is probed in two ways: (1) using traditional visual classification, and (2) by charting the changing shape of the galaxy distribution in "Hubble space", a quantitative two-parameter description of galactic structure that maps closely on to Hubble's original tuning fork. Both analyses suggest that over 2/3 of strongly barred luminous local spirals i.e. objects classified as SB in the Third Reference Catalog) would still be classified as strongly barred at z=0.7 in the Hubble Deep Field data. Under the same conditions, most weakly barred spirals (classified SAB in the Third Reference Catalog) would be classified as regular spirals. The corresponding visibility of spiral structure is assessed visually, by comparing luminosity classifications for the artificially redshifted sample with the corresponding luminosity classifications from the Revised Shapley Ames Catalog. We find that for exposures times similar to that of the Hubble Deep Field spiral structure should be detectable in most luminous low-inclination spiral galaxies at z=0.7 in which it is present. [ABRIDGED]Comment: Accepted for publication in The Astronomical Journa

    Successful staged hip replacement in septic hip osteoarthritis in osteopetrosis: a case report

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    <p>Abstract</p> <p>Background</p> <p>Osteopetrosis is a rare, inherited, bone disorder, characterized by osteosclerosis, obliteration of the medullary cavity and calcified cartilage. The autosomal dominant form is compatible with a normal life span, although fractures often result from minimal trauma, due to the pathologic nature of bone. Osteomyelitis is common in patients with osteopetrosis because of a reduced resistance to infection, attributed to the lack of marrow vascularity and impairment of white cell function. Only one case of osteomyelitis of the proximal third of the femur has been previously reported, treated with several repeated debridements and finally with femoral head resection. Here we present for the first time a case of a staged implant of a cementless total hip prosthesis for the treatment of a septic hip in femoral neck nonunion in osteopetrosis.</p> <p>Case presentation</p> <p>A 36-years-old woman, affected by autosomal dominant osteopetrosis was referred to our department because of a septic hip arthritis associated with femoral neck septic non-union, with draining fistulas. The infection occurred early after a plate osteosynthesis for a closed perthrocanteric fracture of the femur and persisted in spite of osteosynthesis removal, surgical debridement and external fixation. In our hospital the patient underwent accurate debridement, femoral head and greater trochanter resection, preparation of the diaphyseal intramedullary canal and implant of an antibiotic-loaded cement spacer. The spacer was exchanged after one month, due to infection recurrence and four months later, a cementless total hip arthroplasty was implanted, with no clinical and laboratory signs of infection recurrence at two years follow-up.</p> <p>Conclusions</p> <p>In case of hip septic arthritis and proximal femur septic non-union, femoral head resection may not be the only option available and staged total hip arthroplasty can be considered.</p

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

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    Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

    Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

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    The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

    'I wouldn't have been interested in just sitting round a table talking about cancer'; exploring the experiences of women with breast cancer in a group exercise trial

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    There is evidence that physical activity improves the psychological and physical health of patients with cancer. However, relatively little attention has been paid to understanding their experiences of exercise. This focus group study explored the experiences of women undergoing treatment for breast cancer who had taken part in a supervised group exercise trial. We found that setting up classes solely for women with breast cancer, led by an expert instructor, helped to reduce gender-related barriers to physical activity, such as difficulties in prioritizing exercise over caring roles and worries about changed appearance. For example, some women challenged traditional expectations of femininity by removing their wigs in the classes in order to exercise in comfort. Respondents valued exercising with women in the 'same boat' because of the empathy and acceptance they received and the opportunities to exchange information and form friendships. However, the action-orientated format of the group was preferred to a talk-based format such as a support group; some respondents felt that the 'last thing' they wished to do was to talk about cancer. Our findings therefore challenge stereotypes about women invariably preferring to cope with cancer through emotional disclosure

    The prescriber's guide to classic MAO-inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression

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    This article is a clinical guide which discusses the state-of-The-Art usage of the classic MAOI antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI-prescribers. It discusses indications, drug drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (over 70 international expert129 endorsers), based on six decades of experience, for the recommendations herein exposited. They are based on empirical evidence and on expert opinion this guide is presented as a new specialist131 consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to ECT whilst taking account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some TCAs. It also illustrates the straightforward bridging methods that may be used to transition simply and safely from other antidepressants to MAOIs
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