Anti-coagulation, anti-platelets or no therapy in haemodialysis patients with atrial fibrillation: a decision analysis

BACKGROUND: Optimal treatment of atrial fibrillation (AF) in the haemodialysis population is uncertain due to the exclusion of this group from randomized trials. The risk-benefit profile for anticoagulation and anti-platelet therapy in haemodialysis differs from the general population due to platelet dysfunction from uraemia, altered pharmacokinetics and increased falls risk. METHODS: This decision analysis used a Markov-state transition model that took a patient perspective over a 5 year timeframe. The Markov model compared life-years gained and quality-adjusted life-years gained (QALY) for three AF treatment strategies: warfarin, aspirin and no treatment. The base case was a 70-year-old man on haemodialysis with non-valvular AF. RESULTS: In the base case, the total health outcomes in life-years and QALY were 2.37 and 1.47 respectively for warfarin, 2.38 and 1.61 respectively for aspirin, and 2.39 and 1.61 respectively for no treatment. Thus, warfarin led to 0.14 fewer QALY or 1.7 fewer months of life lived in full health, compared with either aspirin or no therapy. The finding that warfarin generated the lowest expected QALY was robust to one-way, two-way and probabilistic sensitivity analyses. CONCLUSIONS: Our results suggest that warfarin should not be the default choice for older haemodialysis patients with non-valvular AF as it provides the fewest QALY compared with aspirin or no therapy

Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.

In this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued

Will Spin-Relaxation Times in Molecular Magnets Permit Quantum Information Processing?

Using X-band pulsed electron-spin resonance, we report the intrinsic spin-lattice (T1) and phase-coherence (T2) relaxation times in molecular nanomagnets for the first time. In Cr7M heterometallic wheels, with M=Ni and Mn, phase-coherence relaxation is dominated by the coupling of the electron spin to protons within the molecule. In deuterated samples T2 reaches 3  μs at low temperatures, which is several orders of magnitude longer than the duration of spin manipulations, satisfying a prerequisite for the deployment of molecular nanomagnets in quantum information applications

GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank

Age-related hearing impairment (ARHI) is the most common sensory impairment in the aging population; a third of individuals are affected by disabling hearing loss by the age of 65. It causes social isolation and depression and has recently been identified as a risk factor for dementia. The genetic risk factors and underlying pathology of ARHI are largely unknown, meaning that targets for new therapies remain elusive, yet heritability estimates range between 35% and 55%. We performed genome-wide association studies (GWASs) for two self-reported hearing phenotypes, using more than 250,000 UK Biobank (UKBB) volunteers aged between 40 and 69 years. Forty-four independent genome-wide significant loci (p < 5E−08) were identified, considerably increasing the number of established trait loci. Thirty-four loci are novel associations with hearing loss of any form, and only one of the ten known hearing loci has a previously reported association with an ARHI-related trait. Gene sets from these loci are enriched in auditory processes such as synaptic activities, nervous system processes, inner ear morphology, and cognition, while genetic correlation analysis revealed strong positive correlations with multiple personality and psychological traits for the first time. Immunohistochemistry for protein localization in adult mouse cochlea implicate metabolic, sensory, and neuronal functions for NID2, CLRN2, and ARHGEF28. These results provide insight into the genetic landscape underlying ARHI, opening up novel therapeutic targets for further investigation. In a wider context, our study also highlights the viability of using self-report phenotypes for genetic discovery in very large samples when deep phenotyping is unavailable

Supportive care in the management of patients with acute myeloid leukaemia: where are the research needs?

Supportive care for patients with acute myeloid leukaemia (AML) is defined as a broad range of interventions that ameliorate the symptoms of a disease, or the side effects caused by treatment, and which address psychological, cultural, social and spiritual factors.1 Transfusion support and infection management are key examples of supportive care that have contributed significantly to the successes of more intensive chemotherapy, delivering improvements in outcomes despite, arguably, only modest improvements in chemotherapy regimens.2 This article will review our current practice of transfusion therapy and infection management and identify research opportunities which the National Cancer Research Institute (NCRI) AML working party are supporting, alongside forthcoming national AML trials

Cost-effectiveness analysis of PET/CT surveillance imaging to detect systemic recurrence in resected stage III melanoma: study protocol.

INTRODUCTION:In the new era of effective systemic therapies for advanced melanoma, early detection of lower volume recurrent disease using surveillance imaging can improve survival. However, intensive imaging follow-up strategies are likely to increase costs to health systems and may pose risks to patients. The objective of this study is to estimate from the Australian health system perspective the cost-effectiveness of four follow-up strategies in resected stage III melanoma over a 5-year period following surgical treatment with curative intent. METHODS AND ANALYSIS:A decision-analytic model will be built to estimate the costs and benefits of (1) 12 monthly, (2) 6 monthly, (3) 3-4 monthly positron emission tomography/CT imaging for 5 years, compared with (4) no imaging follow-up. The model will be populated with probabilities of disease recurrence, test performance measures using data from >1000 consecutive resected stage III melanoma patients from Melanoma Institute Australia diagnosed between 2000 and 2017. Healthcare resource use, including surveillance imaging, doctor's visits, subsequent tests and procedures to investigate suspicious findings, will be quantified from detailed patient records and valued using Australian reference pricing. Economic outcomes include cost per new distant melanoma recurrence detected and cost per diagnostic error avoided, for no imaging compared with the other strategies.Deterministic sensitivity analyses will examine the robustness of model results. ETHICS AND DISSEMINATION:This study was approved by the Sydney Local Health District, Sydney Local Health District Ethics Review Committee (RPAH Zone), AU/1/830638 and the Australian Institute of Health and Welfare (EO2019-1-454). The results of this study will be published in peer-reviewed medical and health economics journals and will inform melanoma management guidelines

Reliability of ‘in-season’ fitness assessments in youth elite soccer players: a working model for practitioners and coaches.

Purpose: To assess the reliability of a battery of field tests when performed around habitual training during one micro-cycle of the ‘in-season’ period in youth elite soccer players. Methods: n=19 English Premier League academy players (mean ± SD: age, 18.3±0.2 years; stature, 1.80±0.05 m; body mass, 76.5±7.5 kg; V̇O2 max; 62.3±4.38 ml·kg-1·min-1 Sum of 8 skinfolds; 64.8±17.4 mm) performed; ‘1RM half-back squat (HBS)’, ‘vertical jump’ (VJ), ‘Yo-Yo IR2’, ’5, 10 & 20 m, sprint’, ‘the agility T-test’ and a ‘repeated sprint ability’ assessments around their habitual ‘in-season’ training and match-play on two occasions. Typical error (TE), coefficient of variation (CV), the smallest worthwhile change (SWC) was then calculated between trials. Test usefulness was then calculated by comparing the ‘SWC’ to the TE and rated as; good, OK or marginal. The smallest difference needed to be considered real (MD), was also calculated using the equation (TE×1.96×√2). Results: Most assessments demonstrated relatively high levels of reproducibility (CV; 0.3 - 4.3 %) to witness an “almost certain beneficial change” (i.e.,>MD) changes of approximately 5% (RSAbest, RSAmean, 10m & 20m sprint, ‘agility T test’ and 1RM HBS), and 11.5% (VJ, 5m sprint, and Yo-Yo IR2) are needed. Conclusions: The present training and testing ‘model’ is reliable and could be used when evaluating the fitness of highly trained youth elite soccer players during the ‘in-season’ period

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

A survey of statistics in three UK general practice journal

Background Many medical specialities have reviewed the statistical content of their journals. To our knowledge this has not been done in general practice. Given the main role of a general practitioner as a diagnostician we thought it would be of interest to see whether the statistical methods reported reflect the diagnostic process. Methods Hand search of three UK journals of general practice namely the British Medical Journal (general practice section), British Journal of General Practice and Family Practice over a one-year period (1 January to 31 December 2000). Results A wide variety of statistical techniques were used. The most common methods included t-tests and Chi-squared tests. There were few articles reporting likelihood ratios and other useful diagnostic methods. There was evidence that the journals with the more thorough statistical review process reported a more complex and wider variety of statistical techniques. Conclusions The BMJ had a wider range and greater diversity of statistical methods than the other two journals. However, in all three journals there was a dearth of papers reflecting the diagnostic process. Across all three journals there were relatively few papers describing randomised controlled trials thus recognising the difficulty of implementing this design in general practice

A chromospheric resonance cavity in a sunspot mapped with seismology

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: The data used in this paper are from the observing campaign entitled ‘The Influence of Magnetism on Solar and Stellar Atmospheric Dynamics’ (NSO-SP proposal T1081; principal investigator: D.B.J.), which employed the ground-based Dunn Solar Telescope, USA, during July 2016. Additional supporting observations were obtained from the publicly available NASA’s Solar Dynamics Observatory (https://sdo.gsfc.nasa.gov) data archive, which can be accessed via http://jsoc.stanford.edu/ajax/lookdata.html. The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.Code availability: The numerical code (Lare2D) used in the work can be downloaded from: https://warwick.ac.uk/fac/sci/physics/research/cfsa/people/tda/larexd/Sunspots are intense collections of magnetic fields that pierce through the Sun’s photosphere, with their signatures extending upwards into the outermost extremities of the solar corona1. Cutting-edge observations and simulations are providing insights into the underlying wave generation2, configuration3,4 and damping5 mechanisms found in sunspot atmospheres. However, the in situ amplification of magnetohydrodynamic waves6, rising from a few hundreds of metres per second in the photosphere to several kilometres per second in the chromosphere7, has, until now, proved difficult to explain. Theory predicts that the enhanced umbral wave power found at chromospheric heights may come from the existence of an acoustic resonator8–10, which is created due to the substantial temperature gradients experienced at photospheric and transition region heights11. Here, we provide strong observational evidence of a resonance cavity existing above a highly magnetic sunspot. Through a combination of spectropolarimetric inversions and comparisons with high-resolution numerical simulations, we provide a new seismological approach to mapping the geometry of the inherent temperature stratifications across the diameter of the underlying sunspot, with the upper boundaries of the chromosphere ranging between 1,300 ± 200 km and 2,300 ± 250 km. Our findings will allow the three-dimensional structure of solar active regions to be conclusively determined from relatively commonplace two-dimensional Fourier power spectra. The techniques presented are also readily suitable for investigating temperature-dependent resonance effects in other areas of astrophysics, including the examination of Earth–ionosphere wave cavities12.Science and Technology Facilities Council (STFC)Invest NI and Randox Laboratories LtdSpanish Ministry of Economy and CompetitivenessEuropean Union Horizon 2020Research Council of NorwayINAF Istituto Nazionale di AstrofisicaCalifornia State University Northridg