9 research outputs found

    Withered Roses

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    Illustration of roses in a column; Photograph of Guy Lombardohttps://scholarsjunction.msstate.edu/cht-sheet-music/6821/thumbnail.jp

    Who do you miss? : with extra Lee Sims piano solo chorus ; Norma Leslie & Monte Vandergrift the California poppy and the sap

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    Gift of Dr. Mary Jane Esplen.Piano vocal ukulele [instrumentation]I can't help but wonder [first line]Who do you miss when you're lonesome [first line of chorus]F [key]Moderato [tempo]Popular song [form/genre]Woman flowers ; Norma Leslie & Monte Vandergrift (photograph) [illustration]Publisher's advertisement on back cover [note]Extra Lee Sims piano solo chorus on inside front cover [note

    Late referral for end-stage renal disease: a region-wide survey in the south west of England

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    Background: The proportion of patients referred for renal replacement therapy (RRT) at a late stage of disease appears to be similar to that first described nearly 20 years ago. This study investigated the current scale of the problem in a large region in England, identifying the prior health care, patient characteristics, referral pattern, and outcomes of those accepted onto RRT.Methods: Three hundred and sixty-one (88%) out of 411 patients accepted for RRT in six renal units in the South and West Region of the UK between 1 June 1996 and 31 May 1997 were studied retrospectively. We examined the history of chronic renal failure, referral path to nephrologist, management of chronic renal failure (CRF) and patient outcomes. Patients were categorized as ‘late’ if they were referred to the renal unit either within 4 months or within 1 month of requiring RRT.Results: One hundred and twenty-four (35%) patients were referred within 4 months of RRT, and 84 (23%) within 1 month. The main differences between patients referred later and other patients was seen for those referred within 1 month. These patients were older and had more co-morbidity, significantly worse laboratory parameters at the start of RRT, were less likely to have received standard treatments for CRF, had less permanent dialysis access in place at the start of RRT (18% vs 47%, P=0.001), and had a significantly longer hospital stay (18 vs 10 days, P=0.001). Seventy-four (19%) patients died in the first 6 months: 27 (32%) in the 1-month group, 46 (16%) in all others (P=0.002). We found no evidence that patients referred late had defaulted from nephrology follow-up or had an excess of rapidly progressive disease. Though data were incomplete, there was evidence of prior CRF of over 1 year in all late referral groups.Conclusion: Nearly a quarter of patients are referred for specialist nephrology treatment at a very late stage, within 1 month of RRT. They are less likely to receive interventions that could alter the progression of CRF or reduce its associated co-morbidity, have a worse clinical state at the start of RRT, longer hospitalization and poorer survival. These differences were much less marked for those referred within 1–4 months of starting RRT, although this is an insufficient time to prepare for RRT. Further research is needed to determine the missed opportunities for more proactive diagnosis and management of CRF

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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