Estimates of genetic parameters of distal limb fracture and superficial digital flexor tendon injury in UK Thoroughbred racehorses

A retrospective cohort study of distal limb fracture and superficial digital flexor tendon (SDFT) injury in Thoroughbred racehorses was conducted using health records generated by the British Horseracing Authority (BHA) between 2000 and 2010. After excluding records of horses that had both flat and jump racing starts, repeated records were reduced to a single binary record per horse (<i>n</i> = 66,507, 2982 sires), and the heritability of each condition was estimated using residual maximum likelihood (REML) with animal logistic regression models. Similarly, the heritability of each condition was estimated for the flat racing and jump racing populations separately. Bivariate mixed models were used to generate estimates of genetic correlations between SDFT injury and distal limb fracture. The heritability of distal limb fracture ranged from 0.21 to 0.37. The heritability of SDFT injury ranged from 0.31 to 0.34. SDFT injury and distal limb fracture were positively genetically correlated. These findings suggest that reductions in the risk of the conditions studied could be attempted using targeted breeding strategies

Disease and pharmacologic risk factors for first and subsequent episodes of equine laminitis: a cohort study of free-text electronic medical records

Electronic medical records from first opinion equine veterinary practice may represent a unique resource for epidemiologic research. The appropriateness of this resource for risk factor analyses was explored as part of an investigation into clinical and pharmacologic risk factors for laminitis. Amalgamated medical records from seven UK practices were subjected to text mining to identify laminitis episodes, systemic or intra-synovial corticosteroid prescription, diseases known to affect laminitis risk and clinical signs or syndromes likely to lead to corticosteroid use. Cox proportional hazard models and Prentice, Williams, Peterson models for repeated events were used to estimate associations with time to first, or subsequent laminitis episodes, respectively. Over seventy percent of horses that were diagnosed with laminitis suf- fered at least one recurrence. Risk factors for first and subsequent laminitis episodes were found to vary. Corticosteroid use (prednisolone only) was only significantly associated with subsequent, and not ini- tial laminitis episodes. Electronic medical record use for such analyses is plausible and offers important advantages over more traditional data sources. It does, however, pose challenges and limitations that must be taken into account, and requires a conceptual change to disease diagnosis which should be considered carefully

Prevalence, survival analysis and multimorbidity of chronic diseases in the general veterinarian-attended horse population of the UK

he average age of the global human population is increasing, leading to increased interest in the effects of chronic disease and multimorbidity on health resources and patient welfare. It has been posited that the average age of the general veterinarian-attended horse population of the UK is also increasing, and therefore it could be assumed that chronic diseases and multimorbidity would pose an increasing risk here also. However, evidence for this trend in ageing is very limited, and the current prevalence of many chronic diseases, and of multimorbidity, is unknown. Using text mining of first-opinion electronic medical records from seven veterinary practices around the UK, Kaplan-Meier and Cox proportional hazard modelling, we were able to estimate the apparent prevalence among veterinarian-attended horses of nine chronic diseases, and to assess their relative effects on median life expectancy following diagnosis. With these methods we found evidence of increasing population age. Multimorbidity affected 1.2% of the study population, and had a significant effect upon survival times, with co-occurrence of two diseases, and three or more diseases, leading to 6.6 and 21.3 times the hazard ratio compared to no chronic disease, respectively. Laminitis was involved in 74% of cases of multimorbidity. The population of horses attended by UK veterinarians appears to be aging, and chronic diseases and their co-occurrence are common features, and as such warrant further investigation

Long-term maintenance of arytenoid cartilage abduction and stability during exercise after laryngoplasty in 33 horses

<b>Objectives</b> To (1) assess long-term maintenance of arytenoid cartilage abduction (ACA) after laryngoplasty (LP); and (2) correlate the residual grade of ACA and postoperative abductory loss with arytenoid cartilage stability (ACS) during exercise.<p></p> <b>Study Design</b> Case series.<p></p> <b>Animals</b> Horses re-examined after laryngoplasty (n = 33).<p></p> <b>Methods</b> Of 89 LP horses (2005–2010), 33 had historic ACA data available and upper airway endoscopy at rest and during over-ground exercise (mean, 33 months; range, 4–71 months) after surgery. ACA grade at 1 and 6 weeks postoperatively were correlated to long-term ACA grade. Effects of long-term ACA grade and magnitude of postoperative abductory loss on ACS during exercise were investigated.<p></p> <b>Results</b> Median ACA grade at 1 week (n = 33) was 2, reducing to grade 3 by week 6 (n = 16). Grade 3 abduction was maintained in the long-term. Correlation between ACA at 1 week and the long-term was poor (ρ = .43, P = .1), but there was good correlation between week 6 and long-term (ρ = .89, P < .001). Arytenoid cartilage instability was observed during exercise in 7/33 of horses, and not significantly associated with the ACA grade (P = .50), or the number of grades of ACA lost (P = .64).<p></p> <b>Conclusions</b> Limited abductory loss occurs after 6 weeks postoperatively. Resting ACA grade was not a useful predictor of ACS during exercise.<p></p&gt

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

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