2 research outputs found
Genetic diversity within and between British and Irish breeds: the maternal and paternal history of native ponies.
The UK and Ireland have many native pony breeds with historical and cultural importance as well as being a source of uncharacterized genetic diversity. However, there is a lack of comprehensive research investigating their genetic diversity and phylogenetic interrelationships. Many studies contain a limited number of pony breeds or small sample sizes for these breeds. This may result in erroneous grouping of pony breeds that otherwise have intricate interrelationships with each other and are not evaluated correctly when placed as a token subset of a larger dataset. This is the first study that specifically investigates the genetic diversity within and between British and Irish native pony breeds using large sample numbers from locations of their native origin. This study used a panel of microsatellite markers and sequence analysis of the mitochondrial control region to analyze the genetic diversity within and between 11 pony breeds from Britain and Ireland. A large dataset was collected (a total of 485 animals were used for mtDNA analysis and 450 for microsatellite analysis), and previously published data were used to place the British and Irish ponies in a global context. The native ponies of Britain and Ireland were found to have had a complex history, and the interrelationships between the breeds were revealed. Overall, high levels of genetic diversity were maintained in native breeds, although some reduction was evident in small or isolated populations (Shetland, Carneddau, and Section C). Unusual mitochondrial diversity distribution patterns were apparent for the Carneddau and Dartmoor, although among breeds and global haplogroups there was a high degree of haplotype sharing evident, well-represented within British and Irish ponies. Ancestral maternal diversity was maintained by most populations, particularly the Fells and Welsh ponies, which exhibited rare and ancient lineages. The maternal and paternal histories of the breeds are distinct, with male-biased crossings between native breeds, and other shared influences, likely Arabs and Thoroughbreds, are apparent. The data generated herein provide valuable information to guide and implement the conservation of increasingly rare native genetic resources
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707