Interação genótipo x ambiente para produção de leite na raça Pardo Suíço, utilizando-se inferência Bayesiana.

Informações de 2.981 lactações referentes às primeiras lactações de vacas da raça Pardo-Suíça, filhas de 151 reprodutores, distribuídas em 62 rebanhos, com parições entre 1980 a 2002, foram utilizadas para se verificar a existência da heterogeneidade de variância entre rebanhos e o seu impacto na classificação de reprodutores. As produções de leite foram utilizadas para se classificar os rebanhos em níveis de alta e baixa produção. Utilizou-se um modelo animal que incluiu os efeitos fixos de rebanho-ano e estação de parto, efeito linear do período de lactação, linear e quadrático da idade da vaca ao parto, como covariáveis, além dos efeitos aleatórios de animal e ambiente temporário. Estimaram-se componentes de variância, considerando-se os rebanhos como uma única amostra e assumindo-se a produção de leite em cada nível de produção como característica diferente. Médias e componentes de variância foram maiores para o nível de alta produção, caracterizando a presença de heterogeneidade de variância entre os rebanhos. As estimativas de herdabilidade foram de 0,21 em ambos os níveis para a produção de leite e de 0,25 e 0,26 para os níveis de alta e baixa produção, respectivamente. As correlações genéticas entre os níveis foram de 0,48, indicando a presença de heterogeneidade de variâncias. Correlações de Spearman entre os valores genéticos dos reprodutores preditos em análise conjunta com o nível de alta produção foram altas, enquanto que correlações baixas foram observadas para o nível de produção baixo, para os 10, 20 e 30% dos melhores reprodutores. Reprodutores com proles em rebanhos mais variáveis estariam sendo melhores classificados na avaliação genética, quando se desconsidera a heterogeneidade de variânci

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES

Pacing Ability in Elite Runners with Intellectual Impairment

Purpose. To understand how athletes invest their energy over a race, differences in pacing ability between athletes with and without intellectual impairment (II) were explored using a novel field test. Methods. Well-trained runners (n=67) participated in this study, including 34 runners with II (age = 24.4 +/- 4.5 years; IQ = 63.1 +/- 7.7) and 33 runners without II (age = 31.4 +/- 11.2 years). The ability to perform at a pre-planned submaximal pace was assessed. Two 400m running trials were performed on an athletics track, with an individually standardized velocity. In the first trial, the speed was imposed by auditory signals given in 20m-40m intervals, in combination with coach-feedback during the initial 200m. The participant was instructed to maintain this velocity without any feedback during the final 200m. In trial 2, no coach-feedback was permitted. Results. Repeated measures analyses revealed a significant between-groups effect. II-runners deviated more from the target time than runners without II. The significant trial x group interaction effect (F = 4.15, p<.05) revealed that the ability to self-regulate the pace during the final 200m improved for runners without II (Trial 1: 1.7 +/- 1.0s, Trial 2: 0.9 +/-0.8s) whereas the II-runners deviated even more in Trial 2 (4.4 +/- 4.3s), than in Trial 1 (3.2 +/- 3.9s). Conclusion. Our findings support the assumption that intellectual capacity is involved in pacing. It is demonstrated that II-runners have difficulties maintaining a preplanned submaximal velocity, and this study contributes to understanding problems II-exercisers might experience when exercising. With this field test, we can assess the impact of II on pacing and performance in individual athletes which will lead to a fair Paralympic classification-procedure

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains)

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial. Design, setting, and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976)

Intravenous Aviptadil and Remdesivir for Treatment of COVID-19-Associated Hypoxaemic Respiratory Failure in the USA (Tesico): A Randomised, Placebo-Controlled Trial

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health