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ABSTRACT: The performance of an adult dairy cow may be influenced by heat stress that occurs during her gestation. The present study investigated potential effects of temperature-humidity index (THI) experienced by a cow during pregnancy on the gestated daughter's performance on her first lactation, for the French Holstein and Montbéliarde dairy cattle populations. We analyzed 14 traits, all measured on genotyped cows: 305-d milk, fat, and protein yields; 305-d SCS; clinical mastitis (both occurrence and number of events); body conformation traits; and heifer and cow conception rate. To study the effect of heat stress, we considered the THI experienced by the gestating cow, averaged for each month of her pregnancy and then categorized in 7 classes (≤40, [40,45], [45,50], [50,55], [55,60], [60,65], and >65). These average THI classes were then fitted as categorical covariates in the regression models used for this study, which included other fixed effects, and the GEBV as a covariate, both specific to each trait, the latter being previously obtained from the official French evaluations. The THI effect was therefore estimated as the deviation between the observed and predicted performances. In general, the estimated heat stress effects were small, presenting limited practical impact on the studied traits, and particularly for fertility and udder health, the estimated heat stress effects were not statistically significant. For the production traits (i.e., milk, fat, and protein yields), the estimated effect associated with high THI experienced at the beginning of the gestation was negative, and slightly positive when associated with high THI experienced by the dam at the end of her pregnancy. Finally, our results suggest that under the current French climate conditions, heat stress experienced by cows during any stage of their pregnancy has limited impact on the future performance of their gestated daughters; however, we cannot exclude that a significant in utero heat stress effect may be present in climate conditions warmer than the French.

ABSTRACT: In this paper, we present a comprehensive study of gestation length (GL) in 16 cattle breeds by using large genotype and animal record databases. Data included over 20 million gestations since 2000 and genotypes from one million calves. The study addressed the GL variability within and between breeds, estimation of its direct and maternal heritability coefficients, association with fitness and several economic traits, and QTL detection. The breed average GL varied from 279.7 to 294.4 d in Holstein and Blonde d'Aquitaine breeds, respectively. Standard deviations per breed were similar and ranged from 5.2 to 5.8 d. Direct heritability (i.e., for GL defined as a trait of the calf) was moderate to high (h2 = 0.40–0.67), whereas the maternal heritability was low (0.04–0.06). Extreme breeding values for GL were strongly associated with a higher mortality during the first 2 d of life and were associated with milk production of dams for dairy breeds and precocity of females. Finally, several QTL were detected affecting GL with cumulated effects up to a few days, and at least 2 QTL were found to be shared between different breeds. Our study highlights the risks that would be associated with selection toward a reduced GL. Further genomic studies are needed to identify the causal variants and their association with juvenile mortality and other economic traits.

BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (

Abstract Background Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. Results We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. Conclusions The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

Abstract Background Nine male and eight female calves born to a Normande artificial insemination bull named “Ly” were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality. Results Using Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes. Conclusions In conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Abstract Background In the current context of climate change, livestock production faces many challenges to improve the sustainability of systems. Dairy farming, in particular, must find ways to select animals that will be able to achieve sufficient overall production while maintaining their reproductive ability in environments with increasing temperatures. With future forecasted climate conditions in mind, this study used data from Holstein and Montbeliarde dairy cattle to: (1) estimate the genetic-by-temperature-humidity index (THI) interactions for female fertility, and (2) evaluate the production-fertility trade-off with increasing values of THI. Results Two-trait random regression models were fitted for conception rate (fertility) and test-day protein yield (production). For fertility, genetic correlations between different THI values were generally above 0.75, suggesting weak genotype-by-THI interactions for conception rate in both breeds. However, the genetic correlations between the conception rate breeding values at the current average THI (THI = 50, corresponding to a 24-h average temperature of 8 °C at 50% relative humidity) and their slopes (i.e., potential reranking) for heat stress scenarios (THI > 70), were different for each breed. For Montbeliarde, this correlation tended to be positive (i.e., overall the best reproducers are less affected by heat stress), whereas for Holstein it was approximately zero. Finally, our results indicated a weak antagonism between production and fertility, although for Montbeliarde this antagonism intensified with increasing THI. Conclusions Within the range of weather conditions studied, increasing temperatures are not expected to exacerbate the fertility-production trade-off. However, our results indicated that the animals with the best breeding values for production today will be the most affected by temperature increases, both in terms of fertility and production. Nonetheless, these animals should remain among the most productive ones during heat waves. For Montbeliarde, the current selection program for fertility seems to be adequate for ensuring the adaptation of fertility traits to temperature increases, without adverse effects on production. Such a conclusion cannot be drawn for Holstein. In the future, the incorporation of a heat tolerance index into dairy cattle breeding programs would be valuable to promote the selection of animals adapted to future climate conditions.

The furrow-ridge system was designed to allow the cultivation of dryland crop species in lowlands, enabling rotation with rice. After harvesting the dryland species, farmers usually return with rice in the following cropping season, with costs associated with dismantling ridges before sowing rice. The possibility of sowing rice directly on residual ridges should be investigated to avoid these costs. The objective was to verify the ecophysiological adaptability of rice sown on residual ridges from the previous dryland crop in lowlands, and to identify possible factors impacting the physiological performance of rice plants in this new production system. The experiment was installed in the field in a randomized block design with 5 treatments and 12 replications. The treatments considered the plant’s position in the field and in the irrigation furrow. The parameters of the growth analysis were calculated using the classical method. There was no significant damage to rice plants in any part of the field, and there was no difference between plants at the top or bottom of the furrow. Therefore, there is no need to dismantle residual ridges from previous dryland crops before planting rice in the succeeding cropping season in the lowlands of Rio Grande do Sul State, Brazil.

Background: Traumatic brain injury can be caused by head impacts, but many brain injury risk estimation models are not equally accurate across the variety of impacts that patients may undergo, and the characteristics of different types of impacts are not well studied. We investigated the spectral characteristics of different head impact types with kinematics classification. Methods: Data were analyzed from 3262 head impacts from lab reconstruction, American football, mixed martial arts, and publicly available car crash data. A random forest classifier with spectral densities of linear acceleration and angular velocity was built to classify head impact types (e.g., football, car crash, mixed martial arts). To test the classifier robustness, another 271 lab-reconstructed impacts were obtained from 5 other instrumented mouthguards. Finally, with the classifier, type-specific, nearest-neighbor regression models were built for brain strain. Results: The classifier reached a median accuracy of 96% over 1000 random partitions of training and test sets. The most important features in the classification included both low- and high-frequency features, both linear acceleration features and angular velocity features. Different head impact types had different distributions of spectral densities in low- and high-frequency ranges (e.g., the spectral densities of mixed martial arts impacts were higher in the high-frequency range than in the low-frequency range). The type-specific regression showed a generally higher R2 value than baseline models without classification. Conclusion: The machine-learning-based classifier enables a better understanding of the impact kinematics spectral density in different sports, and it can be applied to evaluate the quality of impact-simulation systems and on-field data augmentation.

Background. Despite their important clinical benefits, immune checkpoint inhibitors (ICIs) are associated with a spectrum of side effects known as immune-related adverse events (irAEs). These can be of various organ system backgrounds, including dermatologic, pulmonary, gastrointestinal, and endocrine. Polyglandular endocrinopathies (PLEs) post-ICIs therapy has been reported in the literature; however, to our knowledge, only a few have been documented with pembrolizumab. Case Report. We present a case of a female patient who developed myxedema coma (MC) and adrenal insufficiency (AI) after 4 months of stopping pembrolizumab, a programed-cell death-1 inhibitor. The patient was clinically symptomatic and was subsequently treated with levothyroxine and hydrocortisone. Discussion. It is very important to be vigilant and alert in detecting MC and AI to avoid any mortality. Pembrolizumab’s effect on inducing antitumor responses leads to a wide variety of multiorgan alterations. Its role in raising the risk of all-grade endocrine disorders has been previously highlighted along with thyroidal dysfunctions. Our patient’s presentation falls within the literature-based median time for hypothyroidism and AI with respect to the period from the initiation of pembrolizumab. The patient’s predisposition to hypothyroidism and the likelihood of intertwined manifestations of AI and hypothyroidism should always be considered in the setting of critical illness. Conclusion. It is of high significance to explore the mechanism of action of ICIs and their side effects. PLEs can house some endocrinologic emergencies that are life threatening.

Although women make up a significant portion of the workforce in dermatology, they remain underrepresented in academia. This study investigates the number of male and female symposium speakers at the American Academy of Dermatology annual meetings over a three-year period and compares research productivity and academic rank between the men and women invited to speak. The results demonstrate a steady increase in the representation of female symposium speakers at the conference from 2016 to 2018, although a higher proportion of invited male speakers hold professorships and leadership positions. This upward trend in women's representation may translate to more opportunities for female engagement in academic dermatology. Although women make up over 60% of residents in dermatology, they are not proportionally represented in this conference sample. This imbalance in representation demonstrates that further interventions to increase the representation of female professors and chairs may be necessary.

In anthropology, a rite of passage is a process voluntarily initiated to allow an individual or a group move through a difficult stage of transformation. The liminal period is the intermediate stage of this process. The idea of liminality has been widely used in the social sciences and in management. However, although it initially had a strong operational dimension for carrying out a transformation, it has become a simple concept describing the situation of individuals who are disoriented and sidelined. Nonetheless, organizational management needs operational tools to facilitate the integration of individuals during transition phases. This article seeks to understand how rituals can facilitate the integration process of liminal individuals. We study a case of ritual passage within a highly ritualized nonreligious organization: a Masonic lodge. We identify several mechanisms, activated through the ritual, that help to integrate liminal individuals. We analyze them through the ventriloquial perspective of communication, borrowed from the theory called Communicative Constitution of Organization (CCO). The results show that the ritual favors (1) the integration of individuals by reducing the ambiguity of the liminal situation, (2) the affirmation of a temporality, (3) the alignment of individual and collective objectives, (4) the recognition of otherness, (5) the lesser hierarchization of individuals, (6) the reduction of hyper-subjectivity, (7) the use of declarative statements, and (8) the rise in authority. We discuss the discrepancies between these results and works on liminality in management and the possible transposition of these mechanisms to various organizations.

Background Aneurysmal subarachnoid hemorrhages (aSAHs) account for 5% of all strokes, an appalling number when it comes to the second most common cause of death worldwide. The basis of the treatment is clinical support and either endovascular or surgical intervention. The purpose of the present study is to analyze if the time from the onset of the thunderclap headache until treatment intervention is related to the degree of disability after 6 months.