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Dairy systems require that each cow calves annually to have an efficient milk production cycle. In systems where milk production is maximized, the male offspring from dairy breed sires tend to have poor beef production traits and, therefore, can be of low economic value. Few studies have been published on the factors impacting early slaughtering of calves in peer-reviewed literature. Here we present an analysis of national data on calves slaughtered from 2018 to 2022 in Ireland. Data (Jan 2018-May 2022) on all cattle

Electronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2923 commonly used laboratory tests with HPO terms. Using these annotations, our software assesses laboratory test results and converts each result into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows readily available laboratory tests in EHR to be reused for deep phenotyping and exploits the hierarchical structure of HPO to integrate distinct tests that have comparable medical interpretations for association studies.

Key Points: Question: What are the best-performing organ dysfunction–based criteria to implement the definition of sepsis and septic shock in children with suspected infection? Findings: In this international, multicenter, retrospective cohort study including more than 3.6 million pediatric encounters, a novel score, the Phoenix Sepsis Score, was derived and validated to predict mortality in children with suspected or confirmed infection. The new criteria for pediatric sepsis and septic shock based on the score performed better than existing organ dysfunction scores and the International Pediatric Sepsis Consensus Conference criteria. Meaning: The new data-driven criteria for pediatric sepsis and septic shock based on measures of organ dysfunction had improved performance compared with prior pediatric sepsis criteria. Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria. This cohort study derives and validates novel criteria for diagnosis of pediatric sepsis and septic shock across high-resource and low-resource international settings. [ABSTRACT FROM AUTHOR]

Background: There has been very little previous research in Ireland on the opinions of farmers regarding dairy beef integration. The need for increased dairy beef integration has assumed a greater importance in Ireland in recent years due to a rapid expansion in dairy production, and associated increase in numbers of male dairy calves born on Irish farms. The objective of this study was to explore beef farmers' views on a broad range of issues related to dairy beef integration, using a survey methodology. The survey was distributed to approximately 4,250 beef farmers via email and 1,203 participated in the study.Results: The sample was composed almost entirely of beef farmers, although a very small proportion also had a dairy enterprise on their farm. Eighty percent of the farmers were concerned with the increase in the number of male dairy calves in recent years. Fifty seven percent of farmers responded that they were not willing to rear dairy bred calves for beef. Limousin, Aberdeen Angus and Hereford were the breeds farmers would be most willing to rear for beef. Good health, breed, and conformation were ranked as the main factors calf rearers consider when buying calves. Expectation of poor profit margin, expectation of poor-quality calves, and price volatility/market uncertainty were the top ranked factors dissuading farmers from rearing dairy calves for beef. The main themes arising from the qualitative question related to beef price/ability to make a profit, breed, and calf quality.Conclusions: While it is concerning that the majority of respondents expressed an unwillingness to rear dairy bred calves for beef, approximately a quarter of beef farmers indicated a willingness to rear beef-sired dairy calves for beef. In the qualitative responses, farmers described how their concerns about calf quality and their ability to make a profit from dairy bred calves would make it difficult for them to rear these calves for beef. Future strategy will have to consider how these challenges can be overcome and the issues of who bears the risks and costs associated with greater integration will have to be carefully considered.

Background: There has been very little previous research in Ireland on the farmers' opinions regarding calf welfare issues. Calf welfare, particularly for male dairy calves, has assumed greater importance in Ireland in recent years due, in part, to an increase in the number of dairy cattle over the past decade. The objective of this study was to explore dairy farmers' views on a broad range of issues related to the expansion in the dairy herd.Methods: A survey was developed to capture the views of farmers regarding male dairy calves. The majority of questions were quantitative, and a final open-ended question collected qualitative data. The survey was distributed to ~2,900 dairy farmers via text message and 881 responses were received.Results: The sample was composed almost entirely of dairy farmers, although ~20% also had a beef enterprise on their farm. Fifty eight percent of the farmers were concerned with the increase in the number of male dairy calves in recent years. The EU's abolition of milk quotas, the profitability of dairy farming compared to other farm types, and guidance from farm advisors were the three highest ranked drivers behind the increase in the number of male dairy calves. The three highest ranked options for managing the number of male dairy calves were to increase exports, encourage greater use of sexed semen, and improve the beef merit of these calves. Eighty five percent of respondents stated that individual farmers had responsibility for making changes to the number of male dairy calves. The main themes arising from analysis of the responses to the open-ended question, seeking any additional comments, were breed, beef price, live exports, and sexed semen.Conclusions: Dairy farmers recognized the responsibility they have for making changes in respect of male dairy calves, and many demonstrated a willingness to make changes in this regard. The important role of other stakeholders, particularly suckler (system where reared from calf to beef) farmers, in rearing male dairy calves for beef production was also recognized. However, the issues of who bears the risks and costs associated with greater integration will have to be carefully considered.

Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results. These more physiologically relevant culture systems hold potential for extending metabolic competence of primary hepatocyte cultures as well. In this investigation, we used computational fluid dynamics (CFD) to determine the optimal design of a flow-based hepatocyte culture system for evaluating chemical metabolism in vitro. The main design goals were 1) minimization of shear stress experienced by the cells to maximize viability, 2) rapid establishment of a uniform distribution of test compound in the chamber, and 3) delivery of sufficient oxygen to cells to support aerobic respiration. Two commercially available flow devices — RealBio® (RB) and QuasiVivo® (QV) — and a custom developed fluidized bed (FB) bioreactor were simulated, and turbulence, flow characteristics, test compound distribution, oxygen distribution, and cellular oxygen consumption were analyzed. Experimental results from the bioreactors were used to validate the simulation results.Our results indicate that maintaining adequate oxygen supply is the most important factor to the long-term viability of liver bioreactor cultures. Cell density and system flow patterns were the major determinants of local oxygen concentrations. The experimental results closely corresponded to the in silico predictions. Of the three bioreactors examined in this study, we were able to optimize the experimental conditions for long-term hepatocyte cell culture using the QV bioreactor. This system facilitated the use of low system volumes coupled with higher flow rates. This design supports cellular respiration by increasing oxygen concentrations in the vicinity of the cells, and facilitates long-term kinetic studies of low clearance test compounds. These two goals were achieved while simultaneously keeping the shear stress experienced by the cells within acceptable limits.