Ability of three dairy feed evaluation systems to predict postruminal outflows of amino acids in dairy cows: A meta-analysis.

Adequate prediction of postruminal outflows of essential AA (EAA) is the starting point of balancing rations for EAA in dairy cows. The objective of this meta-analysis was to compare the performance of 3 dairy feed evaluation systems (National Research Council [NRC], Cornell Net Protein and Carbohydrate System version 6.5.5 [CNCPS], and National Academies of Sciences, Engineering and Medicine [NASEM]) to predict EAA outflows (Trp was not tested). The data set included a total of 354 treatment means from 70 duodenal and 24 omasal studies. To avoid Type I error, mean and linear biases were considered of concern if statistically significant and representing >5.0% of the observed mean. Analyses were conducted on raw observed values and on observations adjusted for the random effect of study. The analysis on raw data indicates the ability of the feed evaluation system to predict absolute values whereas the analysis on adjusted values indicates its ability to predict responses of EAA outflows to dietary changes. For the prediction of absolute values (based on raw data), NRC underpredicted outflows of all EAA, from 5.3% to 8.6% of the observed mean (%obs.mean) except for Leu, Lys, and Val; NASEM overpredicted Lys (10.8%obs.mean); and CNCPS overpredicted Arg, His, Lys, Met, and Val (5.2 to 26.0%obs.mean). No EAA had a linear bias of concern with NASEM, followed by NRC for His (6.8%obs.mean), and CNCPS for all EAA (5.6 to 12.2%obs.mean) except Leu, Phe, and Thr. In contrast, for the prediction of responses to dietary changes (based on adjusted data), NRC had 2 EAA presenting a linear bias of concern, followed by NASEM and CNCPS with 4 and 6 EAA, respectively. Predictions of His showed a linear bias of concern (5.3 to 9.6%obs.mean) with the 3 feed evaluation systems. Measured chemistry of crude protein and EAA were reported for 1 or more feed ingredients of the ration in 36% of the studies, and resulted in decreased linear biases in the 3 feed evaluation systems. The difference in mean biases of Met outflows was systematically positive when comparing omasal versus duodenal studies. Predictions of Met outflows with NRC had a higher concordance correlation coefficient in duodenal (used to develop NRC equations) versus omasal studies, whereas the opposite was observed with CNCPS, the latter showing the lowest mean bias for Met in omasal sampling studies. The 30% difference in Met mean biases between sampling sites appeared related to a similar difference found for observed Met versus nonammonia nitrogen outflows between duodenal and omasal studies, which is independent of predictions. In conclusion, NRC and NASEM yielded accurate predictions of EAA outflows, with a small superiority of NASEM to predict absolute values, and slight superiority of NRC to predict the responses to dietary changes. In comparison, CNCPS may present mean and linear biases of concern for many EAA. Moreover, it remains to determine which sampling site is more representative of the true supply of EAA to the cows.

Shifting and Splitting of Resonance Lines due to Dynamical Friction in Plasmas.

A quasilinear plasma transport theory that incorporates Fokker-Planck dynamical friction (drag) and pitch angle scattering is self-consistently derived from first principles for an isolated, marginally unstable mode resonating with an energetic minority species. It is found that drag fundamentally changes the structure of the wave-particle resonance, breaking its symmetry and leading to the shifting and splitting of resonance lines. In contrast, scattering broadens the resonance in a symmetric fashion. Comparison with fully nonlinear simulations shows that the proposed quasilinear system preserves the exact instability saturation amplitude and the corresponding particle redistribution of the fully nonlinear theory. Even in situations in which drag leads to a relatively small resonance shift, it still underpins major changes in the redistribution of resonant particles. This novel influence of drag is equally important in plasmas and gravitational systems. In fusion plasmas, the effects are especially pronounced for fast-ion-driven instabilities in tokamaks with low aspect ratio or negative triangularity, as evidenced by past observations. The same theory directly maps to the resonant dynamics of the rotating galactic bar and massive bodies in its orbit, providing new techniques for analyzing galactic dynamics.

Boltzmann's equation at 150: Traditional and modern solution techniques for charged particles in neutral gases.

Seminal gas discharge experiments of the late 19th and early 20th centuries laid the foundations of modern physics, and the influence of this "golden era" continues to resonate well into the 21st century through modern technologies, medical applications, and fundamental scientific investigations. Key to this continuing success story has been the kinetic equation formulated by Ludwig Boltzmann in 1872, which provides the theoretical foundations necessary for analyzing such highly non-equilibrium situations. However, as discussed here, the full potential of Boltzmann's equation has been realized only in the past 50 years or so, with modern computing power and analytical techniques facilitating accurate solutions for various types of charged particles (ions, electrons, positrons, and muons) in gases. Our example of thermalization of electrons in xenon gas highlights the need for such accurate methods-the traditional Lorentz approximation is shown to be hopelessly inadequate. We then discuss the emerging role of Boltzmann's equation in determining cross sections by inverting measured swarm experiment transport coefficient data using machine learning with artificial neural networks.

A modeling approach to understanding OLED performance improvements arising from spatial variations in guest:host blend ratio.

Phosphorescent organic light emitting diodes (OLEDs) suffer from efficiency roll off, where device efficiency rapidly decays at higher luminance. One strategy to minimize this loss of efficiency at higher luminance is the use of non-uniform or graded guest:host blend ratios within the emissive layer. This work applies a multi-scale modeling framework to elucidate the mechanisms by which a non-uniform blend ratio can change the performance of an OLED. Mobility and exciton data are extracted from a kinetic Monte-Carlo model, which is then coupled to a drift diffusion model for fast sampling of the parameter space. The model is applied to OLEDs with uniform, linear, and stepwise graduations in the blend ratio in the emissive layer. The distribution of the guests in the film was found to affect the mobility of the charge carriers, and it was determined that having a graduated guest profile broadened the recombination zone, leading to a reduction in second order annihilation rates. That is, there was a reduction in triplet-triplet and triplet-polaron annihilation. Reducing triplet-triplet and triplet-polaron annihilation would lead to an improvement in device efficiency.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Factors associated with emergency admission for people dying from cancer in Northern Ireland: an observational data linkage study.

BACKGROUND: Many people living with cancer are admitted as an emergency, some just prior to diagnosis and others in their last year of life. Factors associated with accessing emergency care for people dying of cancer are complex and not well understood. This can make it difficult to have the resources and staffing in place to best care for individuals in their last year of life and their families. METHODS: This study uses routinely collected administrative data from people who died of cancer in N. Ireland (NI) during 2015 and explores how personal characteristics (e.g., gender, age) and disease related factors (e.g., tumour site, cancer stage at initial diagnosis) were associated with having an emergency admission to hospital in the last year and the last 28 days of their lives, using multivariate logistic regression. RESULTS: Almost three in four people had at least one emergency admission in the last year of life, and over one in three had an emergency admission the last 28 days of life. Patterns were similar for both time outcomes with males, people with haematological, lung or brain cancers, younger persons, those diagnosed with late-stage cancer, and people diagnosed close to time of death, being significantly more likely to have an emergency admission. While there was no significant association between deprivation and emergency admission rates, those living in urban areas were more likely to have an emergency admission in their last month of life compared to rural dwellers. Late diagnosis was evident with 538 people (12.8% of all deaths from cancer) being diagnosed within one month of death and 1242 (29%) within 3 months of death. CONCLUSION: The high level of emergency admissions points to gaps in routine end-of-life care, and the need for additional training for hospital staff including frontline emergency department (ED) staff who are often the 'gatekeepers' to emergency inpatient care for people living with cancer. The levels of late diagnosis indicate a need for increased population awareness of cancer symptoms and system change to promote earlier diagnosis.

Global contributions of milk to nutrient supplies and greenhouse gas emissions.

Globally, ruminant production systems used to synthesize meat and milk differ tremendously in terms of their efficiency, productivity, and environmental impacts. Regardless of this variability, milk has been repeatedly identified as an essential source of nutrients for humans. The objective of this work was to characterize global contributions of fluid milk to human food and nutrient supplies, greenhouse gas emissions, and water withdrawal. Data were leveraged from the United Nations Food and Agriculture Organization to estimate global supplies of agricultural products. Trade of agricultural products and waste of those products, along with use of human food for livestock feed were accounted for before estimating human nutrient supplies. The contributions of milk to human-edible nutrient supplies were then enumerated in terms of their proportion of total nutrients supplied by the agricultural system and in terms of the human population's requirement for that nutrient. We identified that fluid milk provides over 10% of consumable supplies of vitamin B12, vitamin A, riboflavin, and calcium available for humans globally. In terms of human nutrient requirements, milk provides sufficient vitamin B12 to meet the needs of over 60% of the global population, riboflavin to satisfy 50% of the population, and calcium and phosphorus for over 35% of the population. Compared with other foods, milk ranked among the highest in terms of nutrient-to-calorie ratio for numerous amino acids, phosphorus, calcium, and riboflavin. Conditional dependencies were identified between greenhouse gas emissions and ruminant milk and meat, but not between water withdrawal and milk production. When evaluating the trade-offs in nutrient use versus nutrient provision for producing milk or producing all ruminant products, the production of ruminants worldwide was associated with both net increases and net decreases of several key nutrients. Continued work focusing on strategies to reduce the environmental impact of milk production will improve the utility of milk for feeding the growing global population.

The effects of dexamethasone administration on physiological, behavioral, and production parameters in dairy cows after a difficult calving.

Dairy cows are predisposed to diseases during the postpartum period. Dystocia has been associated with increased risk for disease, which is likely the result of increased tissue trauma and stress during the prolonged parturition. To attenuate the inflammatory response seen in dystocic animals and improve well-being, we assessed the effects of a glucocorticoid, dexamethasone administered within 12 h after calving. Dystocia was defined as a difficult birth resulting in a prolonged calving (≥70 min after the amniotic sac appears) and was monitored through 3 video cameras in the close-up dry-cow pen. Cows meeting the dystocia definition were randomly assigned to receive a single intramuscular injection of either dexamethasone (DEX; 0.1 mg/kg of body weight; n = 43) or saline (CON, n = 44) within 12 h following a dystocic calving. Serum haptoglobin, blood ß-hydroxybutyrate (BHB) concentrations, body temperature, and several behaviors were measured for the first 7 d postpartum. Additionally, milk production and components for the first 120 d were recorded. Using a mixed model, the fixed effects of treatment, parity, calving assistance, and time, along with 2- and 3-way interactions, were analyzed with cow as a random effect. We observed that primiparous DEX cows had greater serum haptoglobin concentrations on d 3 and d 7 postpartum compared with primiparous CON cows. There was no difference between treatment groups for blood BHB concentrations and body temperature. Behavior was altered between treatments, with DEX cows having reduced activity for the first week postpartum, as well as less restlessness and increased lying times on some of the days following calving. Treatment interacted with time for milk yield, such that DEX cows produced 2.7 kg/d less milk than CON cows for the first month following calving. The administration of dexamethasone resulted in changes in behavioral measurements, which could suggest a reduction in discomfort; however, due to the reduction in milk yield for the first month following calving, DEX administration may not be applicable for typical farm use. Additional research is needed to investigate treatments for cows experiencing dystocia without detrimental effects on milk yield.

Ability of three dairy feed evaluation systems to predict postruminal outflows of nitrogenous compounds in dairy cows: A meta-analysis.

Adequate prediction of postruminal outflow of protein fractions is the starting point for the determination of metabolizable protein supply in dairy cows. The objective of this meta-analysis was to compare the performance of 3 dairy feed evaluation systems (National Research Council [NRC], Cornell Net Protein and Carbohydrate System [CNCPS], and National Academies of Sciences, Engineering and Medicine [NASEM]) to predict outflows (g/d) of nonammonia nitrogren (NAN), microbial N (MiN), and nonammonia nonmicrobial N (NANMN). Predictions of rumen degradabilities (% of nutrient) of protein (RDP), NDF, and starch were also evaluated. The data set included 1,294 treatment means from 312 digesta flow studies. The 3 feed evaluation systems were compared using the concordance correlation coefficient (CCC), the ratio of root mean square prediction error (RMSPE) on standard deviation of observed values (RSR), and the slope between observed and predicted values. Mean and linear biases were deemed biologically relevant and are discussed if higher than a threshold of 5% of the mean of observed values. The comparisons were done on observed values adjusted or not for the study effect; the adjustment had a small effect on the mean bias but the linear bias reflected a response to a dietary change rather than absolute predictions. For the absolute predictions of NAN and MiN, CNCPS had the best-fit statistics (8% greater CCC; 6% lower RMSPE) without any bias; NRC and NASEM underpredicted NAN and MiN, and NASEM had an additional linear bias indicating that the underprediction of MiN increased at increased predictions. For NANMN, fit statistics were similar among the 3 feed evaluation systems with no mean bias; however, the linear bias with NRC and CNCPS indicated underprediction at low predictions and overprediction at elevated predictions. On average, the CCC were smaller and RSR ratios were greater for MiN versus NAN indicating increased prediction errors for MiN. For NAN responses to a dietary change, CNCPS also had the best predictions, although the mean bias with NASEM was not biologically relevant and the 3 feed evaluation systems did not present a linear bias. However, CNCPS, but not the 2 other feed evaluation systems, presented a linear bias for MiN, with responses being overpredicted at increased predictions. For NANMN, responses were overpredicted at increased predictions for the 3 feed evaluation systems, but to a lesser extent with NASEM. The site of sampling had an effect on the mean bias of MiN and NANMN in the 3 feed evaluation systems. The mean bias of MiN was higher in omasal than duodenal studies in the 3 feed evaluation systems (from 55 to 61 g/d) and this mean bias was twice as large when 15N labeling was used as a microbial marker compared with purines. Such a difference was not observed for duodenal studies. The reasons underlying these systematic differences are not clear as the type of measurements used in the current meta-analysis does not allow to delineate if one site or one microbial marker is yielding the "true" postruminal N outflows. Rumen degradabilities of protein was underpredicted with CNCPS, and RDP responses to a dietary change was underpredicted by the 3 feed evaluation systems with increased RDP predictions. Rumen degradability of NDF was underpredicted and had poor fit statistics for NASEM compared with CNCPS. Fit statistics were similar between CNCPS and NASEM for rumen degradability of starch, but with an underprediction of the response with NASEM and absolute values being overpredicted with CNCPS. Multivariate regression analyses showed that diet characteristics were correlated with prediction errors of N outflows in each feed evaluation system. Globally, compared with NAN and NANMN, residuals of MiN were correlated with several moderators in the 3 feed evaluation systems reflecting the complexity to measure and model this outflow. In addition, residuals of NANMN were correlated positively with RDP suggesting an overestimation of this parameter. In conclusion, although progress is still to be made to improve equations predicting postruminal N outflows, the current feed evaluation systems provide sufficient precision and accuracy to predict postruminal outflows of N fractions.

The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high-grade serous ovarian cancer: a national retrospective audit.

OBJECTIVE: To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing. DESIGN: National retrospective audit. SETTING: The All Wales Medical Genomics Service (AWMGS). POPULATION: Patients with high-grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS. METHODS: Analysis of NGS data from germline and/or tumour testing. MAIN OUTCOME MEASURES: Frequency of BRCA1 and BRCA2 pathogenic variants. RESULTS: The overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone. CONCLUSIONS: Parallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high-grade serous ovarian cancer. TWEETABLE ABSTRACT: Parallel germline and tumour testing maximises BRCA pathogenic variant detection in ovarian cancer.

Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial.

Rationale: Systemic sclerosis (SSc)-pulmonary arterial hypertension (PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. Objectives: We investigated the safety and efficacy of B-cell depletion for SSc-PAH. Methods: In an NIH-sponsored, multicenter, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 patients with SSc-PAH on stable-dose standard medical therapy received two infusions of 1,000 mg rituximab or placebo administered 2 weeks apart. The primary outcome measure was the change in 6-minute-walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug responsiveness. Measurements and Main Results: We randomized 57 subjects from 2010 to 2018. In the primary analysis, using data through Week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6 ± 11.1 m vs. 0.5 ± 9.7 m; P = 0.12). Although a negative study, when data through Week 48 were also considered, the estimated change in 6MWD at Week 24 was 25.5 ± 8.8 m for rituximab and 0.4 ± 7.4 m for placebo (P = 0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of RF (rheumatoid factor), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (receiver operating characteristic area under the curve, 0.88-0.95). Conclusions: B-cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab responsiveness. Clinical trial registered with www.clinicaltrails.gov (NCT01086540).

Impacts of climate change on drinking water quality in Norway.

Climate change will lead to higher temperatures, increased precipitation and runoff, as well as more intense and frequent extreme weather events in Norway. More extreme rainfall and increased runoff are historically associated with higher concentrations of indicator bacteria, colour and turbidity in raw water of Norwegian waterworks. Regional information about the risk for drinking water deterioration by the end of the century is essential for evaluating potential treatment capacity upgrades at the waterworks. We combined locally downscaled future climate scenarios with historical associations between weather/runoff and water quality from a wide spread of waterworks in Norway. With continued climate change, we estimate higher concentrations of water quality indicators of raw water by the end of the century. The water quality is estimated to deteriorate mainly due to the projected increase in rainfall, and mainly in the Western and Northern parts of Norway. While large waterworks seem to be able to adapt to future conditions, the degradation of raw water quality may cause future challenges for the treatment processes at smaller waterworks. Combining these results with further studies of treatment effects and microbial risk assessments is needed to ensure sufficient treatment capacities of the raw water in the future.

The development and validation of the 'Good Life in the Community Scale' (GLiCS): a validation study with women migrants living in high income countries.

BACKGROUND: To date, few assessment instruments have been developed to quantitatively measure the mental health status of migrant populations specifically. This paper describes the development and preliminary assessment of the 'Good Life in the Community Scale' (GLiCS). GLiCS is a wellbeing measure for migrant women in high-income settings that was coproduced with experts by experience across two phases. METHODS: The study used a mixed-methods approach and was composed of two phases. PHASE I: 88 initial items generated using qualitative data collected in a previous study were reduced to 42 through consultation with expert advisory panels, based on whether each item was considered understandable and relevant Phase II: these 42 items were piloted with a sample of migrant women (N = 109). A preliminary exploratory factor analysis was conducted using Oblique rotation. Internal consistency was measured using McDonald's ω. Convergent validity was tested by correlating the GLiCS with the Oxford Capabilities Questionnaire Mental Health (OxCAP-MH), WHO-5 wellbeing index and Objective Social Outcomes Index (SIX). Incremental validity was tested using hierarchical regression analysis to ascertain the effect on the WHO-5 wellbeing index of: age, migration status, SIX, OxCAP-MH and GLiCS. Known groups validity, the ability a measure has to discriminate between groups likely to differ on the variables of interest, was tested between the different migrant categories using a simple between subjects ANOVA. RESULTS: Exploratory factor analysis confirmed a 17-item (three-factor: (i) access to resources, (ii) belonging and contributing, (iii) independence) scale with high internal consistency (McDonald's ω = 0.91). Convergent and incremental validity were also evidenced. CONCLUSION: The GLiCS has demonstrable good internal consistency and construct validity, and it presents a promising wellbeing measure for better understanding the experience of migrant women.

Importance of ventilation and occupancy to Mycobacterium tuberculosis transmission rates in congregate settings.

BACKGROUND: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. METHODS: We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. RESULTS: We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. CONCLUSION: Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.

Practical challenges and potential approaches to predicting low-incidence diseases on farm using individual cow data: A clinical mastitis example.

Clinical mastitis (CM) incidence is considerable in terms of cows affected per year, but cases are much less common in terms of detections per cow per milking. From a modeling perspective, where predictions are made every time any cow is milked, low CM incidence per cow day makes training, evaluating, and applying CM prediction models a challenge. The objective of this study was to build models for predicting CM incidence using time-series sensor data and choose models that maximize net return based on a cost matrix. Data collected from 2 university dairy farms, the University of Florida and Virginia Polytechnic Institute and State University, were used to gather representative data, including 110,156 milkings and 333 CM cases. Variables used in the models were milk yield, protein, lactose, fat, electrical conductivity, days in milk, lactation number, and activity as the number of steps, lying time, lying bouts, and lying bout duration. Models that predicted either likelihood of CM caused by gram-negative (GN) or gram-positive (GP) bacteria on each day were derived using extreme gradient boosting with weighting favoring true-positive cases, logistic responses, and log-loss errors. Model accuracies were determined using data randomly held out from the training set on each run. All variables considered were in terms of change (slope) over previous days, including the day CM was visually detected. The GN models had a median sensitivity (Se) of 52.6% and specificity (Sp) of 99.8%, whereas the GP models had a median Se of 37.5% and Sp of 99.9% when tested on the held-out data. In our models optimized to reduce cost from predictions, the Se was much less than Sp, suggesting that CM models might benefit from greater model weighting placed on Sp. Results also highlight the importance of positive predictive value (true positive cases per predicted positive case) along with Sp and Se, as models built on sparse data tend to predict too many false-positive cases. The calculated partial net return of our GN and GP models were -$0.15 and -$0.10 per cow per lactation, respectively, whereas International Organization for Standardization (ISO) standard models with Se of 80% and Sp of 99% would return -$1.32 per cow per lactation. Models chosen that minimized the cost to the farmer differed markedly from models that met ISO guidelines, showing asymmetry in targets between Sp and Se when the disease incidence rate is low. Because of the unique challenges that low-incidence diseases like CM present, we recommend that future CM predictive models consider the economic and practical implications in addition to the traditional model evaluation metrics.

Algorithm development for individualized precision feeding of supplemental top dresses to influence feed efficiency of dairy cattle.

Individualized, precision feeding of dairy cattle may contribute to profitable and sustainable dairy production. Feeding strategies targeted at optimizing efficiency of individual cows, rather than groups of animals with similar characteristics, is a logical goal of individualized precision feeding. However, algorithms designed to make feeding recommendations for specific animals are scarce. The objective of this study was to develop and test 2 algorithms designed to improve feed efficiency of individual cows by supplementing total mixed rations (TMR) with varying types and amounts of top-dressed feedstuffs. Twenty-four Holstein dairy cows were assigned to 1 of 3 treatment groups as follows: a control group fed a common TMR ad libitum, a group fed individually according to algorithm 1, and a group fed individually according to algorithm 2. Algorithm 1 used a mixed-model approach with feed efficiency as the response variable and automated measurements of production parameters and top-dress type as dependent variables. Cow was treated as a random effect, and cow by top-dress interactions were included if significant. Algorithm 2 grouped cows based on top-dress response efficiency structure using a principal components and k-means clustering. Both algorithms were trained over a 36-d experimental period immediately before testing, and were updated weekly during the 35-d testing period. Production performance responses for dry matter intake (DMI), milk yield, milk fat percentage and yield, milk protein percentage and yield, and feed efficiency were analyzed using a mixed-effects model with fixed effects for feeding algorithm, top dress, week, and the 2- and 3-way interactions among these variables. Milk protein percentage and feed efficiency were significantly affected by the 3-way interaction of top dress, algorithm, and week, and DMI tended to be affected by this 3-way interaction. Feeding algorithm did not affect milk yield, milk fat yield, or milk protein yield. However, feeding costs were reduced, and hence milk revenue increased on the algorithm-fed cows. The efficacy of feeding algorithms differed by top dress and time, and largely relied on DMI shifts to modulate feed efficiency. The net result, for the cumulative feeding groups, was that cows in the algorithm 1 and 2 groups earned over $0.45 and $0.70 more per head per day in comparison to cows on the TMR control, respectively. This study yielded 2 candidate approaches for efficiency-focused, individualized feeding recommendations. Refinement of algorithm selection, development, and training approaches are needed to maximize production parameters through individualized feeding.

Comparison of production-related responses to hyperinsulinemia and hypoglycemia induced by clamp procedures or heat stress of lactating dairy cattle.

Hyperinsulinemia concurrent with hypoglycemia is one of a myriad of physiological changes typically experienced by lactating dairy cows exposed to heat stress, the consequences of which are not yet well defined or understood. Therefore, the objective of this experiment was to separate the production-related effects of hyperinsulinemia with hypoglycemia from those of a hyperthermic environment. Multiparous lactating Holstein cows (n = 23; 58 ± 4 d in milk, 3.1 ± 0.3 lactations) were housed in temperature-controlled rooms and all were subjected to 4 experimental periods as follows: (1) thermoneutral (TN; temperature-humidity index of 65.1 ± 0.2; d 1-5), (2) TN + hyperinsulinemic-hypoglycemic clamp (HHC; insulin infused at 0.3 µg/kg of BW per h, glucose infused to maintain 90 ± 10% of baseline blood glucose for 96 h; d 6-10), (3) heat stress (HS; temperature-humidity index of 72.5 ± 0.2; d 16-20), and (4) HS + euglycemic clamp (EC; glucose infused to reach 100 ± 10% of TN baseline blood glucose for 96 h; d 21-25). Cows were fed and milked twice daily. Feed refusals were collected once daily for calculation of daily dry matter intake, and milk samples were collected at the beginning and end of each period for component analyses. Circulating insulin concentrations were measured in daily blood samples, whereas glucose concentrations were measured more frequently and variably in association with clamp procedures. Rectal temperatures and respiration rates were greater during HS than TN, as expected, and states of hyperinsulinemia and hypoglycemia were successfully induced by the HHC and high ambient temperatures (HS and EC). Feed intake differed based upon thermal environment as it was similar during TN and HHC periods, and declined for HS and EC. Milk production was not entirely reflective of feed intake as it was greatest during TN, intermediate during HHC, and lowest during HS and EC. All milk components differed with the experimental period, primarily in response to the thermal environment. Interestingly, TN baseline glucose concentrations were highly correlated with the change in glucose from TN to HS, and were related to glycemic status during HS. Furthermore, although few in number, those cows that failed to become hypoglycemic during HS tended to have a greater reduction in milk yield. The work presented here addresses a critical knowledge gap by broadening our understanding of the physiological response to heat stress and the related changes in glycemic state. This broadened understanding is fundamental for the development of novel, innovative management strategies as the dairy industry is compelled to become increasingly efficient in spite of global warming.

Using ultrasonic attenuation in cortical bone to infer distributions on pore size.

In this work we infer the underlying distribution on pore radius in human cortical bone samples using ultrasonic attenuation data. We first discuss how to formulate polydisperse attenuation models using a probabilistic approach and the Waterman Truell model for scattering attenuation. We then compare the Independent Scattering Approximation and the higher-order Waterman Truell models' forward predictions for total attenuation in polydisperse samples. Following this, we formulate an inverse problem under the Prohorov Metric Framework coupled with variational regularization to stabilize this inverse problem. We then use experimental attenuation data taken from human cadaver samples and solve inverse problems resulting in nonparametric estimates of the probability density function on pore radius. We compare these estimates to the "true" microstructure of the bone samples determined via microCT imaging. We find that our methodology allows us to reliably estimate the underlying microstructure of the bone from attenuation data.

The Variable CTCF Site from Drosophila melanogaster Ubx Gene is Redundant and Has no Insulator Activity.

CTCF is the most thoroughly studied chromatin architectural protein and it is found in both Drosophila and mammals. CTCF preferentially binds to promoters and insulators and is thought to facilitate formation of chromatin loops. In a subset of sites, CTCF binding depends on the epigenetic status of the surrounding chromatin. One such variable CTCF site (vCTCF) was found in the intron of the Ubx gene, in close proximity to the BRE and abx enhancers. CTCF binds to the variable site in tissues where Ubx gene is active, suggesting that the vCTCF site plays a role in facilitating contacts between the Ubx promoter and its enhancers. Using CRISPR/Cas9 and attP/attB site-specific integration methods, we investigated the functional role of vCTCF and showed that it is not required for normal Drosophila development. Furthermore, a 2161-bp fragment containing vCTCF does not function as an effective insulator when substituted for the Fab-7 boundary in the Bithorax complex. Our results suggest that vCTCF function is redundant in the regulation of Ubx.

Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome.

We aimed to establish jump power cut-offs for the composite outcome of either sarcopenia (EWGSOP2) or dysmobility syndrome using Asian and Caucasian cohorts. Estimated cut-offs were sex specific (women: < 19.0 W/kg; men: < 23.8 W/kg) but not ethnicity specific. Jump power has potential to be used in definitions of poor musculoskeletal health. PURPOSE: Weight-corrected jump power measured during a countermovement jump may be a useful tool to identify individuals with poor musculoskeletal health, but no cut-off values exist. We aimed to establish jump power cut-offs for detecting individuals with either sarcopenia or dysmobility syndrome. METHODS: Age- and sex-matched community-dwelling older adults from two cohorts (University of Wisconsin-Madison [UW], Korean Urban Rural Elderly cohort [KURE], 1:2) were analyzed. Jump power cut-offs for the composite outcome of either sarcopenia defined by EWGSOP2 or dysmobility syndrome were determined. RESULTS: The UW (n = 95) and KURE (n = 190) cohorts were similar in age (mean 75 years) and sex distribution (68% women). Jump power was similar between KURE and UW women (19.7 vs. 18.6 W/kg, p = 0.096) and slightly higher in KURE than UW in men (26.9 vs. 24.8 W/kg, p = 0.050). In UW and KURE, the prevalence of sarcopenia (7.4% in both), dysmobility syndrome (31.6% and 27.9%), or composite of either sarcopenia or dysmobility syndrome (32.6% and 28.4%) were comparable. Low jump power cut-offs for the composite outcome differed by sex but not by ethnicity (< 19.0 W/kg in women; < 23.8 W/kg in men). Low jump power was associated with elevated odds of sarcopenia (adjusted odds ratio [aOR] 4.07), dysmobility syndrome (aOR 4.32), or the composite of sarcopenia or dysmobility syndrome (aOR 4.67, p < 0.01 for all) independent of age, sex, height, and ethnicity. CONCLUSION: Sex-specific jump power cut-offs were found to detect the presence of either sarcopenia or dysmobility syndrome in older adults independent of Asian or Caucasian ethnicity.