Predictive models for disease detection in group-housed preweaning dairy calves using data collected from automated milk feeders.

In the United States, dairy calves are typically housed individually due to the perception of reduced risk of spreading infectious diseases between calves and the ability to monitor health on an individual calf basis. However, automated milk feeders (AMF) can provide individual monitoring of group-housed calves while allowing them to express more natural feeding behaviors and interact with each other. Research has shown that feeding behaviors recorded by AMF can be a helpful screening tool for detecting disease in dairy calves. Altogether, there is an opportunity to use the data from AMF to create a more robust and efficient model to predict disease, reducing the need for visual observation. Therefore, the objective of this observational study was to predict disease in preweaning dairy calves using AMF feeding behavior data and machine learning (ML) algorithms. This study was conducted on a dairy farm located in the Upper Midwest United States and visited weekly from July 2018 to May 2019. During farm visits, AMF data and calves' treatment records were collected, and calves were visually health-scored for attitude, ear position, ocular discharge, nasal discharge, hide dirtiness, and cough score. The final datasets used for the analyses consisted of 740 and 741 calves, with 1,007 (healthy = 594 and sick = 413) and 1,044 (healthy = 560 and sick = 484) observations (health events) for Data 1 and Data 2, respectively. Data 1 included only the weekly calf health scores observed by research personnel, whereas Data 2 included primarily daily calf treatment records by farm staff in addition to weekly health scores. Calf visit-level feeding behaviors from AMF data included milk intake (mL/d), drinking speed (mL/min), visit duration (min), rewarded (with milk being offered) and unrewarded (without milk) visits (number per d), and the interval between visits (min). Three approaches were used to predict health status: generalized linear model, random forest, and gradient boosting machine. A total of 16 models were built using different combinations of behavior parameters, including the number of rewarded visits, number of unrewarded visits, visit duration, the interval between visits, intake, intake divided by rewarded visits, drinking speed, and drinking speed divided by rewarded visits, and also calf age at the sick day as predictor variables. Of all algorithms, random forest and gradient boosting had the best performance predicting the health status of dairy calves. The results indicated that weekly health scores were not enough to predict calf health status. However, daily treatment records and AMF data were sufficient for creating predictive algorithms (e.g., F1-scores of 0.775 and 0.784 for random forest and gradient boosting, Data 2). This study suggests that ML was effective in determining the specific visit-level feeding behaviors that can be used to predict disease in group-housed preweaning dairy calves. Implementing these ML algorithms could reduce the need for visual calf observation on farms, minimizing labor time and improving calf health.

Geographical trends for automatic milking systems research in non-pasture-based dairy farms: A scoping review.

Automatic milking system (AMS) adoption in the United States is trending upward, with issues such as lower availability and increased cost of labor being factors frequently listed as motives for AMS implementation. In addition, more interest in precision dairy farming by the new generation of farmers may also help increase AMS adoption. The objective of this scoping review was to characterize the nature of the literature investigating non-pasture-based AMS and the opportunities and challenges for future research. The eligibility criteria included studies published in or after the year 2000, with full text in English, of at least 500 words, examining various outcomes related to AMS in non-pasture-based dairy farms. Six electronic databases were searched: Biosis (Web of Science), CAB Abstracts (CAB Direct), Medline (PubMed), PubAg, AGRIS (FAO), and Scopus (Elsevier). The review focused on studies with objectives, characteristics, farms, and AMS information. A total of 4,292 titles and abstracts were screened, and 536 studies were finally included. Most of the studies were conducted in Europe (73.5%), among commercial herds (67.9%), comprising Holstein cows (57.7%), using Lely and DeLaval brands (45.4% vs. 39.7%), with free-flow traffic (52.7%). The main research topics investigated were milk production, milk composition, and AMS efficiency, followed by behavior and welfare, health disorders (especially mastitis), and nutrition in Europe and other regions. At the same time, in the United States, trends were similar, except for nutrition. Since 2016, there has been an increased interest in studies on energy and water consumption, technological development, environment (enteric emissions), reproduction, genetics, and longevity or culling. However, the small number of studies and unclear characterization of what is optimum for reproductive management, other health disorders, economics, and water and energy consumption suggest a need for future research.

Myocardial injury in patients with acute ischemic stroke detected by cardiovascular magnetic resonance imaging.

BACKGROUND: Patients with acute ischemic stroke (AIS) are at high risk of adverse cardiovascular events. Until now, the burden of myocardial injury derived from cardiovascular magnetic resonance imaging (CMR) has not been established in this population. METHODS: Patients with AIS underwent CMR at 3 Tesla within 120 h after the index stroke as part of a prospective, single-center study. Patients with persistent atrial fibrillation were excluded. Morphology and function of both cardiac chambers and atria were assessed applying SSFP cine. Myocardial tissue differentiation was based on native and contrast-enhanced imaging including late gadolinium enhancement (LGE) after 0.15 mmol/kg gadobutrol for focal fibrosis and parametric T2- and T1-mapping for diffuse findings. To detect myocardial deformation global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain was measured applying feature tracking. Cardiac troponin was measured using a high-sensitivity assay (99th percentile upper reference limit 14 ng/L). T2 mapping values were compared with 20 healthy volunteers. RESULTS: CMR with contrast media was successfully performed in 92 of 115 patients (mean age 74 years, 40% female, known myocardial infarction 6%). Focal myocardial fibrosis (LGE) was detected in 31 of 92 patients (34%) of whom 23/31 (74%) showed an ischemic pattern. Patients with LGE were more likely to have diabetes, prior myocardial infarction, prior ischemic stroke, and to have elevated troponin levels compared to those without. Presence of LGE was accompanied by diffuse fibrosis (increased T1 native values) even in remote cardiac areas as well as reduced global radial, circumferential and longitudinal strain values. In 14/31 (45%) of all patients with LGE increased T2-mapping values were detectable. CONCLUSIONS: More than one-third of patients with AIS have evidence of focal myocardial fibrosis on CMR. Nearly half of these changes may have acute or subacute onset. These findings are accompanied by diffuse myocardial changes and reduced myocardial deformation. Further studies, ideally with serial CMR measurements during follow-up, are required to establish the impact of these findings on long-term prognosis after AIS.

Feeding behaviors collected from automated milk feeders were associated with disease in group-housed dairy calves in the Upper Midwest United States.

Automated milk feeders (AMF) are an attractive option for producers interested in adopting practices that offer greater behavioral freedom for calves and can potentially improve labor management. These feeders give farmers the opportunity to have a more flexible labor schedule and more efficiently feed group-housed calves. However, housing calves in group systems can pose challenges for monitoring calf health on an individual basis, potentially leading to increased morbidity and mortality. Feeding behavior recorded by AMF software could potentially be used as an indicator of disease. Therefore, the objective of this observational study was to investigate the association between feeding behaviors and disease in preweaning group-housed dairy calves fed with AMF. The study was conducted at a dairy farm located in the Upper Midwest United States and included a final data set of 599 Holstein heifer calves. The farm was visited on a weekly basis from May 2018, to May 2019, when calves were visually health scored and AMF data were collected. Calf health scores included calf attitude, ear position, ocular discharge, nasal discharge, hide dirtiness, cough score, and rectal temperatures. Generalized additive mixed models (GAMM) were used to identify associations between feeding behavior and disease. The final quasibinomial GAMM included the fixed (main and interactions) effects of feeding behavior at calf visit-level including milk intake (mL/d), drinking speed (mL/min), visit duration (min), rewarded (with milk being offered) and unrewarded (without milk) visits (number per day), and interval between visits (min), as well as the random effects of calf age in regard to their relationship with calf health status. Total milk intake (mL/d), drinking speed (mL/min), interval between visits (min) to the AMF, calf age (d), and rewarded visits were significantly associated with dairy calf health status. These results indicate that as total milk intake and drinking speed increased, the risk of calves being sick decreased. In contrast, as the interval between visits and age increased, the risk of calves being sick also increased. This study suggests that AMF data may be a useful screening tool for detecting disease in dairy calves. In addition, GAMM were shown to be a simple and flexible approach to modeling calf health status, as they can cope with non-normal data distribution of the response variable, capture nonlinear relationships between explanatory and response variables and accommodate random effects.

Effects of oral white willow bark (Salix alba) and intravenous flunixin meglumine on prostaglandin E2 in healthy dairy calves.

White willow bark (WWB) is commonly used in combination with other medicinal herbs and analgesics to alleviate inflammatory pain in disbudded calves under organic management, but there is no evidence to confirm an effect of WWB on inflammatory biomarkers in calves. The objective of this study was to determine whether WWB affects the inflammatory biomarker prostaglandin E2 (PGE2) in healthy dairy calves. A randomized crossover trial with 2 periods and 5 treatments was used for this experiment. A 7-d washout period was used to minimize carryover effects. The treatments were (1) 57.6 mg/kg oral WWB (low dose; L-WWB), (2) 115.1 mg/kg oral WWB (medium dose; M-WWB), (3) 230.3 mg/kg oral WWB (high dose; H-WWB), (4) 2.2 mg/kg i.v. flunixin meglumine (FM), or (5) no treatment (NT). Calves (n = 25) were randomly assigned to receive 1 of the 25 treatment sequences. Blood samples were collected at 1, 2, and 4 h after administration to determine PGE2 and salicylic acid plasma concentrations. The WWB had 2,171 µg/g (± 4.3% relative standard error) salicin (0.22%). On average, calves in the FM (721 ± 274 pg/mL) treatment had lower PGE2 than calves in all other treatments. Calves in the NT (2,606 ± 271 pg/mL), L-WWB (2,509 ± 276 pg/mL), M-WWB (2,343 ± 270 pg/mL), and H-WWB (3,039 ± 270 pg/mL) treatments had similar PGE2 averaged across sampling times. Calves in the L-WWB (23.4 ± 1.9 ng/mL), M-WWB (21.5 ± 1.9 ng/mL), and H-WWB (23.3 ± 1.9 ng/mL) treatments had similar maximum salicylic acid plasma concentrations. Results from this study indicate that the WWB doses used in this experiment were ineffective at achieving dose-dependent PGE2 and salicylic acid plasma concentration responses.

Time-resolved ß-lactam cleavage by L1 metallo-ß-lactamase.

Serial x-ray crystallography can uncover binding events, and subsequent chemical conversions occurring during enzymatic reaction. Here, we reveal the structure, binding and cleavage of moxalactam antibiotic bound to L1 metallo-ß-lactamase (MBL) from Stenotrophomonas maltophilia. Using time-resolved serial synchrotron crystallography, we show the time course of ß-lactam hydrolysis and determine ten snapshots (20, 40, 60, 80, 100, 150, 300, 500, 2000 and 4000 ms) at 2.20 Å resolution. The reaction is initiated by laser pulse releasing Zn2+ ions from a UV-labile photocage. Two metal ions bind to the active site, followed by binding of moxalactam and the intact ß-lactam ring is observed for 100 ms after photolysis. Cleavage of ß-lactam is detected at 150 ms and the ligand is significantly displaced. The reaction product adjusts its conformation reaching steady state at 2000 ms corresponding to the relaxed state of the enzyme. Only small changes are observed in the positions of Zn2+ ions and the active site residues. Mechanistic details captured here can be generalized to other MBLs.

Assessment of milk yield and composition, early reproductive performance, and herd removal in multiparous dairy cattle based on the week of diagnosis of hyperketonemia in early lactation.

The purpose of this retrospective cohort study was to evaluate the effects of the timing of hyperketonemia (HYK) diagnosis during early lactation on milk yield and composition, reproductive performance, and herd removal. Plasma ß-hydroxybutyrate (BHB) was measured twice a week during the first 2 wk of lactation in 362 multiparous Holstein cows for the diagnosis of HYK. In each week, cows were diagnosed as HYK positive (HYK+) if the plasma BHB concentrations were ≥1.2 mmol/L in at least one of the tests for the week evaluated. Milk-related outcomes (first 10 monthly milk tests) included milk yield, milk fat and protein content, milk urea nitrogen (MUN), and linear score of somatic cell count. Other performance outcomes of interest included risk of pregnancy within 150 d in milk (DIM) and herd removal (i.e., culling or death) within 300 DIM. Statistical models were built separately for cows diagnosed with HYK during the first week of lactation (wk1) and for cows diagnosed during the second week of lactation (wk2). All models for wk2 were adjusted by HYK diagnosed in wk1, along with other potential confounder variables. The association between HYK in each week and milk-related outcomes was assessed using generalized estimated equation models that accounted for repeated measures. Time to pregnancy and time to herd removal were analyzed using Cox's proportional hazard regression models. Seventy-eight cows (21.5%) tested positive for HYK during wk1, 60 cows (16.6%) in wk2, and 29 cows (8.0%) in both weeks. Hyperketonemia during wk1 was associated with a milk yield reduction of 3.7 kg [95% confidence interval (CI): -6.67 to -0.76] per cow per day throughout the lactation. Meanwhile, we did not observe evidence of an association between HYK diagnosed during wk2 and milk yield. During the first 2 monthly milk tests, cows diagnosed as HYK+ in wk1 had greater fat (0.42%; 95% CI: 0.16 to 0.67) and MUN (0.75 mg/dL; 95% CI: 0.26 to 1.24) content in milk than HYK-negative (HYK-) cows. We did not detect any evidence of an association between HYK diagnosed in wk2 and these outcomes. The HYK+ cows in wk1 had a 30% [hazard ratio (HR) = 0.70; 95% CI: 0.48 to 1.01] lower risk of pregnancy within 150 DIM and 2.48 times (95% CI: 1.63 to 2.89) higher risk of herd removal within 300 DIM than HYK- cows. Conversely, no evidence of association was observed between HYK+ cows in wk2 and risk of pregnancy by 150 DIM (HR = 0.98; 95% CI: 0.64 to 1.51) or removal from the herd within 300 DIM (HR = 0.91; 95% CI: 0.52 to 1.60). Our findings indicate that HYK diagnosed during wk1 of lactation is associated with negative performance in terms of milk yield, reproduction, and herd removal. No evidence of association was found for the same outcomes when HYK was diagnosed in wk2. Our results suggest the need to consider the timing when HYK is diagnosed when investigating its association with performance outcomes.

The effect of individual versus pair housing of dairy heifer calves during the preweaning period on measures of health, performance, and behavior up to 16 weeks of age.

Pair housing of dairy heifer calves during the preweaning period helps meet the natural social needs of the calf and has been shown to improve growth and starter intake during the preweaning period as compared with individual housing. However, there is little evidence to suggest that pair-housed calves maintain their social and growth advantages past the weaning phase. The objective of this study was to investigate the effect of pair housing on measures of calf performance, health, and behavior up to 16 wk of age. Healthy Holstein and crossbred heifer calves were enrolled in the study after colostrum feeding, with the first calf randomly assigned to 1 of 2 housing treatments: pair (PR; 2 hutches with common outdoor space) or individual (INDV; 1 hutch plus outdoor space). All calves were bucket fed 4 L of milk replacer twice daily and weaned at 50 d of age. Weaned calves (6/group) remained with their treatment group until exit from the study at 16 wk. A venous blood sample was collected from each calf between 24 h and 7 d of age to test for serum total protein (g/dL). Body weights (kg) were obtained at birth, weaning, and 16 wk. Each enrolled calf was scored for health each week and calf health treatments were also collected. A hair sample was collected from the left shoulder at birth and 16 wk to assess hair cortisol (pg/mL). At enrollment, each calf was fitted with a triaxial accelerometer on the left hind leg for continuous recording of standing and lying time (min/24 h) for 16 wk. Latency to find feed, water, and lie down (min) at entrance to the weaned pen were recorded by continuous video observation. Open field testing with a novel object was performed at 5, 10, and 16 wk. Behaviors analyzed by video observation included latency to approach the object (s), vocalizations (n), and time spent immobile, walking, or running (s/10 min). Linear mixed models were used to determine the effect of treatment (INDV or PR) on calf growth, activity, and behavioral outcomes, which accounted for time, breed, the interaction of time and treatment, the random pen, and variability in testing day and repeated measurements within calf when appropriate. Twenty-four Holstein and crossbred calves (PR: n = 12, 6 pairs; INDV: n = 12) were enrolled from November 2 to December 23, 2018. The PR calves were 7.1 kg heavier at weaning and gained 0.15 kg/d more during the preweaning period as compared with INDV calves. In the 24 h after movement to the postweaning pen, PR calves lay down for longer periods of time (14.3 vs. 11.0 ± 0.4 h/d), and PR calves urinated more during novel object testing at 5 wk of age. Our study demonstrated benefits, such as better growth and increased lying time, of pair housing calves during the preweaning period.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Acute neurological care in north-east Germany with telemedicine support (ANNOTeM): protocol of a multi-center, controlled, open-label, two-arm intervention study.

BACKGROUND: Both diagnosis and treatment of neurological emergencies require neurological expertise and are time-sensitive. The lack of fast neurological expertise in regions with underserved infrastructure poses a major barrier for state-of-the-art care of patients with acute neurological diseases and leads to disparity in provision of health care. The main purpose of ANNOTeM (acute neurological care in North East Germany with telemedicine support) is to establish effective and sustainable support structures for evidence based treatments for stroke and other neurological emergencies and to improve outcome for acute neurological diseases in these rural regions. METHODS: A "hub-and-spoke" network structure was implemented connecting three academic neurological centres ("hubs") and rural hospitals ("spokes") caring for neurological emergencies. The network structure includes (1) the establishment of a 24/7 telemedicine consultation service, (2) the implementation of standardized operating procedures (SOPs) in the network hospitals, (3) a multiprofessional training scheme, and (4) a quality management program. Data from three major health insurance companies as well as data from the quality management program are being collected and evaluated. Primary outcome is the composite of first time of receiving paid outpatient nursing care, first time of receiving care in a nursing home, or death within 90 days after hospital admission. DISCUSSION: Beyond stroke only few studies have assessed the effects of telemedically supported networks on diagnosis and outcome of neurological emergencies. ANNOTeM will provide information whether this approach leads to improved outcome. In addition, a health economic analysis will be performed. STUDY REGISTRATION: German Clinical Trials Register DRKS00013067, date of registration: November 16 th, 2017, URL: http://www.drks.de/DRKS00013068.

Estrous detection with an activity and rumination monitoring system in an organic grazing and a low-input conventional dairy herd.

The objective of this study was to evaluate estrous detection using a physical activity and rumination monitoring system in a seasonal calving organic grazing (GRAZ) and a low-input conventional (ZEROGRAZ) dairy herd. The study was conducted from June 2014 to August 2017. During each breeding season, physical activity and rumination were monitored electronically using an activity and rumination monitoring system (HR-LD tags; SCR Engineers Ltd., Netanya, Israel). Signals resulting from the activity and rumination monitoring system for individual cows were used to determine consistency of the values using this system with the breeding date of cows. Breeding dates were determined using EstrotectTM patches. The study included 1,463 breeding dates from 531 cows. Within the GRAZ herd, during the summer breeding season the monitoring system was less sensitive for estrous detection (33.8 %) than during the winter breeding season (79.8 %).The activity and rumination monitoring system had a sensitivity of 56.7 %, specificity of 99.3 % and positive predictive value of 59.8 % for the GRAZ herd, and sensitivity of 70.1 %, specificity of 99.2 % and positive predictive value of 66.3 % for the ZEROGRAZ herd. For cows that were determined to be pregnant and subsequently calved as a result of the mating, the sensitivity for estrous detection was slightly greater for the GRAZ (60.7 %) and ZEROGRAZ (72.5 %) herds. The activity and rumination monitoring system evaluated in this study has potential for estrous detection in grazing herds during the winter breeding season and in small-input dairy herds during both, winter and summer breeding seasons.

Symposium review: Future of housing for dairy cattle.

The objective of this review was to describe recent changes and expected developments in housing systems for dairy cows. These new developments should create an appropriate production environment for modern high-producing dairy cows and stimulate dairy farming-related developments in management, agro-technology, and equipment. Increased labor efficiency has been an important driver of the change from tie-stall barns to cubicle barns (also known as freestall barns). In future housing systems, the natural behavior of cows, climate control, emissions of ammonia and greenhouse gases, reuse of waste, manure quality, the aesthetics of buildings in the landscape, and capital efficiency are becoming increasingly important elements. To address future requirements, new concepts beyond cubicle barns must be developed. Freewalk housing systems; that is, loose housing systems without cubicles, would meet some of these future demands. These systems operate with composting bedding material or artificial permeable floors as lying and walking areas. However, these barns are still in development. Combinations of cubicle and freewalk housing systems, together with other techniques being developed, might become a major future housing system. Other techniques and systems that are being explored according to sustainability criteria include the multi-climate shed, the CowToilet (Hanskamp AgroTech, Doetinchem, the Netherlands) to separate feces and urine, and multifunctional buildings. These buildings and techniques can be part of land-based or, less commonly, city-based farming systems, such as floating farms.

Dysphagia Affecting Quality of Life in Cerebellar Ataxia-a Large Survey.

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment.

[Left atrial appendage occlusion in patients with nonvalvular atrial fibrillation : Present evidence, ongoing studies, open questions]. / Verschluss des linken Vorhofohrs bei nichtvalvulärem Vorhofflimmern : Datenlage, aktuelle Studien, offene Fragen.

About every fifth ischemic stroke is caused by atrial fibrillation. Oral anticoagulation is highly effective in secondary stroke prevention, but a relevant portion of patients with atrial fibrillation is not (permanently) anticoagulated for a variety of reasons. Based on present evidence, no general recommendation can be given for left atrial appendage occlusion in patients with nonvalvular atrial fibrillation. However, left atrial appendage occlusion is a treatment option after severe anticoagulation-related bleeding, if the cause of bleeding is not treatable. Left atrial appendage occlusion is critical in patients with a relative contraindication for oral anticoagulation or lack of adherence to given medication. It seems to be important that further randomized studies confirm a benefit of left atrial appendage occlusion in selected patients with nonvalvular atrial fibrillation. In addition, it is vital to clarify whether discontinuation of antiplatelets is feasible after catheter-based left atrial appendage occlusion, as antiplatelets are associated with a risk of bleeding. Within this review article, we discuss present evidence, gaps of knowledge and provide an overview on ongoing clinical studies. In addition, we summarize the design of the CLOSURE-AF study. This randomized multicenter study will start recruitment soon and is funded by the German Center for Cardiovascular Research e. V.

Short communication: Effects of mesh leggings on fly pressure and fly avoidance behaviors of pastured dairy cows.

Ectoparasitic stable flies (Stomoxys calcitrans [L.]), horn flies (Haematobia irritans [L.]), and face flies (Musca autumnalis De Geer) negatively affect dry matter intake, milk production, and health of pastured dairy cows. These flies cause fly avoidance behaviors and are a major welfare concern for dairy producers. The objective of this study was to evaluate the effects of mesh Shoofly Leggins (Stone Manufacturing & Supply, Kansas City, MO) on fly avoidance behaviors and numbers of flies attacking pastured dairy cows. In a crossover design, lactating dairy cows (n = 80) were randomly assigned to groups with and without leggings (Shoofly Leggins worn on all legs). All cows were managed in one group. Cows were observed for 2-wk periods, and then treatments were reversed in the next 2-wk interval. Counts of stable flies, horn flies, and face flies on all cows were recorded twice daily (once in morning per cow: 0930 to 1230 h; and once in the afternoon per cow: 1330 to 1630 h), 3 times per wk on Tuesday, Wednesday, and Thursday of each week during the study period. The total number of flies per cow was greater on cows with leggings than cows without leggings. The number of horn flies per cow was greater on cows in with leggings (26.4 flies/side) compared with cows without leggings (24.1 flies/side). Stable fly numbers were similar for cows with and without leggings (12.8 flies/leg). A random subset of 20 focal cows per group was observed during 5-min intervals to record frequencies of 4 behaviors: leg stomps, head tosses, skin twitches, and tail swishes. Counts of head tosses (2.6 vs. 3.1), skin twitches (20.9 vs. 19.6), and tail swishes (21.3 vs. 19.3) were similar for cows without leggings versus cows with leggings, respectively. However, foot stomps were 39% lower for cows with leggings compared with cows without leggings, and leg stomps were 26% higher in the afternoon than in the morning (2.9 vs. 2.4, respectively). A positive correlation was observed between stable and horn flies and all insect avoidance behaviors. Numbers of stable flies were 1.5 times greater in the afternoon than in the morning. The results of this study indicated that flies were associated with cow fly avoidance behaviors regardless of the use of leggings, but leggings effectively reduced foot stomps by 39%, so their use may provide some relief from stable fly injury to pastured dairy cows.

Effects of winter housing system on hygiene, udder health, frostbite, and rumination of dairy cows.

The objective of this study was to evaluate the effects of 2 winter (December to April) housing systems on dairy cow hygiene scores, frostbite, teat condition, clinical mastitis, and activity and rumination across 3 winter seasons (2013, 2014, and 2015). Certified-organic cows (n = 268) were randomly assigned to 2 treatments (2 replicates per system): (1) outdoor straw pack (outdoor) or (2) 3-sided compost-bedded pack barn (indoor). Cows calved during 2 seasons (spring or fall) at the University of Minnesota West Central Research and Outreach Center, Morris, Minnesota, organic dairy. Organic wheat straw was used as bedding for the 2 outdoor straw packs, and bedding was maintained by farm management to keep cows dry and absorb manure throughout the winter. The compost-bedded pack barn (2 pens in the barn) was bedded with organic-approved sawdust, and the bedding material was stirred twice per day with a small chisel plow. Hygiene scores were recorded biweekly as cows exited the milking parlor. Incidence of clinical mastitis was recorded in a binary manner as treated (1) or not treated (0) at least once during a lactation. Frostbite incidence was collected monthly. Activity and rumination times (daily and 2-h periods) were monitored electronically using a neck collar sensor (HR-LD Tags, SCR Dairy, Netanya, Israel). Indoor cows had greater udder hygiene scores (1.75 vs. 1.46) and greater abdomen hygiene scores (1.79 vs. 1.43) compared with outdoor cows. Additionally, the indoor cows had greater upper and lower leg hygiene scores compared with outdoor cows. Incidence of clinical mastitis was greater for indoor cows compared with outdoor cows (27.1% vs. 15.1%, respectively). Frostbite incidence was not different between indoor (30.1%) and outdoor (17.5%) cows. Daily rumination was 509 min/d for indoor cows and 530 min/d for the outdoor cows. In summary, lactating cows housed outdoors on straw-bedded packs had cleaner udders and improved udder health compared with cows housed in a compost-bedded pack barn.

Generation and manipulation of Schrödinger cat states in Rydberg atom arrays.

Quantum entanglement involving coherent superpositions of macroscopically distinct states is among the most striking features of quantum theory, but its realization is challenging because such states are extremely fragile. Using a programmable quantum simulator based on neutral atom arrays with interactions mediated by Rydberg states, we demonstrate the creation of "Schrödinger cat" states of the Greenberger-Horne-Zeilinger (GHZ) type with up to 20 qubits. Our approach is based on engineering the energy spectrum and using optimal control of the many-body system. We further demonstrate entanglement manipulation by using GHZ states to distribute entanglement to distant sites in the array, establishing important ingredients for quantum information processing and quantum metrology.

Myocardial injury in transient global amnesia: a case-control study.

BACKGROUND AND PURPOSE: Elevation of cardiac troponin (cTn), a sensitive biomarker of myocardial injury, is frequently observed in severe acute neurological disorders. Case reports suggest that cardiac dysfunction may also occur in patients with transient global amnesia (TGA). Until now, no study has systematically assessed this phenomenon. METHODS: We performed a case-control study using data of consecutive patients presenting with TGA from 2010 to 2015. Multiple logistic regression analysis accounting for age, sex and cardiovascular risk factors was performed to compare the likelihood of myocardial injury [defined as elevation of cTn > 99th percentile (≥14 ng/L); highly sensitive cardiac troponin T assay] in TGA with three reference groups: migraine with aura, vestibular neuritis and transient ischaemic attack (TIA). RESULTS: Cardiac troponin elevation occurred in 28 (25%) of 113 patients with TGA. Patients with TGA with cTn elevation were significantly older, more likely to be female and had higher blood pressure on admission compared with those without. The likelihood of myocardial injury following TGA was at least more than twofold higher compared with all three reference groups [adjusted odds ratio, 5.5; 95% confidence interval (CI), 1.2-26.4, compared with migraine with aura; adjusted odds ratio, 2.2; 95% CI, 1.2-4.4, compared with vestibular neuritis; adjusted odds ratio, 2.3; 95% CI, 1.3-4.2, compared with TIA]. CONCLUSIONS: One out of four patients with TGA had evidence of myocardial injury as assessed by highly sensitive cTn assays. The likelihood of myocardial injury associated with TGA was even higher than in TIA patients with a more pronounced cardiovascular risk profile. Our findings suggest the presence of a TGA-related disturbance of brain-heart interaction that deserves further investigation.

Milk yield and milking station visits of primiparous versus multiparous cows on automatic milking system farms in the Upper Midwest United States.

The objective of this study was to investigate milk yield and frequency of visits to the milking station of primiparous versus multiparous cows at different stages of lactation on farms with automatic milking systems (AMS) in the Upper Midwest United States. Forty farms were included in the study, and daily AMS software data were collected for 18 mo. For the investigation of milk yield and milking visits, stage of lactation was categorized into 14 periods, 7 d in length for the first 28 d in milk (DIM) and 30 d in length thereafter until 328 DIM. Cow traffic flow to the AMS (free or guided) was included in the model. For the evaluation of failures and refusals, stage of lactation was categorized into 6 periods, 7 d in length each for the first 28 DIM, and 2 periods of 150 d in length each thereafter until 328 DIM. Failures are milking station visits where a cow fails to be milked due to lack of machine attachment although it is time for the cow to be milked. Refusals are milking station visits before adequate time has passed since previous milking, thus the cow leaves the milking station without being milked. Data from lactation days beyond 328 DIM were excluded from the study. Primiparous cows in free-flow systems produced less milk than multiparous cows until the 11th stage of lactation and produced more milk from the 12th stage until the end of the study period. Primiparous cows in guided-flow systems produced less milk than multiparous cows all 14 stages of lactation, but were approaching the milk yield of multiparous cows at the end of the study period. This was a biologically normal lactation curve for primiparous cows. However, estimated peak ratio (primiparous vs. multiparous cows' peak milk yield) was lower than industry standards. Both traffic flow systems had fewer milking visits for primiparous cows compared with multiparous cows in early lactation. This lower milking frequency persisted until the 11th stage of lactation in free-flow systems. In guided-flow systems, primiparous cows were milked less frequently until the 5th stage of lactation, had similar milking frequency in the 6th stage of lactation, and were milked more frequently thereafter. Failures were greater for primiparous cows during all stages of lactation. However, the greatest differences were detected in the early stages of lactation. Primiparous cows had 0.067 more failures/cow per day on average than multiparous cows during wk 1 of lactation. For the remaining lactation stages, differences in failures ranged from 0.003 to 0.039. Refusals were less frequent (0.4 to 0.6/d) for primiparous cows during the first 2 wk of lactation, similar for wk 3 of lactation, and more frequent for the remaining lactation stages (0.10 to 0.14/d). Failures and refusals were only evaluated in free-flow systems. These findings appear to indicate a potential lagging performance for primiparous cows in early lactation as compared with multiparous cows. Additional investigation into improving the adaptation of primiparous cows to AMS in early lactation may be warranted.

Effects of winter housing systems on production, economics, body weight, body condition score, and bedding cultures for organic dairy cows.

Certified-organic dairy cows (n = 268) were used to evaluate the effect of 2 winter (December to April) housing systems on milk production, somatic cell score (SCS), body weight, body condition score (BCS), and economics across 3 winter seasons (2013, 2014, and 2015). Bedding cultures from the housing systems were also evaluated. Cows were randomly assigned to 2 treatments (2 replicates per group): (1) outdoor (straw pack, n = 140) or (2) indoor (3-sided compost bedded pack barn, n = 128). Cows calved during 2 seasons (spring or fall) at the University of Minnesota West Central Research and Outreach Center, Morris, Minnesota, organic dairy. Milk, fat, and protein production and SCS were recorded from monthly milk recording. Body weight and BCS were recorded biweekly as cows exited the milking parlor. Bedding cultures from the housing systems were collected biweekly. Costs for key inputs and the price received for milk production were recorded for the study period and averaged for use in the profitability analysis. Energy-corrected milk and SCS were not different for the outdoor (15.1 kg/d, 2.64) and indoor (15.7 kg/d, 2.57) housing systems, respectively. In addition, cows in the outdoor and indoor housing systems were not different for body weight (528 vs. 534 kg) and BCS (3.22 vs. 3.23), respectively. Daily dry matter intake was 19.1 kg/d for the outdoor cows and 19.6 kg/d for indoor cows. The total bacteria count from bedding samples tended to be lower in the outdoor (13.0 log10 cfu/mL) compared with the indoor (14.9 log10 cfu/mL) system. Milk revenue and feed cost were not different for the 2 housing systems. Labor and bedding costs were lower and net return was higher for the outdoor housing system. The outdoor straw pack system had a $1.42/cow per day net return advantage over the indoor compost bedded pack barn. In summary, lactating cows housed outdoors on straw-bedded packs did not differ for production or SCS, or for body weight, BCS, or dry matter intake, but had greater profitability than cows housed in an indoor compost bedded pack barn.