Time profiles of energy balance in dairy cows in association with metabolic status, inflammatory status, and disease.

The early lactation period in dairy cows is characterized by complex interactions among energy balance (EB), disease, and alterations in metabolic and inflammatory status. The objective of this study was to cluster cows based on EB time profiles in early lactation and investigate the association between EB clusters and inflammatory status, metabolic status, oxidative stress, and disease. Holstein-Friesian dairy cows (n = 153) were selected and monitored for disease treatments during wk 1 to 6 in lactation. Weekly EB was calculated based on energy intake and energy requirements for maintenance and milk yield in wk 1 to 6 in lactation. Weekly plasma samples were analyzed for metabolic variables in wk 1 to 6, and inflammatory and oxidative stress variables in wk 1, 2, and 4 in lactation. Liver activity index (LAI) was computed from plasma albumin, cholesterol, and retino-binding protein concentration. First, cows were clustered based on time profiles of EB, resulting in 4 clusters (SP: stable positive; MN: mild negative; IN: intermediate negative; SN: severe negative). Cows in the SN cluster had higher plasma nonesterified fatty acids and ß-hydroxybutyrate concentrations, compared with cows in the SP cluster, with the MN and IN cluster being intermediate. Cows in the SN cluster had a higher milk yield, lower dry matter intake in wk 1, lower insulin concentration compared with cows in the SP cluster, and lower glucose and IGF-1 concentration compared with cows in the SP and MN clusters. Energy balance clusters were not related with plasma haptoglobin, cholesterol, albumin, paraoxonase, and liver activity index (LAI). Second, cows were grouped based on health status [IHP: cows with treatment for inflammatory health problem (endometritis, fever, clinical mastitis, vaginal discharge or retained placenta); OHP: cows with no IHP but treatment for other health problem (milk fever, cystic ovaries, claw, and leg problems, rumen and intestine problems or other diseases); NHP: cows with no treatments, in the first 6 weeks after calving]. Energy balance was not different among health status groups. The IHP cows had lower nonesterified fatty acids and greater insulin concentration in plasma compared with OHP. The IHP cows had lower plasma albumin concentration, lower LAI and higher haptoglobin concentration compared with OHP and NHP. Overall, EB time profiles were associated with the metabolic status of dairy cows in early lactation, but were only limitedly related with markers of inflammation and oxidative stress status. Inflammatory and metabolic status were related to disease events in early lactation and caused prolonged effects on liver metabolism.

Kidney function, but not nitrogen excretion differs between Brown Swiss and Holstein dairy cows.

Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for dry matter content and nitrogen concentration. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01): 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l (creatinine), and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL) and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than in HO cows (P < 0.01). Urea and creatinine concentrations in urine and saliva did not differ among breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). Despite greater urea, creatinine, and SDMA concentrations in blood as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal.

A taste of space: Remote animal observations and discrete-choice models provide new insights into foraging and density dynamics for a large subarctic herbivore.

Competition for resources and space can drive forage selection of large herbivores from the bite through the landscape scale. Animal behaviour and foraging patterns are also influenced by abiotic and biotic factors. Fine-scale mechanisms of density-dependent foraging at the bite scale are likely consistent with density-dependent behavioural patterns observed at broader scales, but few studies have directly tested this assertion. Here, we tested if space use intensity, a proxy of spatiotemporal density, affects foraging mechanisms at fine spatial scales similarly to density-dependent effects observed at broader scales in caribou. We specifically assessed how behavioural choices are affected by space use intensity and environmental processes using behavioural state and forage selection data from caribou (Rangifer tarandus granti) observed from GPS video-camera collars using a multivariate discrete-choice modelling framework. We found that the probability of eating shrubs increased with increasing caribou space use intensity and cover of Salix spp. shrubs, whereas the probability of eating lichen decreased. Insects also affected fine-scale foraging behaviour by reducing the overall probability of eating. Strong eastward winds mitigated negative effects of insects and resulted in higher probabilities of eating lichen. At last, caribou exhibited foraging functional responses wherein their probability of selecting each food type increased as the availability (% cover) of that food increased. Space use intensity signals of fine-scale foraging were consistent with density-dependent responses observed at larger scales and with recent evidence suggesting declining reproductive rates in the same caribou population. Our results highlight potential risks of overgrazing on sensitive forage species such as lichen. Remote investigation of the functional responses of foraging behaviours provides exciting future applications where spatial models can identify high-quality habitats for conservation.

Effects of transport age (14 d vs. 28 d of age) on blood total cholesterol, insulin and IGF-1 concentrations of veal calves.

The main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin and IGF-1 and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 d or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first wk after birth (mean and SD: 4.4 ± 2.1 d), a day before transport (mean and SD: 25.8 ± 7.3 d) and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1 and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized linear mixed model. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28 d-old calves had higher blood cholesterol (Δ = 0.40 mmol/l) and IGF-1 (Δ = 53.6 ng/ml) concentrations, and evidence of higher insulin (Δ = 12.2 µU/ml) compared with 14 d-old calves. In wk 2 post-transport, 28-d old calves had higher blood IGF-1 (Δ = 21.1 ng/ml), with evidence of higher insulin (Δ = 12.2 µU/ml) concentrations compared with 14-d old calves. Cholesterol concentration measured one day before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (ß = 4.8 and 7.7 kg/mmol/l, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (ß = -0.55/mmol/l), with the likelihood of a calf of being treated with antibiotics (ß = -0.36/mmol/l) and other medicines (ß = -0.45/mmol/l) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both ß = -0.01/ng/ml) at the veal farm, and with fecal score recorded in wk 2 post-transport (ß = -0.004/ng/ml). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14 d old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves.

IL-10 dependent adaptation allows macrophages to adjust inflammatory responses to TLR4 stimulation history.

During an infection, innate immune cells must adjust nature and strength of their responses to changing pathogen abundances. To determine how stimulation of the pathogen sensing TLR4 shapes subsequent macrophage responses, we systematically varied priming and restimulation concentrations of its ligand KLA. We find that different priming strengths have very distinct effects at multiple stages of the signaling response, including receptor internalization, MAPK activation, cytokine and chemokine production, and nuclear translocation and chromatin association of NFκB and IκB members. In particular, restimulation-induced TNF-α production required KLA doses equal to or greater than those used for prior exposure, indicating that macrophages can detect and adaptively respond to changing TLR4 stimuli. Interestingly, while such adaptation was dependent on the anti-inflammatory cytokine IL-10, exogenous concentrations of IL-10 corresponding to those secreted after strong priming did not exert suppressive effects on TNF-α without such prior priming, confirming the critical role of TLR4 stimulation history.

Can extending time between vital sign checks improve sleep in hematopoietic stem cell transplant patients? Testing feasibility, acceptability, and preliminary efficacy.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) experience barriers to quality sleep. Frequent vital sign checks are necessary early posttransplant given risk of complications but can disrupt sleep. This study tested feasibility and acceptability of extending time between checking vitals (EVs) from every 4 to every 6 h to improve sleep. PROCEDURE: HSCT patients ages 8-21 years (N = 50, mean age = 14.06, SD = 3.58) and their caregivers were enrolled 1-2 days prior to transplant, and 40 patients completed the 15-day study (NCT04106089). Patients wore an actigraph to estimate sleep and provided self- and caregiver-report of sleep. Sleep was observed for nights 0 to +4 posttransplant, and patients were then randomized to EVs either Days +5 to +9 or +10 to +14. Patients were assessed daily for medical eligibility to receive EVs; on days patients were eligible, nightshift nurses (N = 79) reported EV acceptability. RESULTS: Of 200 potential nights for EVs (5 nights x 40 patients), patients were eligible for EVs on 126 nights (63% of eligible nights), and patients received EVs on 116 (92%) of eligible nights. Most patients received EVs ≥3 nights (n = 26, 65%, median = 3 nights). Most patients (85%), caregivers (80%), and nurses (84%) reported that patients used the additional 2 h during EVs for sleep, with reporters indicating moderate to high acceptability. There was preliminary evidence of efficacy indicated by caregiver-reported sleep disturbance and actigraphy-estimated improvements in sleep efficiency during EVs. CONCLUSION: Extending time between vitals checks is highly acceptable to patients, caregivers, and nurses, and may offer a feasible approach to improve sleep in pediatric HSCT.

Acute phase reaction to lipopolysaccharide-induced mastitis in early lactation dairy cows fed nitrogenic, glucogenic, or lipogenic diets.

The availability of certain macronutrients is likely to influence the capacity of the immune system. Therefore, we investigated the acute phase response to intramammary (i.mam.) lipopolysaccharide (LPS) in dairy cows fed a nitrogenic diet (n = 10) high in crude protein, a glucogenic diet (n = 11) high in carbohydrates and glucogenic precursors, or a lipogenic diet (n = 11) high in lipids. Thirty-two dairy cows were fed one of the dietary concentrates directly after calving until the end of trial at 27 ± 3 days in milk (mean ± standard deviation). In wk 3 of lactation, 20 µg of LPS was i.mam. injected in one quarter, and sterile NaCl (0.9%) in the contralateral quarter. Milk samples of the LPS-challenged and control quarter were taken hourly from before (0 h) until 9 h after LPS challenge and analyzed for milk amyloid A (MAA), haptoglobin (HP), and IL-8. In addition, blood samples were taken in the morning, and composite milk samples at morning and evening milkings, from 1 d before until 3 d after LPS challenge, and again on d 9, to determine serum amyloid A (SAA) and HP in blood, and MAA and HP in milk. The mRNA abundance of various immunological and metabolic factors in blood leukocytes was quantified by quantitative reverse-transcription PCR from samples taken at -18, -1, 6, 9, and 23 h relative to LPS application. The dietary concentrates did not affect any of the parameters in blood, milk, and leukocytes. The IL-8 was increased from 2 h, HP from 2 to 3 h, and MAA from 6 h relative to the LPS administration in the milk of the challenged quarter and remained elevated until 9 h. The MAA and HP were also increased at 9 h after LPS challenge in whole-udder composite milk, whereas HP and SAA in blood were increased only after 23 h. All 4 parameters were decreased again on d 9. Similar for all groups, the mRNA abundance of HP and the heat shock protein family A increased after the LPS challenge, whereas the mRNA expression of the tumor necrosis factor α and the leukocyte integrin ß 2 subunit (CD18) were decreased at 6 h after LPS challenge. The glucose transporter (GLUT)1 mRNA abundance decreased after LPS, whereas that of the GLUT3 increased, and that of the GLUT4 was not detectable. The mRNA abundance of GAPDH was increased at 9 h after LPS and remained elevated. The acute phase protein response was detected earlier in milk compared with blood indicating mammary production. However, immunological responses to LPS were not affected by the availability of specific macronutrients provided by the different diets.

Noise-resilient edge modes on a chain of superconducting qubits.

Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with [Formula: see text] parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.

Discovery of a functionally selective ghrelin receptor (GHSR1a) ligand for modulating brain dopamine.

SignificanceThe modulation of growth hormone secretagogue receptor-1a (GHSR1a) signaling is a promising strategy for treating brain conditions of metabolism, aging, and addiction. GHSR1a activation results in pleiotropic physiological outcomes through distinct and pharmacologically separable G protein- and ß-arrestin (ßarr)-dependent signaling pathways. Thus, pathway-selective modulation can enable improved pharmacotherapeutics that can promote therapeutic efficacy while mitigating side effects. Here, we describe the discovery of a brain-penetrant small molecule, N8279 (NCATS-SM8864), that biases GHSR1a conformations toward Gαq activation and reduces aberrant dopaminergic behavior in mice. N8279 represents a promising chemical scaffold to advance the development of better treatments for GHSR1a-related brain disorders involving the pathological dysregulation of dopamine.

Effect of different dietary regimens at dry-off on performance, metabolism, and immune system in dairy cows.

Concentrate withdrawal and feed restriction are commonly used to reduce milk production and to facilitate dry-off, but may impair immune function in dairy cows. We investigated the effect of feed rations providing different amounts of nutrients in combination with feed restriction on performance, endocrine, and metabolic responses, as well as on leukocyte function before and after abrupt dry-off. Forty-three cows were studied from d 12 before until d 6 after dry-off (56 d before scheduled calving). Cows were fed experimental concentrates rich in crude protein (nitrogenic, n = 14), glucogenic precursors (glucogenic, n = 14), or lipids (lipogenic, n = 15). On d 3 before dry-off, total feed allowance was restricted to 50% in half of the animals of each dietary group, whereas feed allowance remained unchanged in the other animals. Performance parameters (milk yield, milk composition, and dry matter intake) were recorded, and daily blood and milk samples were taken and analyzed for various metabolic and endocrine parameters. Additionally, activity and mRNA abundance of several genes in leukocytes were measured at selected time points before and after feed restriction and dry-off, respectively. Feed restriction immediately resulted in a negative energy balance and decreased milk production. Concomitantly, concentrations of nonesterified fatty acids increased, whereas insulin, insulin-like growth factor-1, and glucagon decreased. After dry-off, energy balance turned positive and plasma nonesterified fatty acids decreased. Plasma glucose, insulin, and insulin-like growth factor-1 concentrations increased in all groups after dry-off. Glucose, insulin, and glucagon concentrations in plasma were higher in nonrestricted compared with restricted animals after dry-off. The experimental concentrate types marginally affected the investigated metabolic and endocrine factors, with the exception of elevated milk and plasma urea concentrations in cows fed the nitrogenic concentrate. Chemotactic and phagocytic activity of leukocytes were not affected by diets, feed restriction, or dry-off. Likewise, blood leukocyte mRNA abundance encoding for tumor necrosis factor α (TNF), heat shock protein family A (HSP70), and the glucose transporters (GLUT) 1 and 3 remained unchanged throughout the study period. Overall, the short-term negative energy balance induced by feed restriction was temporarily accompanied by metabolic adaptations, but did not alter the studied factors related to the immune system. Metabolic and endocrine adaptations supporting milk synthesis were continued during the first days after dry-off despite cessation of milking. Thus, the abrupt dry-off resulted in a short-term increase of glucose and triglyceride concentrations, with a delayed endocrine response to re-establish nutrient homeostasis in blood.

Robot-assisted techniques in vascular and endovascular surgery.

For thousands of years, robots have inspired the imagination of humans, but it was only about 35 years ago that a robot was used for the first time in medicine. Since then, robot-assisted procedures have become increasingly popular in urology, general surgical specialties, and gynecology. Robot-assisted vascular surgery was first introduced in 2002 and was thought to overcome the limitations of laparoscopy. However, it did not gain widespread popularity, and its usage is still limited to a few centers worldwide. Robot-assisted endovascular procedures, on the other hand, while still in its infancy, have become a promising alternative to existing techniques. The improvements of the robotic systems promote better surgical performance and reduce occupational hazards for vascular and endovascular surgeons. A comprehensive review of literature was performed using the search terms "robotic," "robot assisted," "vascular surgery," and "aortic" for surgical procedures or "robotic," "robot assisted," and "endovascular" for endovascular procedures. Full text articles that were published between January 1990 and March 2021 were included. This review summarizes the development of the techniques for robot-assisted vascular and endovascular surgery in recent years, its outcomes, advantages, disadvantages, and perspectives.

Realizing topologically ordered states on a quantum processor.

The discovery of topological order has revised the understanding of quantum matter and provided the theoretical foundation for many quantum error­correcting codes. Realizing topologically ordered states has proven to be challenging in both condensed matter and synthetic quantum systems. We prepared the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting quantum processor. We measured a topological entanglement entropy near the expected value of ­ln2 and simulated anyon interferometry to extract the braiding statistics of the emergent excitations. Furthermore, we investigated key aspects of the surface code, including logical state injection and the decay of the nonlocal order parameter. Our results demonstrate the potential for quantum processors to provide insights into topological quantum matter and quantum error correction.

MR Imaging Differences in the Circle of Willis between Healthy Children and Adults.

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.

Before, During, and After the First Wave of COVID-19: Mortality Analyses Reveal Relevant Trends in Germany and its States until June 2020.

OBJECTIVE: Well-established mortality ratio methodology can contribute to a fuller picture of the SARS-CoV-2/COVID-19 burden of disease by revealing trends and informing mitigation strategies. This work examines respective data from Germany by way of example. METHODS: Using monthly and weekly all-cause mortality data from January 2016 to June 2020 (published by the German Federal Statistical Institute) for all ages,<65 years and≥65 years, and specified for Germany's federal states, we explored mortality as sequela of COVID-19. We analysed standardized mortality ratios (SMRs) comparing 2020 with 2016-2019 as reference years with a focus on trend detection. RESULTS: In Germany as a whole, elevated mortality in April (most pronounced for Bavaria) declined in May. The states of Hamburg and Bremen had increased SMRs in all months under study. In Mecklenburg-Western Pomerania, decreased SMRs in January turned monotonically to increased SMRs by June. Irrespective of age group, this trend was pronounced and significant. CONCLUSIONS: Increased SMRs in Hamburg and Bremen must be interpreted with caution because of potential upward distortions due to a "catchment bias". A pronounced excess mortality in April across Germany was confirmed and a hitherto undetected trend of increasing SMRs for Mecklenburg-Western Pomerania was revealed. To meet the pandemic challenge and to benefit from research based on data collected in standardized ways, national authorities should regularly conduct SMR analyses. For independent analyses, national authorities should also expedite publishing raw mortality and population data, including detailed information on age, sex, and cause of death, in the public domain.

Metabolic and endocrine responses to short-term nutrient imbalances in the feed ration of mid-lactation dairy cows.

Short-term imbalances of dietary nutrients occur during natural fluctuations in roughage quality (e.g. on pasture) or temporal shortages of supplementary feed components. In contrast to a deficiency, macronutrients (i.e. carbohydrates, proteins, lipids) beyond the adequate supply with other nutrients may, for instance, alter milk composition, increase BW or result in a greater excretion of nitrogen. Especially dairy cows with a moderate performance, in mid- or late lactation, or in extensive farming systems may be exposed to imbalanced rations. A better understanding of metabolic and endocrine responses depending on macronutrient supply may help to precisely feed dairy cows. The present study investigated short-term metabolic and endocrine responses to different levels of concentrates formulated to particularly provide one major macronutrient source (carbohydrates, proteins or lipids). Based on parity number, lactational stage, milk yield and BW, nine mid-lactating cows (211 ± 19 days in milk) were grouped into three blocks of three animals each. Concentrates (aminogenic: rich in CP and nitrogen sources; glucogenic: high content of carbohydrates and glucogenic precursors; lipogenic: high lipid content) were fed in addition to hay in a factorial arrangement at increasing levels from 2.5 to 7.5 kg/d during 9 d. Milk yield, BW and feed intake were recorded daily. Blood and milk were sampled every 3 d at the end of each concentrate level. Milk fat, protein, lactose and urea contents were determined. In blood, concentrations of various metabolites, endocrine factors and enzyme activities (e.g. glucose, non-esterified fatty acids (NEFAs), ß-hydroxybutyrate, urea, cholesterol, triglycerides, insulin, glucagon, aspartate aminotransferase (ASAT), gamma-glutamyltransferase (GGT) and glutamate dehydrogenase activity (GLDH)) were measured. Milk yield, milk composition and BW were not affected by type and level of concentrates. Feed intake increased in cows with greater amounts of the aminogenic and lipogenic concentrate compared with the glucogenic concentrate. Milk and plasma urea concentrations were elevated in the aminogenic and to a lesser extent in the lipogenic treatment compared with the glucogenic treatment. Glucose concentrations in plasma were not affected by treatments, whereas insulin and glucagon increased, and NEFA concentrations decreased only in cows fed 7.5 kg/d aminogenic concentrate compared with the glucogenic and lipogenic treatment. Activities of ASAT, GGT and GLDH as well as the total antioxidant capacity were not affected by diets. In conclusion, immediate metabolic and endocrine responses were observed due to the short-term dietary changes. Particularly, a surplus of nitrogen supply via the aminogenic diet affected metabolic responses and stimulated insulin and glucagon secretion.

Accurately computing the electronic properties of a quantum ring.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

COVID-19: Heterogeneous Excess Mortality and "Burden of Disease" in Germany and Italy and Their States and Regions, January-June 2020.

Total mortality and "burden of disease" in Germany and Italy and their states and regions were explored during the first COVID-19 wave by using publicly available data for 16 German states and 20 Italian regions from January 2016 to June 2020. Based on expectations from 2016 to 2019, simplified Standardized Mortality Ratios (SMRs) for deaths occurring in the first half of 2020 and the effect of changed excess mortality in terms of "burden of disease" were assessed. Moreover, whether two German states and 19 Italian cities appropriately represent the countries within the European monitoring of excess mortality for public health action (EuroMOMO) network was explored. Significantly elevated SMRs were observed (Germany: week 14-18, Italy: week 11-18) with SMR peaks in week 15 in Germany (1.15, 95%-CI: 1.09-1.21) and in week 13 in Italy (1.79, 95%-CI: 1.75-1.83). Overall, SMRs were 1.00 (95%-CI: 0.97-1.04) in Germany and 1.06 (95%-CI: 1.03-1.10) in Italy. Significant SMR heterogeneity was found within both countries. Age and sex were strong modifiers. Loss of life expectancy was 0.34 days (1.66 days in men) for Germany and 5.3 days (6.3 days in men) for Italy [with upper limits of 3 and 6 weeks among elderly populations (≥65 years) after maximum potential bias adjustments]. Restricted data used within EuroMOMO neither represents mortality in the countries as a whole nor in their states and regions adequately. Mortality analyses with high spatial and temporal resolution are needed to monitor the COVID-19 pandemic's course.

Pathogen dependent effects of high amounts of oxytocin on the bloodmilk barrier integrity during mastitis in dairy cows.

INTRODUCTION: The reduction of antibiotic use in food producing animals becomes increasingly important. Therefore, suitable alternatives for mastitis treatment in dairy cows have to be considered. Oxytocin (OT) induces milk ejection and hence supports milk removal from infected mammary quarters. Beyond udder emptying, the injection of very high dosages of OT causes increased somatic cell counts (SCC) in milk and enables the transfer of immunoglobulins (Ig) from blood into milk through a reduced blood-milk barrier integrity. The aim of the present study was to investigate pathogen-specific changes of SCC, the blood derived milk components lactate dehydrogenase (LDH), serum albumin (SA), and IgG in milk of cows suffering from mastitis caused by different pathogens treated with two intravenous injections of high dosages of OT (100 IU). Milk samples from 184 dairy cows from different farms were collected on day 1 (day of clinical examination and mastitis diagnosis) and on days 2, 3, 14, and 28. Bacteriological examination (day 1) identified involved pathogens. Cows were randomly assigned to treatment (OT injections on days 1 and 2) or control group (no OT). Independently of the assigned experimental group, cows received the common therapy protocol of the veterinary practice after sample collection if the general condition was affected. Milk SCC, LDH, SA, and IgG changed specifically depending on involved pathogens. Highest values of all three parameters were measured in mastitis caused by Streptococcus uberis. Changes were less pronounced with other Streptococci spp., Staphylococci spp. or Corynebacterium bovis. Oxytocin treatment did not affect any of the studied parameters independent of the involved pathogen. Only in quarters infected with Staphylococci other than Staphylococcus aureus a decreased SCC and increased IgG concentrations in quarters, where no pathogens were detected, were observed. Thus, high dosage OT administration is obviously not suitable as a stand-alone mastitis treatment in dairy cows.

INTRODUCTION: La réduction de l'utilisation d'antibiotiques chez les animaux destinés à l'alimentation devient de plus en plus importante. Par conséquent, des alternatives appropriées au traitement des mammites chez les vaches laitières doivent être envisagées. L'ocytocine (OT) induit l'éjection du lait et favorise donc l'élimination du lait des quartiers infectés. Au-delà de la vidange de la mamelle, l'injection de doses très élevées d'OT entraîne une augmentation du nombre de cellules somatiques (CSC) dans le lait et permet le transfert d'immunoglobulines (Ig) du sang vers le lait grâce à une réduction de l'intégrité de la barrière sang-lait. Le but de la présente étude était d'étudier les changements spécifiques aux agents pathogènes du CSC, les composants du lait dérivés du sang que sont la lactate déshydrogénase (LDH) et l'albumine sérique (SA) ainsi que les IgG dans le lait de vaches souffrant de mammites causées par différents agents pathogènes traités par deux injections intraveineuses de doses élevées d'OT (100 UI). Des échantillons de lait de 184 vaches laitières de différentes exploitations ont été prélevés au jour 1 (jour de l'examen clinique et diagnostic de mammite) et aux jours 2, 3, 14 et 28. L'examen bactériologique (jour 1) a identifié les agents pathogènes impliqués. Les vaches ont été assignées au hasard au traitement (injections d'OT les jours 1 et 2) ou au groupe témoin (pas d'OT). Indépendamment du groupe auquel elles étaient attribuées, les vaches ont reçu le protocole thérapeutique usuel du cabinet vétérinaire après le prélèvement de l'échantillon si leur état général était affecté. Le CSC, la LDH, la SA et les IgG du lait ont varié spécifiquement en fonction des agents pathogènes impliqués. Les valeurs les plus élevées des trois paramètres ont été mesurées dans les mammites causées par Streptococcus uberis. Les changements étaient moins prononcés avec d'autres Streptococci spp., Staphylococci spp. ou Corynebacterium bovis. Le traitement à l'ocytocine n'a affecté aucun des paramètres étudiés indépendamment de l'agent pathogène impliqué. On a uniquement observé, dans les mammites causées par des staphylocoques autres que Staphylococcus aureus, une diminution du CSC et, dans les mammites où aucun agent pathogène n'a été détecté, une augmentation des concentrations d'IgG dans les quartiers. Ainsi, l'administration d'OT à forte dose n'est pas appropriée comme traitement unique des mammites chez les vaches laitières.