Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-ß transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.

Development and implementation of a clinical information system-based protocol to improve nurse satisfaction of end-of-life care in a single intensive care unit.

BACKGROUND: Patients treated in Australian intensive care units (ICUs) have an overall mortality rate of 5.05%. This is due to the critical nature of their disease, the increasing proportion of patients with multiple comorbidities, and advanced age. This has made treating patients during the end of life an integral part of intensive care practice and requires a high quality of care. With the increased use of electronic clinical information systems, a standardised protocol encompassing end-of-life care may provide an efficient method for documentation, communication, and timely delivery of comfort care. OBJECTIVE: The aim of the study was to determine if an electronic clinical information system-based end-of-life care protocol improved nurses' satisfaction with the practice of end-of-life care for patients in the ICU. DESIGN: This is a prospective single-centre observational study. SETTING: The study was carried out at a 20-bed cardiothoracic and general ICU between 2015 and 2017. PARTICIPANTS: The study participants were ICU nurses. INTERVENTION: Electronic clinical information-based end-of-life care protocol was used in the study. OUTCOME: The primary outcome was nurse satisfaction obtained by a survey. RESULTS: The number of respondents for the before survey and after survey was 58 (29%) and 64 (32%), respectively. There was a significant difference between the before survey and the after survey with regard to feeling comfortable in transitioning from curative treatment (median = 2 [interquartile range {IQR} = 2, 3] vs 3 [IQR = 2, 3], p = 0.03), feeling involved in the decision to move from curative treatment to end-of-life care (median = 2 [IQR = 2, 2] vs 2 [IQR 2, 3], p = 0.049), and feeling religious beliefs/rituals should be respected during the end-of-life process (median = 4 [IQR = 3, 4] vs. 4 [IQR = 4, 4], p = 0.02). There were some practices that had a low satisfaction rate on both the before survey and after survey. However, a high proportion of nurses were satisfied with many of the end-of-life care practices. CONCLUSION: The nurses were highly satisfied with many aspects of end-of-life care practices in this unit. The use of an electronic clinical information system-based protocol improved nurse satisfaction and perception of quality of end-of-life care practices for three survey questions.

HIV prevalence and HIV clinical outcomes of transgender and gender-diverse people in England.

OBJECTIVES: We provide the first estimate of HIV prevalence among trans and gender-diverse people living in England and compare outcomes of people living with HIV according to gender identity. METHODS: We analysed a comprehensive national HIV cohort and a nationally representative self-reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two-step question co-designed with community members and civil society. Responses were validated by clinic follow-up and/or self-report. Population estimates were obtained from national government offices. RESULTS: In 2017, HIV prevalence among trans and gender-diverse people was estimated at 0.46-4.78 per 1000, compared with 1.7 (95% credible interval: 1.6-1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender-diverse. Compared with cisgender people, trans and gender-diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self-care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups. CONCLUSIONS: HIV prevalence among trans and gender-diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender-diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people.

Branched-chain amino acids: Abundance of their transporters and metabolizing enzymes in adipose tissue, skeletal muscle, and liver of dairy cows at high or normal body condition.

Branched-chain amino acids (BCAA) are major components of milk protein and important precursors for nonessential AA. Thus, the BCAA transport and break-down play a key role in the metabolic adaptation to the high nutrient demands in lactation. However, in monogastrics, increased BCAA levels have been linked with obesity and certain metabolic disorders such as impaired insulin sensitivity. Our objective was to study the effect of over-conditioning at calving on plasma BCAA levels as well as the tissue abundance of the most relevant BCAA transporters and degrading enzymes in dairy cows during late pregnancy and early lactation. Thirty-eight Holstein cows were allocated 15 wk antepartum to either a normal- (NBCS) or over-conditioned (HBCS) group, receiving 6.8 or 7.2 MJ of NEL/kg of DM, respectively, during late lactation to reach the targeted differences in body condition score (BCS) and back fat thickness (BFT; NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until dry-off. During the dry period and next lactation, cows were fed the same diets, whereby differences in BCS and BFT were maintained: prepartum means were 3.16 ± 0.06 and 1.03 ± 0.07 cm (NBCS) vs. 3.77 ± 0.08 and 1.89 ± 0.11 cm (HBCS), postpartum means were 2.89 ± 0.06 and 0.81 ± 0.05 cm (NBCS) vs. 3.30 ± 0.06 and 1.38 ± 0.08 cm (HBCS). Blood and biopsies from liver, semitendinosus muscle, and subcutaneous adipose tissue (scAT) were sampled at d 49 antepartum, 3, 21, and 84 postpartum. Free BCAA were analyzed and the mRNA abundance of solute carrier family 1 member 5 (SLC1A5), SLC7A5, and SLC38A2 as well as branched-chain aminotransferase 2 (BCAT2), branched-chain α-keto acid dehydrogenase E1α (BCKDHA), and branched-chain α-keto acid dehydrogenase E1ß (BCKDHB) as well as the protein abundance of BCKDHA were assessed. Concentrations of all BCAA changed with time, most markedly in HBCS cows, with a nadir around calving. Apart from Ile, neither individual nor total BCAA differed between groups. The HBCS group had greater BCKDHA mRNA as well as higher prepartum BCKDHA protein abundance in scAT than NBCS cows, pointing to a greater oxidative capacity for the irreversible degradation of BCAA transamination products in scAT of over-conditioned cows. Prepartum hepatic BCKDHA protein abundance was lower in HBCS than in NBCS cows. In both groups, SLC1A5, SLC7A5, and BCAT2 mRNA were most abundant in scAT, whereas SLC38A2 was higher in scAT and muscle compared with liver, and BCKDHA and BCKDHB mRNA were greatest in liver and muscle, respectively. Our results indicate that scAT may be a major site of BCAA uptake and initial catabolism, with the former, however, being independent of BCS and time relative to calving in dairy cows.

Invited review: Abomasal damage in veal calves.

Within all cattle production systems, veal calves are the most severely affected by abomasal damage, with current prevalence at slaughter ranging from 70 to 93% of all animals affected. Although most damage is found in the pyloric region of the abomasum, fundic lesions are also found. Despite past research into the etiology of abomasal damage and the many risk factors that have been proposed, consensus on the causal factors of abomasal damage in veal calves has not yet been reached. The aim of this review was to integrate and analyze available information on the etiology of, and possible risk factors for, abomasal damage in veal calves. We describe various proposed pathways through which risk factors may contribute to damage formation and conclude that the etiology of abomasal damage is most likely multifactorial, with diet being a main contributor. Pyloric lesions, the most common type of damage in veal calves, are likely the result of large and infrequent milk and solid feed meals, whereas fundic lesions may be caused by stress, although the evidence for this is inconclusive. Providing calves with multiple smaller milk and solid feed meals (or ad libitum provision) may decrease abomasal damage. In future research, ulcers, erosions, and scars as well as fundic and pyloric lesions should be recorded separately, because etiologies of these may differ. Further research is required to understand the exact pathway(s) by which milk replacer causes abomasal damage in veal calves; that is, whether low abomasal pH, overloading, or composition are important. Further research is also required to elucidate whether rapid intake of milk replacer and solid feed, which is influenced by restricted amounts fed, inter-calf competition, and calf breed, increases abomasal damage. Research is also needed into the effect of medication and nutrient deficiencies other than iron. The types of experimental designs that can be used for future research could be enhanced if a means to assess abomasal damage antemortem is developed. We conclude that it is unlikely that abomasal or ruminal hairballs, iron deficiency, water provision, and various infections and diseases are significant contributors to abomasal damage in veal calves.

Changes in tissue abundance and activity of enzymes related to branched-chain amino acid catabolism in dairy cows during early lactation.

Branched-chain α-keto acid dehydrogenase (BCKDH) complex catalyzes the irreversible oxidative decarboxylation of branched-chain α-keto acids. This reaction is considered as the rate-limiting step in the overall branched-chain amino acid (BCAA) catabolic pathway in mammals. For characterizing the potential enzymatic involvement of liver, skeletal muscle, adipose tissue (AT), and mammary gland (MG) in BCAA metabolism during early lactation, tissue and blood samples were examined on d 1, 42, and 105 after parturition from 25 primiparous Holstein cows. Serum BCAA profiles were analyzed and the mRNA and protein abundance as well as the activity in the different tissues were assessed for the BCAA catabolic enzymes, partly for the branched-chain aminotransferase and completely for BCKDH. Total BCAA concentration in serum was lowest on d 1 after parturition and increased thereafter to a steady level for the duration of the experiment. Pronounced differences between the tissues were observed at all molecular levels. The mRNA abundance of the mitochondrial isoform of branched-chain aminotransferase (BCATm) was greatest in AT as compared with the other tissues studied, indicating that AT might be an important contributor in the initiation of BCAA catabolism in dairy cows. From the different subunits of the BCKDH E1 component, only the mRNA for the ß polypeptide (BCKDHB), not for the α polypeptide (BCKDHA), was elevated in liver. The BCKDHA mRNA abundance was similar across all tissues except muscle, which tended to lower values. Highest BCKDHA protein abundance was observed in both liver and MG, whereas BCKDHB protein was detectable in these tissues but could not be quantified. Adipose tissue and muscle only displayed abundance of the α subunit, with muscle having the lowest BCKDHA protein of all tissues. We found similarities in protein abundance for both BCKDH E1 subunits in liver and MG; however, the corresponding overall BCKDH enzyme activity was 7-fold greater in liver compared with MG, allowing for hepatic oxidation of BCAA transamination products. Reduced BCKDH activity in MG associated with no measurable activity in AT and muscle may favor sparing of BCAA for the synthesis of the different milk components, including nonessential AA. Deviating from previously published data on BCAA net fluxes and isotopic tracer studies in ruminants, our observed results might in part be due to complex counter-regulatory mechanisms during early lactation.

Epidural extension failure in obese women is comparable to that of non-obese women.

BACKGROUND: Management of labor epidurals in obese women is difficult and extension to surgical anesthesia is not always successful. Our previous retrospective pilot study found epidural extension was more likely to fail in obese women. This study used a prospective cohort to compare the failure rate of epidural extension in obese and non-obese women and to identify risk factors for extension failure. METHODS: One hundred obese participants (Group O, body mass index ≥ 40 kg/m2 ) were prospectively identified and allocated two sequential controls (Group C, body mass index ≤ 30 kg/m2 ). All subjects utilized epidural labor analgesia and subsequently required anesthesia for cesarean section. The primary outcome measure was failure of the labor epidural to be used as the primary anesthetic technique. Risk factors for extension failure were identified using Chi-squared and logistic regression. RESULTS: The odds ratio (OR) of extension failure was 1.69 in Group O (20% vs. 13%; 95% CI: 0.88-3.21, P = 0.11). Risk factors for failure in obese women included ineffective labor analgesia requiring anesthesiologist intervention, (OR 3.94, 95% CI: 1.16-13.45, P = 0.028) and BMI > 50 kg/m2 (OR 3.42, 95% CI: 1.07-10.96, P = 0.038). CONCLUSION: The failure rate of epidural extension did not differ significantly between the groups. Further research is needed to determine the influence of body mass index > 50 kg/m2 on epidural extension for cesarean section.

Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 2: The SIRT-PPARGC1A axis and its relationship with the adiponectin system.

The transition period in dairy cows is characterized by major changes in glucose and adipose tissue metabolism. The Sirtuin-1 (SIRT1) PPARγ co-activator 1α (PPARGC1A) axis might be related to the adiponectin (ADIPOQ) system to orchestrate the regulation of these processes. We aimed to assess the mRNA abundance of the aforementioned components in one visceral and one subcutaneous fat depot, together with the ADIPOQ concentrations in serum of dairy cows from late gestation to early lactation. In addition, the effect of 2 diets differing in energy density was tested. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum. From then on until d 1 antepartum, 10 animals each were assigned to either high-concentrate (60:40 concentrate:roughage) or low-concentrate (30:70) diets. Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d nicotinic acid from d -42 until d 24. From d 1 postpartum (p.p.) to d 24 p.p., the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies as well as on d -21, -14, -7, -3, 1, 3, 7, 14, 21, 28, 35, 42, 63, 82, and 100 relative to calving. Quantification of target mRNA was done using quantitative PCR and serum ADIPOQ concentration was measured via ELISA. The feeding regimen did not affect the variables examined. Serum ADIPOQ concentrations decreased toward parturition, returned to precalving levels within 1 wk after parturition, and remained on a constant level until the end of the experiment. The mRNA abundance of SIRT1, PPARGC1A, NAMPT, and the ADIPOQ receptors 1 (ADIPOR1) and 2 (ADIPOR2) changed in SCAT and RPAT during the considered time period. Comparing SCAT and RPAT, the mRNA of SIRT1, ADIPOR1, and ADIPOR2 were more abundant in RPAT, whereas PPARGC1A and NAMPT were expressed more highly in SCAT. The protein abundance of SIRT1 tended to increase from d -42 to 21. At d 21 we detected more PPARGC1A protein in the low-concentrate group as compared with the high-concentrate group. The correlations observed point to a link between these factors and might hint to a functional role of the variables in the regulation of glucose metabolism. This study substantiates the existence of the SIRT1-PPARGC1A-axis and indicates a functional relationship between SIRT1 and ADIPOR1 in bovine adipose tissue.

The role of solid feed amount and composition and of milk replacer supply in veal calf welfare.

Diets used in veal production were linked with welfare problems: that is, behavioral and gastrointestinal health disorders. This study aimed to determine how indicators of calf welfare, that is, behavior and some characteristics of the feces reflecting gastrointestinal health status, are affected by (1) different amounts and compositions of solid feed (SF), (2) the addition of ad libitum long straw to a typical veal diet, and (3) milk replacer (MR) being fed via automated milk dispensers (AMD). Two-week-old Holstein-Friesian bull calves (n=270) were used in this study. In a 4×2 factorial design, 32 pens (5 calves per pen) were allocated to different levels of SF (SF1, SF2, SF3, or SF4) and roughage-to-concentrate ratios (20:80 or 50:50). The experimental period (13 to 29wk of age) was preceded by an adaptation period (3 to 12wk of age). Targeted total dry matter (DM) intake from SF during the experimental period was 20 kg of DM for SF1, 100 kg of DM for SF2, 180 kg of DM for SF3, and 260 kg of DM for SF4. The roughage part of the SF was 50% maize silage and 50% chopped wheat straw (on a DM basis). Ten additional pens were allocated to 2 treatments with ad libitum SF, with either (1) SF components in separate troughs (SEP) or (2) SF components mixed, with the composition being equal to the choice of SEP calves in the preceding week (MIX). Another 4 pens were fitted with racks filled with long wheat straw (STR) and fed SF2 with a roughage-to-concentrate ratio of 20:80. All the aforementioned pens received MR in buckets. Finally, 8 pens were allocated to 1 of 2 SF levels: SF1 or SF2 (with a roughage-to-concentrate ratio of 50:50) and fed MR via an AMD. Milk replacer provision was adjusted every 2wk to achieve similar rates of carcass gain across treatments (excluding SEP, MIX, and STR). Behavior was recorded at 15 and 24wk using instantaneous scan sampling. The prevalence of diarrhea and clay-like feces, which signal ruminal drinking, was monitored at 14 and 25wk. More roughage, but not concentrate, increased rumination and decreased tongue playing. The STR calves had higher rumination and lower abnormal behavior levels compared with calves without ad libitum straw. Offering MR via an AMD reduced tongue playing at 15wk. Tongue playing frequency was related to both roughage amount and AMD feeding, suggesting 2 separate motivations (i.e., rumination and sucking) underlying the development of this behavior. Only SF amount affected aspects of feces: SF1 calves had the highest diarrhea incidence. No effect of diet was found on clay-like feces.

Exploring individual responses to welfare issues in growing-finishing pig feeding behaviour.

The feeding behaviour of individual growing-finishing pigs can be continuously monitored using sensors such as electronic feeding stations (EFSs), and this could be further used to monitor pig welfare. To make accurate conclusions about individual pig welfare, however, it is important to know whether deviations in feeding behaviour in response to welfare issues are shown only on average or by each individual pig. Therefore, this study aimed (1) to quantify the individual variation in feeding behaviour changes in response to a range of welfare issues, and (2) to explain this individual variation by quantifying the responses to welfare issues for specific subgroups of pigs. We monitored four rounds of 110 growing-finishing pigs each (3-4 months per round). We collected feeding behaviour data using IVOG® EFSs and identified health issues and heat stress using climate sensors and twice-weekly health observations. For each pig, a generalised additive model was fitted, which modelled feeding behaviour through time and estimated the effect of each welfare issue that the pig had suffered from. The range of these effect estimates was compared between pigs to study the individual variation in responses. Subsequently, pigs were repeatedly grouped using physical and feeding characteristics, and, with meta-subset analysis, it was determined for each group whether a deviation in response to the welfare issue (i.e. their combined effect estimates) was present. We found that the range in effect estimates was very large, approaching normal distributions for most combinations of welfare issues and feeding variables. This indicates that most pigs did not show feeding behaviour deviations during the welfare issue, while those that did could show both increases and reductions. One exception was heat stress, for which almost all pigs showed reductions in their feed intake, feeding duration and feeding frequency. When looking at subgroups of pigs, it was seen that especially for lameness and tail damage pigs with certain physical characteristics or feeding strategies did consistently deviate on some feeding components during welfare issues (e.g. only relatively heavier pigs reduced their feeding frequency during lameness). In conclusion, while detection of individual pigs suffering from heat stress using feeding variables should be feasible, detection of (mild) health issues would be difficult due to pigs responding differently, if at all, to a given health issue. For some pigs with specific physical or behavioural characteristics, nevertheless, detection of some health issues, such as lameness or tail damage, may be possible.

A preliminary study on the feasibility of two different cow-calf contact systems in a pasture-based, seasonal calving dairy system: effects on cow production and health.

Internationally, consumer dissatisfaction with cow-calf separation at birth has led to increased interest in alternative calf-rearing methods, specifically cow-calf contact (CCC) systems. The objectives of this preliminary study were to estimate whether CCC could be incorporated into an Irish spring-calving, pasture-based system, and to investigate the effects on cow milk production and health. Three systems were compared: the conventional Irish system (CONV;18 cows), cow and calf were separated < 1 h postbirth, cows were pasture-based and milked twice-a-day; a full-time access system (FT;14 cows), cow and calf were allowed constant, unrestricted access, were pasture-based, and cows were milked twice-a-day; and a part-time access system (PT;18 cows), cow and calf had unrestricted access when indoors at night, cows grazed outdoors by day while calves remained indoors, and cows were milked once-a-day in the morning. Cows were blocked and balanced across the three systems by previous lactation machine milk yield (MMY), BW, and body condition score (BCS). Following an 8-week CCC period, all calves were weaned (FT and PT underwent a 7-d gradual weaning and separation process) and all cows were milked twice-a-day. Cow MMY was recorded daily and milk composition was recorded weekly; milk data were analysed from weeks 1 to 8 (CCC period), weeks 9 to 35 (post-CCC period), and weeks 1 to 35 (cumulative lactation). Cow BW and BCS were taken weekly for weeks 1-12, and at the end of the lactation. During the CCC period, all systems differed (P < 0.001) in MMY (mean ± SEM; 24.0, 13.6, and 10.3 ± 0.50 kg/d for CONV, FT, and PT cows, respectively). After the CCC period, CONV MMY (20.2 ± 0.48 kg/d) remained higher (P < 0.001) than the FT (16.6 kg/d) and PT cows (15.7 kg/d). The FT and PT cows yielded 24 and 31% less in cumulative lactation MMY and 26 and 35% less in cumulative lactation milk solids yield, respectively, compared to CONV (5 072 ± 97.0 kg and 450 ± 8.7 kg). During the CCC period, somatic cell score was higher (P = 0.030) in PT cows (5.15 ± 0.118) compared to FT cows (4.70 ± 0.118), while CONV (4.94 ± 0.118) were inconclusive to both. The PT cows (523 ± 4.9 and 520 ± 6.8 kg) were heavier than the CONV (474 ± 4.9 and 479 ± 6.8 kg) and FT (488 ± 4.9 and 487 ± 6.8 kg) cows at week 4 and week 8 (both P < 0.001). The PT cows had higher BCS than CONV and FT at all observed times. This preliminary research suggests that although CCC was incorporated without impacting cow health, the two CCC systems investigated negatively affected cow production.

A quality improvement initiative to reduce the time to initial maternal visit in the neonatal intensive care unit.

OBJECTIVE: We aimed to reduce the time interval between an infant's admission to the Neonatal Intensive Care Unit (NICU) and first maternal interaction. METHODS: We identified three key drivers: 1. Collaboration with Labor and Delivery, 2. Education of staff and parents, and 3. Improved documentation of maternal presence. We measured the time interval from NICU admission to the initial maternal presence. We followed length of stay as a balancing measure to assay whether use of remote televisitation impeded efficient parental teaching and delayed discharge. RESULTS: We reduced the time interval from an average of 19.7 h in February 2020 to 12.3 h in June 2021. We expanded an already existing televisitation program as a surrogate to in-person interaction during COVID-19 pandemic. Televisitation did not affect in-person parental presence or LOS. CONCLUSION: Our multidisciplinary efforts resulted in a significantly accelerated time to initial maternal presence and did not prolong LOS.

Effects of roughage source, amount, and particle size on behavior and gastrointestinal health of veal calves.

The European Union 1997 Directive, stipulating that veal calves should be fed a minimum of 50 to 250 g of fibrous feed from 8 to 20 wk of age, is vague. A fibrous feed ration maximum of 250 g has been implicated in welfare issues, namely the occurrence of abnormal oral behaviors and poor gastrointestinal health. Past research suggests that this amount is insufficient to prevent the development of abnormal oral behaviors and enabling good rumen development. Different sources and particle sizes of roughage could lead to very different welfare outcomes. In a 3×2 × 2 factorial design, 240 group-housed calves (10±1 d; 46.1±0.1 kg) were fed different roughage sources (straw, maize silage, or maize cob silage; the latter 2 were dried and provided no extra moisture compared with straw) in 2 amounts (250 or 500 g of dry matter per day), and 2 particle sizes (chopped or ground). Roughage was supplemented to milk replacer (MR) from 2 wk after arrival. In addition, 60 calves were fed 1 of 3 additional control treatments: MR only (n=20), MR plus an iron supplement (n=20), or MR plus ad libitum hay (n=20). Oral behaviors were recorded using instantaneous scan sampling at 2-min intervals for 2 h in 3 periods per day, at 12 and 22 wk of age. Calves were slaughtered at 24 wk of age and rumen and abomasal health parameters were recorded. Limited provision of straw resulted in behavior comparable with that from unlimited provision of hay, with reduced tongue playing and oral manipulation of the environment, as well as increased chewing compared with diets with no roughage supplement. Straw prevented ruminal hairballs, but impaired rumen development and increased abomasal damage. A higher ration of roughage increased chewing (12 wk), decreased oral manipulation of the trough (12 and 22 wk) and the pen (22 wk), and increased rumen weight. However, more roughage led to increased abomasal damage for certain parameters. Longer feed particles had no obvious benefits for behavior, but decreased hairball prevalence. Overall, unlimited hay had the highest benefit for both behavior and gastrointestinal health. Adding iron to the MR did not alter behavior or gastrointestinal health compared with MR without iron supplement. This study demonstrated that different roughage sources, amounts, and particle sizes have different effects on veal calf behavior and gastrointestinal health, and hence on veal calf welfare.

Review: Towards an integrated concept of animal welfare.

Animal welfare is an important field of study due to animal sentience, yet there is to date no consensus on the definition of animal welfare. There have been four key developments in the field of animal welfare science since its birth: the theoretical and empirical study of affective states, and hence our understanding thereof, has increased; there has been a shift from a primary focus on unpleasant experiences towards an inclusion of pleasant experiences; there has been an increasing mention and investigation of the notion of cumulation of experiences in time, and with this, the importance of the time component of both affective states and animal welfare has come forward. Following others, we define welfare as a balance or cumulation of pleasant and unpleasant experiences over time. The time period of welfare depends on when welfare considerations are necessary, and may range from the duration of single and relatively short-term experiences to the entire life of an animal. We further propose that animal welfare conceptualised in this way can be assessed at three levels: level 1 represents the assessment of the environment and 'internal factors' such as health and personality, which interact in their impact on the affective experiences of animals; level 2 represents the assessment of affective states; and level 3 represents the assessment of the balance or cumulation of these affective states in time. The advancement of research necessitates studies to be more or less comparable, and this would be facilitated by researchers mentioning which concept of animal welfare they are basing their work on, at which level of assessment they are working, which assumptions they might be drawing from to infer welfare and which time period of interest they are focusing on, even if this is not mirrored by the timing of the assessment in practice. Assessment at levels 2 and 3 still needs much study, at both the theoretical and empirical levels, including agreements on validation tools.

Measuring corporate Paris Compliance using a strict science-based approach.

The achievement of the Paris Agreement climate goals of well-below 2 degrees of warming requires companies to align their greenhouse gas emission reductions with this goal. To measure whether companies are compliant with the Paris targets we propose several strict conditions that any emissions allocation methodology must meet before it can be classified as Paris-Compliant. Our conditions focus on the need for a common, and early as practicable, base year for all companies and consistency with an underlying Paris-aligned decarbonisation pathway. Additionally, we propose four operationalisation requirements to ensure companies can declare they are on a Paris Compliant Pathway including calculations of their carbon budgets and re-alignment pathways. Applying example Paris-Compliant Pathways and associated metrics to ten high emission electric utility companies and ten cement companies, we find that all but one of these companies are not currently Paris-compliant, with every year of delayed action increasing their required rate of decarbonisation and hence the exposure of billions of investment dollars to transition risk. Applying this proposed method will ensure the Paris carbon budget is met and that progress can be tracked accurately - an imperative for any companies and stakeholders seeking to align their decision-making with the Paris Agreement.

Impact of early dam contact on veal calf welfare.

Dairy calves, including surplus calves, are typically separated from their dam within hours of birth. The aim of this study was to assess the welfare impacts of raising surplus calves destined for veal with their dam for 2 or 4 weeks until transport. Surplus calves from one dairy farm were separated from their dam at birth (n = 39) or kept with the dam (n = 37) until transport to the veal farm at either 2 (n = 50) or 4 (n = 26) weeks of age, with abrupt separation for dam-reared calves. Calf measures of body weight, health, immunity, haematology and behaviour were recorded at the dairy and veal farms. Dam-reared calves had higher body weights in weeks 3, 4 and 5 at the DF, as well as at arrival at the veal farm, but by slaughter this advantage was lost. More dam-reared calves had fever in week 3 and showed signs of disease in week 5 at the dairy farm. Dam-reared calves did not differ in IgG, IgA or IgM levels but had higher counts of white blood cells, which could reflect a higher pathogen exposure rather than improved immunity. Dam-reared calves displayed more fear towards humans in a human approach test at 5 and 7 weeks after arrival at the veal farm, and more frequent social behaviours at the veal farm at 9 and 16 weeks of age. In conclusion, it seems that there may be both advantages and disadvantages to keeping veal calves with the dam in terms of welfare in the current system.

Hip resurfacing as an outpatient procedure: a comparison of overall cost and review of safety.

Recent advancements in arthroplasty surgical techniques and perioperative protocols have reduced the duration of hospitalization and length of recovery, allowing surgeons to perform joint replacement as an outpatient procedure. This study aims to evaluate the cost-effectiveness and safety of outpatient hip resurfacing. Two experienced surgeons performed 485 resurfacing surgeries. We retrospectively compared clinical outcomes and patient satisfaction with published outpatient total hip results. Furthermore, we compared average insurance reimbursement with that of local inpatient hip replacement. No major complications occurred within 6 weeks. Of the 39 patients with previous inpatient experience, 37 (95%) believed their outpatient experience was superior. The average reimbursement for hip arthroplasty at local hospitals was $50,000, while the average payment for outpatient resurfacing at our surgery center was $26,000. We conclude that outpatient hip resurfacing can be accomplished safely, with high patient satisfaction, and at a tremendous financial savings to the insurer/patient. LEVEL OF EVIDENCE: III.

Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.

Field-scale dispersal of Aphodius dung beetles (Coleoptera: Scarabaeidae) in response to avermectin treatments on pastured cattle.

Very few studies have examined, at the field scale, the potential for faecal residues in the dung of avermectin-treated cattle to affect dung-breeding insects. The current study examined populations of dung beetles (Scarabaeidae: Aphodius) using pitfall traps baited with dung from untreated cattle on 26 fields across eight farms in southwest Scotland. The fields were grazed either by untreated cattle or by cattle treated with an avermectin product, i.e. doramectin or ivermectin. During the two-year study, significantly more beetles were trapped in fields grazed by treated cattle (n=9377 beetles) than in fields where cattle remained untreated (n=2483 beetles). Additional trials showed that beetles preferentially colonised dung of untreated versus doramectin-treated cattle. This may explain the higher captures of beetles in traps baited with dung of untreated cattle, which were located in fields of treated cattle. Given that Aphodius beetles avoided dung of treated cattle in the current study, the potential harmful effects of avermectin residues in cattle dung could be reduced through livestock management practices that maximise the availability of dung from untreated livestock in areas where avermectins are being used.