The efficacy of teat sealants in dairy cows at dry-off to prevent new intra-mammary infections during the dry-period or clinical mastitis during early lactation: A protocol for a systematic review

Rationale: The majority of antibiotic use in the dairy industry is for intramammary infections (IMI), with a large portion of this aimed at treating and preventing IMI during the dry period (Lam et al., 2102). During dry off, formation of the teat-canal keratin plug plays an important role in susceptibility to IMI (Huxley et al., 2002), but there is wide variation between cows on time to complete closure of the teat-canal, or indeed if closure occurs at all (Dingwell et al., 2003). In heifers, pre-partum IMI is an important risk factor for the development of clinical mastitis in early lactation, and the impact of this disease on future udder health and productivity is far greater than in multiparous animals (Piepers et al., 2009). Moreover, the incidence of clinical mastitis at freshening in heifers is roughly double that of multiparous cows (Ali Naqvi et al., 2018). Teat sealants provide a non-antibiotic strategy to prevent IMI in the pre-calving period, which is of increasing importance due to concern for antimicrobial use and its relationship with the development of antimicrobial resistance (WHO, 2015). Understanding the efficacy of these products is essential to optimizing their use in order to decrease reliance on antibiotics for both treatment and prevention. Systematic reviews of randomized controlled trials in these areas will yield the highest level of evidence for efficacy of treatment under field conditions (Sargeant and O’Connor, 2014). Establishing the efficacy of teat sealants at dry-off, and pre-partum in heifers, to reduce the incidence of both clinical mastitis and/or IMI, will serve to improve decision makers’ ability to engage in effective stewardship of antibiotics thorough the strategic use of non-antibiotic alternatives

The efficacy of antibiotic treatments in dairy cows at dry-off to prevent new intramammary infections during the dry-period or clinical mastitis during early lactation: A protocol for a systematic review

Rationale: The majority of antibiotic use in the dairy industry is for the treatment and prevention of intramammary infections (IMI); in the Netherlands, approximately 60 % of all antimicrobial use in dairy is for this purpose, with two-thirds being dry cow therapy (Lam et al., 2012). In the United States, over 90 % of dairy cows receive dry cow therapy after every lactation (USDA-APHIS, 2016), with the goal of treating or preventing IMI during the dry period. These infections are strongly associated with risk of development of clinical mastitis in the first two weeks post-calving, which represents the highest risk period for this disease (Green et al., 2002). To combat this, blanket dry cow therapy (intramammary antimicrobial treatment of all quarters of all cows after the last milking of the lactation) was recommended for decades as part of a comprehensive strategy to reduce IMI in the dry period (Neave et al., 1969), and has been widely adopted in North America and the United Kingdom (Ruegg, 2017). Although cow2 level selective dry cow therapy has been in use in some regions for several decades (Schultze, 1983), interest has more recently increased worldwide, in part driven by concern for antimicrobial use and its relationship with the development of antimicrobial resistance between species (WHO, 2015), including nation-specific regulations (Santman-Berends et al., 2016). Selective dry cow therapy has been employed because it is a means to rapidly reduce the amount of antimicrobials used in dairy cattle (Vanhoudt et al., 2018), rather than because it is known to contribute importantly to antimicrobial resistance (Oliver et al., 2011). With a greater concern for prudent antibiotic use in the dairy industry, it is important that decision making with regards to dry cow therapy at both the cow and herd levels be evidencebased. Choosing ineffective antibiotics, or using antibiotic when not warranted, unnecessarily contributes to use while having little impact on controlling disease, which has substantial bearing to both profitability and animal welfare (Leslie & Petersson-Wolfe, 2012). Systematic reviews of randomized controlled trials yield the highest level of evidence for efficacy of treatment under field conditions (Sargeant and O’Connor, 2014), and comparative efficacy can be examined using network meta-analysis for multiple comparisons. Establishing the efficacy of both cow-level antibiotic therapy and herd-level dry cow antibiotic protocols for the prevention of IMI will serve to improve decision makers’ ability to engage in effective stewardship of antibiotics

Intrinsic Epithelial Cells Repair the Kidney after Injury

SummaryUnderstanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%–95% of tubular epithelial cells, but no interstitial cells, were labeled with either β-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney

Clostridium difficile PCR Ribotypes in Calves, Canada

C. difficile, including epidemic PCR ribotypes 017 and 027, were isolated from dairy calves in Canada

Clostridium difficile in Retail Ground Meat, Canada

Clostridium difficile was isolated from 12 (20%) of 60 retail ground meat samples purchased over a 10-month period in 2005 in Canada. Eleven isolates were toxigenic, and 8 (67%) were classified as toxinotype III. The human health implications of this finding are unclear, but with the virulence of toxinotype III strains further studies are required

Management of cull dairy cows—Consensus of an expert consultation in Canada

Many cull dairy cows enter the marketing system and travel to widely dispersed and specialized slaughter plants, and they may experience multiple handling events (e.g., loading, unloading, mixing), change of ownership among dealers, and feed and water deprivation during transport and at livestock markets. The objectives of this study were to describe the diverse management of cull dairy cows in Canada and establish consensus on ways to achieve improvements. A 2-day expert consultation meeting was convened, involving farmers, veterinarians, regulators, and experts in animal transport, livestock auction, and slaughter. The 15 participants, recruited from across Canada, discussed regional management practices for cull cattle, related risk factors, animal welfare problems, and recommendations. An audio recording of the meeting was used to extract descriptive data on cull cattle management and identify points of agreement. Eight consensus points were reached: (1) to assemble information on travel times and delays from farm to slaughter; (2) to increase awareness among producers and herd veterinarians of potential travel distances and delays; (3) to promote pro-active culling; (4) to improve the ability of personnel to assess animal condition before loading; (5) to identify local options for slaughter of cull dairy cows; (6) to investigate different management options such as emergency slaughter and mobile slaughter; (7) to ensure that all farms and auctions have, or can access, personnel trained and equipped for euthanasia; and (8) to promote cooperation among enforcement agencies and wider adoption of beneficial regulatory options

The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise

Purpose This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Methods Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. Results At HT, FT, and ET, reductions in maximal voluntary force (MVC; −11, −20 and −27%, respectively, P ≤ 0.01), potentiated twitch force (−15, −23 and −23%, respectively, P < 0.05), voluntary activation (FT, −15 and ET, −18%, P ≤ 0.01), and voluntary activation measured with TMS (−11, −15 and −17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6–11%; ICC2,1 0.83–0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5–18%; ICC2,1 0.63–0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3–6%; ICC2,1 0.90–0.98). Conclusion Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease