The use of a cephalonium containing dry cow therapy and an internal teat sealant, both alone and in combination

AbstractThe dry period is a critical time in the lactation cycle, being the optimum time to cure existing intramammary infection (IMI) as well as encompassing the periods of highest susceptibility to new infection. Currently, IMI in the dry period is controlled with antibiotic dry cow therapy. The aim of this randomized control trial was to investigate different dry cow therapy regimens by stratifying cows by likely infection status at drying off in herds with low somatic cell count (SCC; bulk milk SCC <250,000 cells/mL) in southwest England. All quarters in 890 cows were recruited. The recruited cows were categorized as either infected or uninfected on the basis of SCC and clinical mastitis history. Ipsilateral quarters within each cow were randomly allocated to receive 1 of 4 different treatment regimens according to their infection category. Quarters in high-SCC infected cows were allocated to receive antibiotic dry cow therapy either alone or in combination with an internal teat sealant; quarters in low-SCC uninfected cows were allocated to receive teat sealant either alone or in combination with antibiotic dry cow therapy. All quarters were sampled for bacteriology at drying off and again within 10 d post-calving. Quarters were subsequently monitored for clinical mastitis for the first 100 d of lactation. The mass of residual sealant was assessed immediately post-calving to allow assessment of the association of sealant retention with treatment efficacy. Models were constructed to assess the efficacy of the different regimens in preventing IMI. Apparent cure rates of existing IMI with major pathogens were consistently >90% in quarters receiving antibiotic. Combination treatment of high-SCC infected cows resulted in an increased likelihood of being pathogen free post-calving (odds ratio=1.40; 95% credibility interval=1.03–1.90). The benefits of combination treatment of low-SCC uninfected cows were less clear. With respect to clinical mastitis, combination treatment of high-SCC infected cows resulted in a decreased likelihood of developing clinical mastitis in the first 100 d of the subsequent lactation (odds ratio=0.68; 95% credibility interval=0.48–0.98). The retention of the internal sealant was adversely affected by its use in combination with antibiotic dry cow therapy

Randomized controlled field trial comparing quarter and cow level selective dry cow treatment using the California Mastitis Test

Selective use of antibiotic dry cow treatment can be implemented at the cow or quarter level, with the latter having the potential to further reduce antibiotic use. Our objective was to compare these 2 approaches in 6 herds in the United Kingdom in which environmental mastitis predominated. Eight hundred seven cows were enrolled and categorized as having a high cell count (n = 401) or low cell count (n = 406) in the last 3 mo of lactation and clinical mastitis history. All quarters of all enrolled cows received an internal teat sealant. Within each category, cows were randomly allocated to 1 of 3 groups; in one group antibiotic treatment was allocated at cow level (i.e., all 4 quarters received antibiotic), whereas in the 2 remaining groups antibiotic treatment was allocated at quarter level, based on California Mastitis Test (CMT) findings. Two different thresholds, score 1 and 2, were used to determine likely infection status. Quarter milk samples were collected at dry off and postcalving for bacteriological culture and somatic cell count (SCC). Cows were monitored for clinical mastitis from dry off until 100 d in milk. Cow level SCC and milk yield data were collated from farm records. Within each category, the 2 quarter level treatment groups were compared with cow level treatment at dry off. Leaving quarters untreated with intramammary antibiotic in cows in the high cell count group, with a CM

Factors affecting the cost-effectiveness of on-farm culture prior to the treatment of clinical mastitis in dairy cows

The objective of this study was to use probabilistic sensitivity analysis to evaluate the cost-effectiveness of using an on-farm culture (OFC) approach to the treatment of clinical mastitis in dairy cows and compare this to a ‘standard’ treatment approach. A specific aim was to identify the herd circumstances under which an OFC approach would be most likely to be cost-effective. A stochastic Monte Carlo model was developed to simulate 5000 cases of clinical mastitis at the cow level and to calculate the associated costs simultaneously when treated according to 2 different treatment protocols; i) a 'conventional' approach (3 tubes of intramammary antibiotic) and ii) an OFC programme, whereby cows are treated according to the results of OFC. Model parameters were taken from recent peer reviewed literature on the use of OFC prior to treatment of clinical mastitis. Spearman rank correlation coefficients were used to evaluate the relationships between model input values and the estimated difference in cost between the standard and OFC treatment protocols. The simulation analyses revealed that both the difference in the bacteriological cure rate due to a delay in treatment when using OFC and the proportion of Gram-positive cases that occur on a dairy unit would have a fundamental impact on whether OFC would be cost-effective. The results of this study illustrated that an OFC approach for the treatment of clinical mastitis would probably not be cost-effective in many circumstances, in particular, not those in which Gram-positive pathogens were responsible for more than 20% of all clinical cases. The results highlight an ethical dilemma surrounding reduced use of antimicrobials for clinical mastitis since it may be associated with financial losses and poorer cow welfare in many instances

L-infinity algebra connections and applications to String- and Chern-Simons n-transport

We give a generalization of the notion of a Cartan-Ehresmann connection from Lie algebras to L-infinity algebras and use it to study the obstruction theory of lifts through higher String-like extensions of Lie algebras. We find (generalized) Chern-Simons and BF-theory functionals this way and describe aspects of their parallel transport and quantization. It is known that over a D-brane the Kalb-Ramond background field of the string restricts to a 2-bundle with connection (a gerbe) which can be seen as the obstruction to lifting the PU(H)-bundle on the D-brane to a U(H)-bundle. We discuss how this phenomenon generalizes from the ordinary central extension U(1) -> U(H) -> PU(H) to higher categorical central extensions, like the String-extension BU(1) -> String(G) -> G. Here the obstruction to the lift is a 3-bundle with connection (a 2-gerbe): the Chern-Simons 3-bundle classified by the first Pontrjagin class. For G = Spin(n) this obstructs the existence of a String-structure. We discuss how to describe this obstruction problem in terms of Lie n-algebras and their corresponding categorified Cartan-Ehresmann connections. Generalizations even beyond String-extensions are then straightforward. For G = Spin(n) the next step is "Fivebrane structures" whose existence is obstructed by certain generalized Chern-Simons 7-bundles classified by the second Pontrjagin class.Comment: 100 pages, references and clarifications added; correction to section 5.1 and further example to 9.3.1 adde

An investigation of the efficacy of a polyvalent mastitis vaccine using different vaccination regimens under field conditions in the United Kingdom

Vaccination can play a useful role in mastitis control programs, although there is a relative dearth of large, well-controlled field efficacy studies. This paper presents the findings on the use of a commercially available vaccine (Startvac, Hipra UK Ltd., Nottingham, UK) on commercial units under UK field conditions. In total, 3,130 cows were recruited from 7 farms and were randomly allocated, within farm, to 1 of 3 groups. The first group received the vaccine following the label regimen, the second group was vaccinated every 90 d following an initial vaccination course, and the third group was left unvaccinated to act as controls. Vaccine efficacy was assessed in the first 120 d of lactation. Data were available for analysis from 1,696 lactations in 1,549 cows. In total, 779 cases of clinical mastitis occurred in the 3 study groups, and we detected no significant difference in the incidence or prevalence of clinical or subclinical mastitis between any of the 3 groups. Mastitis vaccination following the label regimen was associated with a significant reduction in the severity of clinical cases. Cows in this group were at significantly decreased odds of developing clinical mastitis presenting with more than just milk changes [odds ratio: 0.58; 95% confidence interval (CI): 0.35–0.98]. Similarly, each additional vaccination resulted in a cow being at decreased odds of developing clinical mastitis presenting with more than just milk changes (odds ratio: 0.87; 95% CI: 0.77–0.98). Although no cows were culled because of severe mastitis in either of the vaccinated groups, we detected no significant difference in the mastitis-related culling rate between groups. Analysis of milk production data demonstrated that, on average, cows on the label regimen produced a higher volume of milk (231 L; 95% CI: 104.1–357.4) and more milk solids (12.36 kg; 95% CI: 3.12–21.60) than unvaccinated cows in the first 120 d of lactation. Conservative analysis suggested that a return on investment of 2.57:1 could be expected under UK conditions based on increased milk yield alone

An investigation of the dynamics of intramammary infections acquired during the dry period on European dairy farms

The dry period is acknowledged as playing a key role in mastitis epidemiology and yet surprisingly few studies have explored dry period infection dynamics in detail. The aim of this study was to investigate the dynamics of intramammary infection across a cohort of dairy herds in Europe. Five hundred and twenty-two cows were recruited from 12 farms in 6 European countries. All cows received antibiotic dry cow therapy but teat sealants were not used. All quarters of all cows were sampled for bacteriology at drying off and in the week immediately postcalving. Two ipsilateral quarters were also sampled for bacteriology in each cow 2 and 6 wk after drying off. Cows were body condition scored and teats assessed for cleanliness at all sampling time points and for the presence of a keratin plug during the dry period. Other cow-level parameters such as historic somatic cell counts and milk yields before drying off were collated from farm records. Univariable and multivariable analyses were undertaken to investigate the etiology, prevalence, and dynamics of infection during the dry period and associated influential factors. In summary, environmental mastitis pathogens predominated. Although gram-positive major pathogens were typically well controlled and did not increase in prevalence across the dry period, gram-negative pathogens generally increased in prevalence. There was an increase in the number of quarters that yielded no growth across the dry period, although this was driven by minor rather than major mastitis pathogen control. Other than the presence of a gram-positive or gram-negative pathogen 6 wk after drying off, the measured parameters were not influential when considering their effect on the presence of pathogens postcalving. Analysis also suggested that the early and mid dry period may be more important with respect to the timing of acquisition of infection than previously thought. We observed substantial variation in the etiology and prevalence of different pathogens on different farms with, in all cases, at least one of the 12 herds experiencing the opposite of the others with respect to increases and decreases in pathogen prevalence. Overall, this study confirms the importance of the dry period in mastitis epidemiology but highlights the importance of assessing and understanding infection dynamics on individual units. The lack of influence of the cow and quarter factors measured in this study suggests that herd and management factors may be more influential

Rascall: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)

RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, integrating RNA-seq in a clinical setting requires rapid detection and accurate reporting of clinically relevant alterations. Here we present RaScALL, an implementation of the k-mer based variant detection tool km, capable of identifying more than 100 prognostically significant lesions observed in ALL, including gene fusions, single nucleotide variants and focal gene deletions. We compared genomic alterations detected by RaScALL and those reported by alignment-based de novo variant detection tools in a study cohort of 180 Australian patient samples. Results were validated using 100 patient samples from a published North American cohort. RaScALL demonstrated a high degree of accuracy for reporting subtype defining genomic alterations. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% of reported cases in the study cohort (n = 164) and 95% of samples (n = 63) in the validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n = 12) and IKZF1 p.N159Y (n = 4). Intragenic IKZF1 deletions resulting in aberrant transcript isoforms were also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches. The application of RaScALL enables rapid identification and reporting of previously identified genomic alterations of known clinical relevance.Jacqueline Rehn, Chelsea Mayoh, Susan L Heatley, Barbara J McClure, Laura N Eadie, Caitlin Schutz, David T Yeung, Mark J Cowley, James Breen, Deborah L Whit

Associations between udder health and reproductive performance in United Kingdom dairy cows

The objective of this research was to evaluate the relationship between udder health and reproductive performance in UK dairy cows. Data from 80 herds were restructured such that each unit of data represented a 2-d period during lactation where a cow was at risk of becoming pregnant. Multilevel discrete-time survival models were then used within a Bayesian framework to explore associations between reproductive outcomes and a variety of potential explanatory variables. Separate models were constructed using 2 different univariate binary outcomes: a cow becoming pregnant during a risk period and a cow becoming pregnant as a result of a given service. Potential explanatory variables included occurrence of clinical mastitis and a categorical representation of individual cow somatic cell count (SCC), both at a variety of timings relative to the risk period. Posterior predictions were used to assess model fit and to check model building assumptions. These demonstrated that the model represented the data well. Within-sample Monte Carlo simulation (i.e., use of the model to predict outcomes for cases within the data set, repeated over a large number of iterations) was used to illustrate results as posterior predicted relative risks. A negative association was found between reproductive performance and cases of clinical mastitis over a wide time frame relative to the risk period (from 28 d before to 70 d after the risk period). A similar negative association with the probability of a service leading to a pregnancy (pregnancy rate) was observed over the same time frame. Higher SCC recordings (i.e., those more likely to be associated with an intramammary infection) were also associated with decreased reproductive performance, especially where an individual cow SCC of greater than 399,000/mL was recorded in the 30 d following a risk period or service. This research demonstrates that both clinical and subclinical mastitis are associated with a reduction in reproductive performance, and that this influence varies in magnitude but can be exerted over a prolonged period

A Bayesian micro-simulation to evaluate the cost-effectiveness of interventions for mastitis control during the dry period in UK dairy herds

Importance of the dry period with respect to mastitis control is now well established although the precise interventions that reduce the risk of acquiring intramammary infections during this time are not clearly understood. There are very few intervention studies that have measured the clinical efficacy of specific mastitis interventions within a cost-effectiveness framework so there remains a large degree of uncertainty about the impact of a specific intervention and its costeffectiveness. The aim of this study was to use a Bayesian framework to investigate the cost-effectiveness of mastitis controls during the dry period. Data were assimilated from 77 UK dairy farms that participated in a British national mastitis control programme during 2009–2012 in which the majority of intramammary infections were acquired during the dry period. The data consisted of clinical mastitis (CM) and somatic cell count (SCC) records, herd management practices and details of interventions that were implemented by the farmer as part of the control plan. The outcomes used to measure the effectiveness of the interventions were i) changes in the incidence rate of clinical mastitis during the first 30 days after calving and ii) the rate at which cows gained new infections during the dry period (measured by SCC changes across the dry period from 200,000 cells/ml). A Bayesian one-step microsimulation model was constructed such that posterior predictions from the model incorporated uncertainty in all parameters. The incremental net benefit was calculated across 10,000 Markov chain Monte Carlo iterations, to estimate the cost-benefit (and associated uncertainty) of each mastitis intervention. Interventions identified as being cost-effective in most circumstances included selecting dry-cow therapy at the cow level, dry-cow rations formulated by a qualified nutritionist, use of individual calving pens, first milking cows within 24 h of calving and spreading bedding evenly in dry-cow yards. The results of this study highlighted the efficacy of specific mastitis interventions in UK conditions which, when incorporated into a costeffectiveness framework, can be used to optimize decision making in mastitis control. This intervention study provides an example of how an intuitive and clinically useful Bayesian approach can be used to form the basis of an on-farm decision support tool

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure