Genotypic analysis of a localised hotspot of Pestivirus A (BVDV-1) infections in Northern Ireland.

BACKGROUND: Bovine viral diarrhoea (BVD) is caused by Pestivirus A and Pestivirus B. Northern Ireland (NI) embarked on a compulsory BVD eradication scheme in 2016, which continues to this day, so an understanding of the composition of the pestivirus genotypes in the cattle population of NI is required. METHODS: This molecular epidemiology study employed 5' untranslated region (5'UTR) genetic sequencing to examine the pestivirus genotypes circulating in samples taken from a hotspot of BVD outbreaks in the Enniskillen area in 2019. RESULTS: Bovine viral diarrhoea virus (BVDV)-1e (Pestivirus A) was detected for the first time in Northern Ireland, and at a high frequency, in an infection hotspot in Enniskillen in 2019. There was no evidence of infection with BVDV-2 (Pestivirus B), Border disease virus (pestivirus D) or HoBi-like virus/BVDV-3 (pestivirus H). LIMITATIONS: Only 5'UTR sequencing was used, so supplementary sequencing, along with phylogenetic trees that include all BVDV-1 genotype reference strains, would improve accuracy. Examination of farm locations and animal movement/trade is also required. CONCLUSIONS: Genotype BVDV-1e was found for the first time in Northern Ireland, indicating an increase in the genetic diversity of BVDV-1, which could have implications for vaccine design and highlights the need for continued pestivirus genotypic surveillance.

A scoping review on bovine tuberculosis highlights the need for novel data streams and analytical approaches to curb zoonotic diseases.

Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a "virtuous cycle" of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.

Modelling dynamics between free-living amoebae and bacteria.

Free-living amoebae (FLA) serve as hosts for a variety of endosymbionts, which are microorganisms that reside and multiply within the FLA. Some of these endosymbionts pose a pathogenic threat to humans, animals, or both. The symbiotic relationship with FLA not only offers these microorganisms protection but also enhances their survival outside their hosts and assists in their dispersal across diverse habitats, thereby escalating disease transmission. This review is intended to offer an exhaustive overview of the existing mathematical models that have been applied to understand the dynamics of FLA, especially concerning their interactions with bacteria. An extensive literature review was conducted across Google Scholar, PubMed, and Scopus databases to identify mathematical models that describe the dynamics of interactions between FLA and bacteria, as published in peer-reviewed scientific journals. The literature search revealed several FLA-bacteria model systems, including Pseudomonas aeruginosa, Pasteurella multocida, and Legionella spp. Although the published mathematical models account for significant system dynamics such as predator-prey relationships and non-linear growth rates, they generally overlook spatial and temporal heterogeneity in environmental conditions, such as temperature, and population diversity. Future mathematical models will need to incorporate these factors to enhance our understanding of FLA-bacteria dynamics and to provide valuable insights for future risk assessment and disease control measures.

Antimicrobial resistance in Escherichia coli isolated from pigs and associations with aggregated antimicrobial usage in Ireland: A herd-level exploration.

AIMS: Antimicrobial resistance (AMR) is of significant global concern and is a major One Health issue. There is evidence to suggest that increased antimicrobial usage (AMU) can be associated with AMR patterns, and therefore, there have been efforts to reduce AMU in anticipation of reducing AMR emergence risk. The aim of this study was to investigate whether there were any associations between AMU and AMR patterns of commensal Escherichia coli isolated from pig herds in Ireland. METHODS AND RESULTS: Data on AMR from a panel of antimicrobials (AMDs) were gathered as part of national surveillance activities. These data were associated with reported usage of AMDs, on a year-quarter basis, measured in mg/kg at a herd-level using generalized estimating equation regression analysis. Associations were tested with AMR presence or multi-drug resistance (MDR; ≥3 classes) profiles and total AMU during the contemporaneous quarter and previous quarter, respectively. Furthermore, individual and AMD class-based associations were tested. The final dataset contained 218 observations (herd-quarter usage and AMR resistance profile) from 122 herds during 2019-2021. Apparent resistance prevalence varied according to AMD type, with the highest mean prevalence found with tetracycline at 51.57% (95% CI: 45.06%-58.09%). There were significant associations between a herd obtaining a positive AMR result for any AMDs and the overall levels of AMU during the year-quarter. Furthermore, there were significant positive associations between MDR and total AMU. At the compound level, chloramphenicol resistance was significantly associated with increased usage of trimethoprim/sulfadiazine and chlortetracycline, respectively (p < 0.010). Tetracycline resistance was associated with increased use of chlortetracycline (p = 0.008). At the antimicrobial class level, there was a significant positive relationship between the usage of phenicol and the probability of a resistance for chloramphenicol (p = 0.026) and between the usage of tetracycline and tetracycline resistance probability (p = 0.018). CONCLUSIONS: Our data provide evidence of associations between overall AMU and AMR or MDR risk at the herd-quarter level. There was also evidence of associations between specific AMDs and patterns of resistance. Associations varied depending on whether time lags in usage were modelled or how usage was modelled (e.g. dichotomized or continuous). Associations with rarely used AMDs (e.g. critically important AMDs) were precluded due to a lack of statistical power. Continued monitoring of both AMU and AMR is crucial to assess the impacts of policy changes aimed at reducing AMU.

Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt's Lymphoma (BL).

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry-Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i-19m were found to elicit potent antiproliferative effects in both BL cell lines EBV-MUTU-1 (chemosensitive) and EBV+ DG-75 (chemoresistant) with >90% inhibition at 10 µM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC50 values of 0.17 µM (HG-3) and 1.3 µM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL.

Across-country genetic and genomic analyses of foot score traits in American and Australian Angus cattle.

BACKGROUND: Hoof structure and health are essential for the welfare and productivity of beef cattle. Therefore, we assessed the genetic and genomic background of foot score traits in American (US) and Australian (AU) Angus cattle and investigated the feasibility of performing genomic evaluations combining data for foot score traits recorded in US and AU Angus cattle. The traits evaluated were foot angle (FA) and claw set (CS). In total, 109,294 and ~ 1.12 million animals had phenotypic and genomic information, respectively. Four sets of analyses were performed: (1) genomic connectedness between US and AU Angus cattle populations and population structure, (2) estimation of genetic parameters, (3) single-step genomic prediction of breeding values, and (4) single-step genome-wide association studies for FA and CS. RESULTS: There was no clear genetic differentiation between US and AU Angus populations. Similar heritability estimates (FA: 0.22-0.24 and CS: 0.22-0.27) and moderate-to-high genetic correlations between US and AU foot scores (FA: 0.61 and CS: 0.76) were obtained. A joint-genomic prediction using data from both populations outperformed within-country genomic evaluations. A genomic prediction model considering US and AU datasets as a single population performed similarly to the scenario accounting for genotype-by-environment interactions (i.e., multiple-trait model considering US and AU records as different traits), even though the genetic correlations between countries were lower than 0.80. Common significant genomic regions were observed between US and AU for FA and CS. Significant single nucleotide polymorphisms were identified on the Bos taurus (BTA) chromosomes BTA1, BTA5, BTA11, BTA13, BTA19, BTA20, and BTA23. The candidate genes identified were primarily from growth factor gene families, including FGF12 and GDF5, which were previously associated with bone structure and repair. CONCLUSIONS: This study presents comprehensive population structure and genetic and genomic analyses of foot scores in US and AU Angus cattle populations, which are essential for optimizing the implementation of genomic selection for improved foot scores in Angus cattle breeding programs. We have also identified candidate genes associated with foot scores in the largest Angus cattle populations in the world and made recommendations for genomic evaluations for improved foot score traits in the US and AU.

The Irish bTB eradication programme: combining stakeholder engagement and research-driven policy to tackle bovine tuberculosis.

A new Irish bovine tuberculosis (bTB) eradication strategy was launched in 2021. The strategy was formulated following extensive discussions with stakeholders, formal reviews of several aspects of the existing bTB policy and relevant inputs from the latest scientific research projects. A stakeholder discussion body, the TB Forum, had been established in 2018 and this continues under the new strategy, supported by three working groups (scientific, financial and implementation). The strategy sets out actions to address cattle-to-cattle and badger-to-cattle bTB transmission, along with actions to improve farm biosecurity and empower farmers to make their own choices to reduce bTB risk.Large scale vaccination of badgers has been rolled out under the new strategy, with over 20,000 km2 covered by the vaccination programme and 6,586 badgers captured in vaccination areas in 2021. Vaccination efforts have been complemented by intensive communications campaigns, including a web enabled software application ("app") enabling farmers to report the location of badger setts.Cattle which test inconclusive to the tuberculin skin test have been re-tested using a gamma interferon blood test since April 2021, enabling truly infected cattle to be identified more effectively due to the higher sensitivity of this test. An enhanced oversight process has been put in place for herds experiencing extended or repeat bTB breakdowns. Whole genome sequencing is being used to investigate links between breakdowns, with the results supporting operational decision making in case management.Communications, including biosecurity advice, are co-designed with stakeholders, in order to improve their effectiveness. A programme involving veterinary practitioners providing tailored biosecurity bTB advice to their clients was established in 2021 and was rolled out nationally during 2022.A core element of the new strategy is the continual improvement of policies in response to changing bTB risks, informed by scientific research and then implemented with stakeholder consultation.

Individual differences in speech-on-speech masking are correlated with cognitive and visual task performance.

Individual differences in spatial tuning for masked target speech identification were determined using maskers that varied in type and proximity to the target source. The maskers were chosen to produce three strengths of informational masking (IM): high [same-gender, speech-on-speech (SOS) masking], intermediate (the same masker speech time-reversed), and low (speech-shaped, speech-envelope-modulated noise). Typical for this task, individual differences increased as IM increased, while overall performance decreased. To determine the extent to which auditory performance might generalize to another sensory modality, a comparison visual task was also implemented. Visual search time was measured for identifying a cued object among "clouds" of distractors that were varied symmetrically in proximity to the target. The visual maskers also were chosen to produce three strengths of an analog of IM based on feature similarities between the target and maskers. Significant correlations were found for overall auditory and visual task performance, and both of these measures were correlated with an index of general cognitive reasoning. Overall, the findings provide qualified support for the proposition that the ability of an individual to solve IM-dominated tasks depends on cognitive mechanisms that operate in common across sensory modalities.

Inferring bovine tuberculosis transmission between cattle and badgers via the environment and risk mapping.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is one of the most challenging and persistent health issues in many countries worldwide. In several countries, bTB control is complicated due to the presence of wildlife reservoirs of infection, i.e. European badger (Meles meles) in Ireland and the UK, which can transmit infection to cattle. However, a quantitative understanding of the role of cattle and badgers in bTB transmission is elusive, especially where there is spatial variation in relative density between badgers and cattle. Moreover, as these two species have infrequent direct contact, environmental transmission is likely to play a role, but the quantitative importance of the environment has not been assessed. Therefore, the objective of this study is to better understand bTB transmission between cattle and badgers via the environment in a spatially explicit context and to identify high-risk areas. We developed an environmental transmission model that incorporates both within-herd/territory transmission and between-species transmission, with the latter facilitated by badger territories overlapping with herd areas. Model parameters such as transmission rate parameters and the decay rate parameter of M. bovis were estimated by maximum likelihood estimation using infection data from badgers and cattle collected during a 4-year badger vaccination trial. Our estimation showed that the environment can play an important role in the transmission of bTB, with a half-life of M. bovis in the environment of around 177 days. Based on the estimated transmission rate parameters, we calculate the basic reproduction ratio (R) within a herd, which reveals how relative badger density dictates transmission. In addition, we simulated transmission in each small local area to generate a first between-herd R map that identifies high-risk areas.

Trends and factors associated with dairy calf early slaughter in Ireland, 2018-2022.

Dairy systems require that each cow calves annually to have an efficient milk production cycle. In systems where milk production is maximized, the male offspring from dairy breed sires tend to have poor beef production traits and, therefore, can be of low economic value. Few studies have been published on the factors impacting early slaughtering of calves in peer-reviewed literature. Here we present an analysis of national data on calves slaughtered from 2018 to 2022 in Ireland. Data (Jan 2018-May 2022) on all cattle <6 months of age were collated at a national level and were described at calf-, herd-, and county-levels. These data were statistically analyzed at per-capita slaughter rates (calves/calf born) using negative binomial regression models with an offset. There were 125,260 calves slaughtered early (1.09% of total births) recorded in the dataset from 1,364 birth herds during the study period, of which 94.8% (118,761) were male. 51.7% were classified as Friesian-cross (FRX), 11.5% Friesian (FR) and 32.1% Jersey-cross (JEX). The median age at slaughter was 16 days (Mean: 18.9 days; IQR: 13-22). The median calves/herd slaughtered was 16 (mean: 91.8); median calves/herd/year slaughtered was 21 (mean: 42.0). There was substantial variation in counts of calves slaughtered across herds, years, and counties. Herd calf slaughter rates and per capita calf slaughter rates increased significantly in 2022, with the highest rates over the time series. Calf slaughter rates varied significantly with herd size, year, and major breed (Jersey; JE). Herds which were more recently established tended to have higher calf slaughter rates. Herds that repeatedly slaughtered calves over 2 or more years tended to be larger and slaughtered more calves/herd/year. The slaughtering of calves is not widespread across the dairy industry in Ireland. The distribution of calves slaughtered per herd demonstrate that a small number of herds contributed disproportionately to calf slaughter numbers. Such herds tended to be very large (herd size), more recently established (2016 onwards), and have higher proportions of JE/JEX breed cattle. The outcomes of the present study provide an evidential base for the development of targeted industry-lead interventions with the aim of ending the routine early slaughter of calves.

Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland.

Bovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Lack of understanding of transmission dynamics may undermine eradication efforts. Pathogen whole-genome sequencing improves epidemiological inferences, providing a means to determine the relative importance of inter- and intra-species host transmission for disease persistence. We sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100 km2 bTB 'hotspot' in Northern Ireland. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided a unique opportunity to study disease transmission dynamics in unparalleled detail. Additionally, to assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. Birth death models and TransPhylo analyses indicated that cattle were likely driving the local epidemic, with transmission from cattle to badgers being more common than badger to cattle. Furthermore, the presence of significant badger population genetic structure in the landscape was not associated with the spatial distribution of M. bovis genetic diversity, suggesting that badger-to-badger transmission is not playing a major role in transmission dynamics. Our data were consistent with badgers playing a smaller role in transmission of M. bovis infection in this study site, compared to cattle. We hypothesize, however, that this minor role may still be important for persistence. Comparison to other areas suggests that M. bovis transmission dynamics are likely to be context dependent, with the role of wildlife being difficult to generalize.

A new subgenus, Australixodes n. subgen. (Acari: Ixodidae), for the kiwi tick, Ixodes anatis Chilton, 1904, and validation of the subgenus Coxixodes Schulze, 1941 with a phylogeny of 16 of the 22 subgenera of Ixodes Latreille, 1795 from entire mitochondrial genome sequences.

A new subgenus, Australixodes n. subgen., is described for the kiwi tick, Ixodes anatis Chilton, 1904. The subgenus Coxixodes Schulze, 1941 is validated for the platypus tick, Ixodes (Coxixodes) ornithorhynchi Lucas, 1846, sister group of the subgenus Endopalpiger Schulze, 1935. A phylogeny from mitochondrial genomes of 16 of the 22 subgenera of Ixodes (32 spp.) indicates, for the first time, the relationships of the subgenera of Ixodes Latreille, 1795, the largest genus of ticks.

Bovine tuberculosis in youngstock cattle: A narrative review.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a high-priority global pathogen of concern. The role of youngstock animals in the epidemiology of bTB has not been a focus of contemporary research. Here we have aimed to collate and summarize what is known about the susceptibility, diagnosis, transmission (infectiousness), and epidemiology to M. bovis in youngstock (up to 1-year of age). Youngstock are susceptible to M. bovis infection when exposed, with the capacity to develop typical bTB lesions. Calves can be exposed through similar routes as adults, via residual infection, contiguous neighborhood spread, wildlife spillback infection, and the buying-in of infected but undetected cattle. Dairy systems may lead to greater exposure risk to calves relative to other production systems, for example, via pooled milk. Given their young age, calves tend to have shorter bTB at-risk exposure periods than older cohorts. The detection of bTB varies with age when using a wide range of ante-mortem diagnostics, also with post-mortem examination and confirmation (histological and bacteriological) of infection. When recorded as positive by ante-mortem test, youngstock appear to have the highest probabilities of any age cohort for confirmation of infection post-mortem. They also appear to have the lowest false negative bTB detection risk. In some countries, many calves are moved to other herds for rearing, potentially increasing inter-herd transmission risk. Mathematical models suggest that calves may also experience lower force of infection (the rate that susceptible animals become infected). There are few modeling studies investigating the role of calves in the spread and maintenance of infection across herd networks. One study found that calves, without operating testing and control measures, can help to maintain infection and lengthen the time to outbreak eradication. Policies to reduce testing for youngstock could lead to infected calves remaining undetected and increasing onwards transmission. Further studies are required to assess the risk associated with changes to testing policy for youngstock in terms of the impact for within-herd disease control, and how this may affect the transmission and persistence of infection across a network of linked herds.

Revisiting the relative effectiveness of slaughterhouses in Ireland to detect tuberculosis lesions in cattle (2014-2018).

Slaughterhouse or meat factory surveillance to detect factory lesions (FL) at slaughter is an important part of the bovine tuberculosis (bTB) eradication program in Ireland. The objective of this study was to quantify the effectiveness of Irish slaughterhouses or factories in submitting FL and the proportion of those submitted FL confirmed as being due to bTB in slaughtered cattle, and to identify and quantify the association of risk factors at animal, herd, and factory level with FL submission and confirmation. The data consisted of 6,611,854 animals slaughtered in Irish factories from 2014 to 2018 obtained from the Department of Agriculture, Food and Marine (DAFM), Ireland. Selected risk factors for this study included factory, year and month of slaughter, age, sex, breed, animal movement, ever inconclusive in the standard or severe skin test, herd type, herd size, and bTB history. The association of each risk factor on the FL submission and confirmation risk were analysed with univariable followed by a multivariable logistic regression with herd as random effect. Factories were ranked and compared based on the odds ratio (OR) obtained from the univariable (crude OR) and multivariable (adjusted OR) analysis. The average submission risk of all factories was 20 per 10,000 animals slaughtered, ranging from 1 to 42 per 10,000 animals slaughtered, and the average confirmation risk over all factories was 40.72%, ranging from 0.00 to 61.84%. The odds of submitting and confirming FL as bTB positive were higher in animals over eight years old compared to animals 1-2 years old (OR = 1.91, 95 CI 95% 1.77-2.06 and OR = 4.05, 95% CI 3.17-5.18, respectively), and were higher in animals that ever had inconclusive skin result based on severe interpretation (OR = 2.83, 95% CI 2.44-3.27 and OR = 4.48, 95% CI 2.66-7.54, respectively), animals originating from sucklers herds (OR = 1.08, 95% CI 1.02-1.14 and OR = 1.31, 95% CI 1.11-1.55, respectively), or herds with bTB history in the past three years (OR = 4.46, 95% CI 4.28-4.66 and OR = 319.90, 95% CI 237.98-430.04, respectively). The odds of FL submission and confirmation decreased as the herd size increased (OR = 0.95, 95% CI 0.93-0.96 and OR = 0.82, 95% CI 0.78-0.86, respectively). An inverse relationship of FL submission and confirmation was present for variable sex and inconclusive skin result with standard interpretation, where submission odds were higher in males (OR = 1.05, 95% CI 1.00-1.10) and ever inconclusive animals (OR = 74.24, 95% CI 69.39-79.43), although the confirmation odds were lower (males OR = 0.66, 95% CI 0.56-0.76; ever inconclusive OR = 0.44, 95% CI 0.36-0.54). The crude and adjusted ranking of factories did not differ greatly for FL submission, indicating that factory-related factors may contribute significantly to the submission variation between factories. However, a substantial difference between crude and adjusted confirmation ranking was present which may indicate that animal and herd-related factors were associated to variation in confirmation risk between factories.

Can more information be extracted from bovine TB skin test outcomes to inform animal risk management? A retrospective observational animal-level study.

Continual tailoring of control programmes of endemic pathogens during long-term eradication campaigns requires detailed analysis of surveillance data to inform evidence-based policy. Bovine tuberculosis is a disease where long-term control and eradication programs are in train in several countries. The primary diagnostic tool, the intradermal tuberculin test, used to identify infected animals can be interpreted using different criteria and cut-offs, facilitating flexibility in its use as a basis to inform interventions. We investigated the comparative risk of animals failing a single intradermal comparative tuberculin test (SICTT) based on their previous tuberculin test result following a higher risk test-type (reactor retest of an infected herd). The study was a retrospective cohort design, and the primary exposure was the test status following a reactor retest classified as mutually exclusive categories based on bovine and avian tuberculin reactions: standard interpretation inconclusive (Sdi), severe interpretation inconclusive (Svi), single intradermal test (SIT) reactors (SITr), SIT inconclusive (SITi), avian tuberculin reactors (Ar), and test negative animals. Random effects multivariable logistic regression was used to investigate future risk. Cross-validation and downscaling was used to explore model performance. Alternate models with differing outcome test types were also explored. The models were trained on 844,207 observations from June 2018 to June 2021. Sdi, Svi, SITr, SITi and Ar were associated with the following odds ratios 12.242 (95 %CIs: 5.236-28.625; p < 0.001), 4.101 (95 %CIs: 3.423-4.913; p < 0.001), 2.503 (95 %CIs: 1.878-3.338; p < 0.001), 1.741 (95 %CIs: 1.195-2.538; p = 0.004) and 1.065 (95 %CIs: 0.833-1.361; p = 0.616) for failing the next test, respectively. High model performance was achieved with inclusion of random effects for both training and test evaluation datasets (AUC: 0.94; Balanced accuracy: 0.84), but fixed-effects only predictions exhibited moderate performance (AUC: 0.70; Balanced accuracy: 0.69). This reflects that 55 % of the risk of test failure relates to between herd heterogeneity based on intra-class correlation, while controlling for fixed effects. Other factors that were associated with increasing risk included age (older cohorts were at greater risk than the youngest cohort), breakdown history of the herd (greater number of breakdowns prior to the study period), and the time between exposure test and outcome test. These results provide further evidence to inform risk-based management policies for TB, including the removal of Sdi animals in higher risk situations, supplementary testing of cattle based on tuberculin responses and the provision of risk management advice to herd owners. The results characterise the future animal-level risk posed by Svis and suggest this risk may require policy led interventions.

Disturbance Ecology Meets Bovine Tuberculosis (bTB) Epidemiology: A Before-and-After Study on the Association between Forest Clearfelling and bTB Herd Risk in Cattle Herds.

Disturbance ecology refers to the study of discrete processes that disrupt the structure or dynamics of an ecosystem. Such processes can, therefore, affect wildlife species ecology, including those that are important pathogen hosts. We report on an observational before-and-after study on the association between forest clearfelling and bovine tuberculosis (bTB) herd risk in cattle herds, an episystem where badgers (Meles meles) are the primary wildlife spillover host. The study design compared herd bTB breakdown risk for a period of 1 year prior to and after exposure to clearfelling across Ireland at sites cut in 2015-2017. The percent of herds positive rose from 3.47% prior to clearfelling to 4.08% after exposure. After controlling for confounders (e.g., herd size, herd type), we found that cattle herds significantly increased their odds of experiencing a bTB breakdown by 1.2-times (95%CIs: 1.07-1.36) up to 1 year after a clearfell risk period. Disturbance ecology of wildlife reservoirs is an understudied area with regards to shared endemic pathogens. Epidemiological observational studies are the first step in building an evidence base to assess the impact of such disturbance events; however, such studies are limited in inferring the mechanism for any changes in risk observed. The current cohort study suggested an association between clearfelling and bTB risk, which we speculate could relate to wildlife disturbance affecting pathogen spillback to cattle, though the study design precludes causal inference. Further studies are required. However, ultimately, integration of epidemiology with wildlife ecology will be important for understanding the underlying mechanisms involved, and to derive suitable effective management proposals, if required.

BVD seroprevalence in the Irish cattle population as the national BVD programme progresses toward eradication.

BACKGROUND: Bovine Viral Diarrhoea Virus (BVDV) infection remains endemic in many countries worldwide. Ireland, in common with several other European counties, commenced an BVDV eradication programme in the last decade, Managing eradication programmes requires careful monitoring of diseases prevalence and understanding factors associated with disease exposure to ensure eradication programmes remain evidence based and tailored to the evolving epidemiological situation. METHODS: In this study, we explore the seroprevalence of BVDV exposure over a four-year period (2017 to 2020) in Ireland from a cohort of animals (n = 6,449) under 30 months of age sampled at slaughter, who were born subsequent to the commencement of a compulsory national eradication programme. Temporal trends and risk factor analysis were undertaken using multilevel logit regression models. RESULTS: There was a declining temporal trend in seroprevalence over the sample years of the study, and risk varied at both county- and herd-levels. The unadjusted marginal animal-level seroprevalence reduced from 9.1% in 2017 (95%; CI: 7.2-10.9) to 3.9% in 2020 (95%; CI: 3.2-4.6). The final model suggested that seropositivity in study cattle was strongly related with the presence of a PI animal in the herd during the year of the animal's birth, and to a lesser extent the status of the herd from which the animal was slaughtered. The risk of seroconversion increased significantly with increasing size of the herd of slaughter, in females relative to males, and in dairy relative to suckler herds. CONCLUSIONS: This study has shown that the BVDV serostatus of cattle at slaughter is correlated to the BVD infection history of the herd into which the animal was born and the herd from which it was slaughtered. Herd location, increased herd size and dairy production were associated with increased probability of serconversion. These findings will be used to inform the targeting of surveillance strategies once BVDV freedom has been achieved.

Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations.

The recent interest in advanced biologic therapies in veterinary medicine has opened up opportunities for new treatment modalities with considerable clinical potential. Studies with mesenchymal stromal cells (MSCs) from animal species have focused on in vitro characterization (mostly following protocols developed for human application), experimental testing in controlled studies and clinical use in veterinary patients. The ability of MSCs to interact with the inflammatory environment through immunomodulatory and paracrine mechanisms makes them a good candidate for treatment of inflammatory musculoskeletal conditions in canine species. Analysis of existing data shows promising results in the treatment of canine hip dysplasia, osteoarthritis and rupture of the cranial cruciate ligament in both sport and companion animals. Despite the absence of clear regulatory frameworks for veterinary advanced therapy medicinal products, there has been an increase in the number of commercial cell-based products that are available for clinical applications, and currently the commercial use of veterinary MSC products has outpaced basic research on characterization of the cell product. In the absence of quality standards for MSCs for use in canine patients, their safety, clinical efficacy and production standards are uncertain, leading to a risk of poor product consistency. To deliver high-quality MSC products for veterinary use in the future, there are critical issues that need to be addressed. By translating standards and strategies applied in human MSC manufacturing to products for veterinary use, in a collaborative effort between stem cell scientists and veterinary researchers and surgeons, we hope to facilitate the development of quality standards. We point out critical issues that need to be addressed, including a much higher level of attention to cell characterization, manufacturing standards and release criteria. We provide a set of recommendations that will contribute to the standardization of cell manufacturing methods and better quality assurance.

The Effect of Vocational Counseling Interventions for Adults with Substance Use Disorders: A Narrative Review.

The authors reviewed the research literature evaluating the effectiveness of vocational counseling interventions focused on employment for consumers with substance use disorders. This review included 11 articles related to vocational counseling interventions, which are either incorporated with substance use treatment or not. The results of this review revealed that vocational counseling services have been highly efficacious in resulting in part-time and full-time jobs. The study designs had some limitations, and few studies employed randomized control trials (RCT).

Forward masking of spectrotemporal modulation detection.

Recent work has suggested that there may be specialized mechanisms in the auditory system for coding spectrotemporal modulations (STMs), tuned to different combinations of spectral modulation frequency, temporal modulation frequency, and STM sweep direction. The current study sought evidence of such mechanisms using a psychophysical forward masking paradigm. The detectability of a target comprising upward sweeping STMs was measured following the presentation of modulated maskers applied to the same carrier. Four maskers were tested, which had either (1) the same spectral modulation frequency as the target but a flat temporal envelope, (2) the same temporal modulation frequency as the target but a flat spectral envelope, (3) the same spectral and temporal modulation frequencies as the target but the opposite sweep direction (downward sweeping STMs), or (4) the same spectral and temporal modulation frequencies as the target and the same sweep direction (upward sweeping STMs). Forward masking was greatest for the masker fully matched to the target (4), intermediate for the masker with the opposite sweep direction (3), and negligible for the other two (1, 2). These findings are consistent with the suggestion that the detectability of the target was mediated by an STM-specific coding mechanism with sweep-direction selectivity.