Predicting lameness in dairy cattle using untargeted liquid chromatography-mass spectrometry-based metabolomics and machine learning.

Lameness in dairy cattle is a highly prevalent condition that impacts on the health and welfare of dairy cows. Prompt detection and implementation of effective treatment is important for managing lameness. However, major limitations are associated with visual assessment of lameness, which is the most commonly used method to detect lameness.

Longitudinal study of antimicrobial use patterns, vaccination and disease prevalence in British sheep flocks.

Background: The aim of the study was to describe the longitudinal dynamics of antimicrobial use (AMU) on sheep farms and explore associations between AMU and management factors, vaccination strategies, reproductive performance and prevalence of lameness.

Methods: Antimicrobial supply data were collected for 272 British sheep farms for 3-6 consecutive years between 2015 and 2021. These data were obtained from the farms' veterinary practices.

Metabolic alterations in dairy cattle with lameness revealed by untargeted metabolomics of dried milk spots using direct infusion-tandem mass spectrometry and the triangulation of multiple machine learning models.

Lameness is a major challenge in the dairy cattle industry in terms of animal welfare and economic implications. Better understanding of metabolic alteration associated with lameness could lead to early diagnosis and effective treatment, there-fore reducing its prevalence. To determine whether metabolic signatures associated with lameness could be discovered with untargeted metabolomics, we developed a novel workflow using direct infusion-tandem mass spectrometry to rapidly analyse (2 min per sample) dried milk spots (DMS) that were stored on commercially available Whatman® FTA® DMPK cards for a prolonged period (8 and 16 days).

The effect of environmental temperature on average daily gain in preweaned calves: A randomized controlled trial and Bayesian analysis.

Neonatal calves are relatively susceptible to heat loss, and previous research suggests that reduced environmental temperatures are associated with reduced average daily gain (ADG) during the preweaning phase. Current methods of mitigating negative effects of colder environmental conditions include the use of calf jackets and the provision of supplementary heat sources; however, previous research is limited. The aim of this study was to evaluate the effect of calf jackets and 1-kW heat lamps on the growth rates of preweaning calves and evaluate associations between environmental temperature and ADG using a Bayesian approach to incorporate both current and previous data.

Improving growth rates in preweaning calves on dairy farms: A randomized controlled trial.

Previous research has identified key factors associated with improved average daily gain (ADG) in preweaning dairy calves and these factors have been combined to create a web app-based calf health plan (www.nottingham.ac.

Factors associated with daily weight gain in preweaned calves on dairy farms.

The preweaning period is vital in the development of calves on dairy farms and improving daily liveweight gain (DLWG) is important to both financial and carbon efficiency; minimising rearing costs and improving first lactation milk yields. In order to improve DLWG, veterinary advisors should provide advice that has both a large effect size as well as being consistently important on the majority of farms. Whilst a variety of factors have previously been identified as influencing the DLWG of preweaned calves, it can be challenging to determine their relative importance, which is essential for optimal on-farm management decisions.

Quantitative Analysis of Colostrum Bacteriology on British Dairy Farms.

Total bacterial counts (TBC) and coliform counts (CC) were estimated for 328 colostrum samples from 56 British dairy farms. Samples collected directly from cows' teats had lower mean TBC (32,079) and CC (21) than those collected from both colostrum collection buckets (TBC: 327,879, CC: 13,294) and feeding equipment (TBC: 439,438, CC: 17,859). Mixed effects models were built using an automated backwards stepwise process in conjunction with repeated bootstrap sampling to provide robust estimates of both effect size and 95% bootstrap confidence intervals (BCI) as well as an estimate of the reproducibility of a variable effect within a target population (stability).

Automated prediction of mastitis infection patterns in dairy herds using machine learning.

Mastitis in dairy cattle is extremely costly both in economic and welfare terms and is one of the most significant drivers of antimicrobial usage in dairy cattle. A critical step in the prevention of mastitis is the diagnosis of the predominant route of transmission of pathogens into either contagious (CONT) or environmental (ENV), with environmental being further subdivided as transmission during either the nonlactating "dry" period (EDP) or lactating period (EL). Using data from 1000 farms, random forest algorithms were able to replicate the complex herd level diagnoses made by specialist veterinary clinicians with a high degree of accuracy.

Quantitative analysis of calf mortality in Great Britain.

National bodies in Great Britain (GB) have expressed concern over young stock health and welfare and identified calf survival as a priority; however, no national data have been available to quantify mortality rates. The aim of this study was to quantify the temporal incidence rate, distributional features, and factors affecting variation in mortality rates in calves in GB since 2011. The purpose was to provide information to national stakeholder groups to inform resource allocation both for knowledge exchange and future research.

Quantitative analysis of antimicrobial use on British dairy farms.

Antimicrobial resistance has been reported to represent a growing threat to both human and animal health, and concerns have been raised around levels of antimicrobial usage (AMU) within the livestock industry. To provide a benchmark for dairy cattle AMU and identify factors associated with high AMU, data from a convenience sample of 358 dairy farms were analysed using both mass-based and dose-based metrics following standard methodologies proposed by the European Surveillance of Veterinary Antimicrobial Consumption project. Metrics calculated were mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses (DDDvet) and defined course doses (DCDvet).

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

Background: Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011.

Sponsorship bias and quality of randomised controlled trials in veterinary medicine.

Background: Randomised controlled trials (RCTs) are considered the gold standard form of evidence for assessing treatment efficacy, but many factors can influence their reliability including methodological quality, reporting quality and funding source. The aim of this study was to examine the relationship between funding source and positive outcome reporting in veterinary RCTs published in 2011 and to assess the risk of bias in the RCTs identified.

Methods: A structured search of PubMed was used to identify feline, canine, equine, bovine and ovine clinical trials examining the efficacy of pharmaceutical interventions published in 2011.

The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse.

This study investigated the influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9 horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and the limbs were perfused with 500 mg genta-micin diluted to the assigned volume via a catheter placed in the lateral palmar digital vein at the level of the proximal sesamoid bones.

Identification, extraction and quantification of the synthetic cannabinoid JWH-018 from commercially available herbal marijuana alternatives.

In this work, methods for the rapid identification, extraction, and quantification of the synthetic cannabinoid, JWH-018, from commercially available "Spice" (a herbal marijuana alternative) are presented. JWH-018 was identified in three different products using time-of-flight (TOF) mass spectrometry coupled with a direct analysis in real time (DART) ionization source, a process that was completed in less then five minutes and required no sample preparation. Extraction of the JWH-018 from the spice samples using an automated accelerated solvent extraction (ASE) instrument provided clean extracts with few plant pigments.

Identification of a periorbital wooden foreign body as the cause of chronic ocular discharge in a horse.

The clinical, diagnostic and therapeutic features of a horse with a wooden foreign body embedded in the deep portion of the right masseter muscle adjacent to the right orbit are presented. The purpose of this report is to describe the clinical presentation, magnetic resonance imaging findings and treatment of a penetrating wooden foreign body in a horse that had no history of trauma or evidence of a puncture wound. This report documents the usefulness of magnetic resonance imaging to detect a wooden foreign body embedded in the soft tissues of a horse with a chronic copious ocular discharge.

Confocal microscopy studies of a model oligoribonucleotide HIV inhibitor.

Previous work has shown that novel amphipalhic oligo and polyribonucleotides are potent inhibitors of HIV. It was hypothesized that the mechanism(s) of action for these compounds might be inhibition of retroviral reverse transcriptase (RT) and/or viral uptake by cells. A fluorescent oligonucleotide analog was prepared, and confocal microscopy studies were undertaken in order to examine oligonucleotide-cell interactions.

Oligonucleotides and polyribonucleotides: a review of antiviral activity.

Current antiviral therapies are insufficient for treating emerging, re-emerging and established viral diseases. In an effort to find new therapeutics, oligo- and polyribonucleotides are being studied for their antiviral capabilities. Studies have shown that uniquely modified single- and double-stranded nucleic acid constructs are effective in inhibiting viral proliferation by various mechanisms.

Antiviral amphipathic oligo- and polyribonucleotides: analogue development and biological studies.

A series of novel N1 alkylated purine nucleic acids were polymerized either enzymatically or by automated synthesis to further establish the SAR requirements for HIV, RT, and HCMV activity. Out of the series, two constructs, 2'-O-methyl-1-allylinosinic acid phosphorothioate 33-mer (16) and an oligomer incorporating 1-propyl-6-thioinosinic acid residues (20), were found to be highly active under all three assay conditions. SAR studies indicate that sulfur incorporation, high molecular weight, and low steric bulk at N1 all can be important for activity.

"Senseless" antiviral polyribonucleotides: poly (1-propargylinosinic acid).

Previous work has shown that novel amphipathic oligo and polyribonucleotides exhibiting secondary structure in solution are potent inhibitors of HIV and HCMV replication and cytopathicity in tissue culture. It was hypothesized that the mechanism(s) of action for these compounds might be inhibition of retroviral reverse transcriptase (RT) and/or viral uptake by cells. Pursuit of the essential pharmacophore has led to the discovery of poly (1-propargylinosinic acid) (10), an HIV and HCMV-active polyribonucleotide lacking the secondary structure previously thought to be essential for the observed antiviral activity.

Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties.

The design and synthesis of a series of novel 5-substituted tryptamines with pharmacological activity at 5-HT1D and other monoamine receptors is described. Structural modifications of N- and C-linked (principally hydantoin) analogues at the 5-position were synthesized and their pharmacological activities were utilized to deduce significant steric and electrostatic requirements of the 5-HT1D and 5-HT2A receptor subtypes. Conformations of the active molecules were computed which, when overlaid, suggested a pharmacophore hypothesis which was consistent with the affinity and selectivity measured at 5-HT1D and 5-HT2A receptors.

Development of a novel series of trialkoxyaryl derivatives as specific and competitive antagonists of platelet activating factor.

The synthesis and structure-activity relationship (SAR) analysis of a novel series of trialkoxyaryl derivatives, as specific and competitive inhibitors of platelet activating factor (PAF), are described. Molecular modeling comparisons of PAF with the known antagonists Ginkgolide B and L-652731 led to the selection of N-[2-[(3,4,5-trimethoxybenzoyl)oxy]ethyl]-N,N,N-trimethylammonium iodide (1) from the Wellcome registry of compounds and to the synthesis of the lead compound N-[2-[[4-(hexyloxy)-3,5-dimethoxybenzoyl]oxy]ethyl]-N,N,N- trimethylammonium iodide (3, pKb 5.43).

A quantitative structure-activity relationship approach to the minimization of albumin binding.

The binding of 2,6-disubstituted xanthones to human serum albumin (HSA) has been investigated using an ultrafiltration technique. A set of 26 compounds was chosen for study using a selection procedure aimed at minimizing the interparameter correlations, while ensuring that the physicochemical properties covered the maximum possible range of values. The magnitude of binding has been expressed as the compound concentration required to produce a specified bound concentration, in preference to equilibrium constants and number of albumin binding sites.

Perspectives in QSAR: computer chemistry and pattern recognition.

Computer chemistry allows a detailed description of properties for a wide range of molecular environments. In these respects it offers substantial benefits to the QSAR (Quantitative Structure Activity Relationship) analyst. Problems associated with the resulting wide data matrices are, it is proposed, amenable to solution through multivariate 'pattern recognition' techniques.

Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood.

Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy-6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes.

A group of trimethoprim (TMP) analogues containing 3,5-dialkyl(or halo)-4-alkoxy, -hydroxy, or -amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably similar for rat, Neisseria gonorrhoeae, and Plasmodium berghei enzymes in all three series, although somewhat different for Escherichia coli DHFR, leading to the conclusion that the hydrophobic pockets are similar for the first three isozymes.