Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves.

Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves

Helpless priming sends CD8(+)T cells on the road to exhaustion

Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control. Recent work identifies a population of poorly differentiated TCF-1(+)PD-1(+)CD8(+)T cells as precursors of the terminally exhausted CTL pool. These "predysfunctional" CTLs are suggested to respond to PD-1 targeted therapy by giving rise to a pool of functional CTLs. Supported by gene expression analyses, we present a model in which lack of CD4(+)T cell help during CD8(+)T cell priming results in the formation of predysfunctional CTLs. Our model implies that predysfunctional CTLs are formed during priming and that the remedy for CTL dysfunction is to provide "help" signals for generation of optimal CTL effectors. We substantiate that this may be achieved by engaging CD4(+)T cells in new CD8(+)T cell priming, or by combined PD-1 blocking and CD27 agonism with available immunotherapeutic antibodies.Tumorimmunolog

Whole-Genome Sequencing and Concordance Between Antimicrobial Susceptibility Genotypes and Phenotypes of Bacterial Isolates Associated with Bovine Respiratory Disease.

Extended laboratory culture and antimicrobial susceptibility testing timelines hinder rapid species identification and susceptibility profiling of bacterial pathogens associated with bovine respiratory disease, the most prevalent cause of cattle mortality in the United States. Whole-genome sequencing offers a culture-independent alternative to current bacterial identification methods, but requires a library of bacterial reference genomes for comparison. To contribute new bacterial genome assemblies and evaluate genetic diversity and variation in antimicrobial resistance genotypes, whole-genome sequencing was performed on bovine respiratory disease-associated bacterial isolates (Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida) from dairy and beef cattle. One hundred genomically distinct assemblies were added to the NCBI database, doubling the available genomic sequences for these four species. Computer-based methods identified 11 predicted antimicrobial resistance genes in three species, with none being detected in M. bovis While computer-based analysis can identify antibiotic resistance genes within whole-genome sequences (genotype), it may not predict the actual antimicrobial resistance observed in a living organism (phenotype). Antimicrobial susceptibility testing on 64 H. somni, M. haemolytica, and P. multocida isolates had an overall concordance rate between genotype and phenotypic resistance to the associated class of antimicrobials of 72.7% (P < 0.001), showing substantial discordance. Concordance rates varied greatly among different antimicrobial, antibiotic resistance gene, and bacterial species combinations. This suggests that antimicrobial susceptibility phenotypes are needed to complement genomically predicted antibiotic resistance gene genotypes to better understand how the presence of antibiotic resistance genes within a given bacterial species could potentially impact optimal bovine respiratory disease treatment and morbidity/mortality outcomes

We’ve Been Down this Road Before: Evidence on the Health Consequences of Precarious Employment in Industrial Societies, 1840-1920

A large body of international scientific research now indicates that the growth of job insecurity, flexible/temporary work and precarious forms of self-employment have had significant negative consequences for occupational health and safety. What is often overlooked in debates over the ‘changing world of work’ is that today’s widespread use insecure and short term work is not new but represents a return to something more resembling labour markets in Australia, Europe and North America in the 19th and early 20th century. As this paper will seek to show, not only were precarious and exploitive working arrangements common during this period but the adverse effects of these on the health, safety and wellbeing was well documented in government inquiries, medical research, press reports and a variety of other sources. Drawing primarily on Australian and British sources, attention here will focus on casual labourers, sweated garment workers, the self-employed and merchant seamen. The paper highlights the valuable role historical research can play in shedding light on contemporary problems and policy debates.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business

Exploring efficient seamless handover in VANET systems using network dwell time

Vehicular ad hoc networks are a long-term solution contributing significantly towards intelligent transport systems (ITS) in providing access to critical life-safety applications and services. Although vehicular ad hoc networks are attracting greater commercial interest, current research has not adequately captured the real-world constraints in vehicular ad hoc network handover techniques. Therefore, in order to have the best practice for vehicular ad hoc network services, it is necessary to have seamless connectivity for optimal coverage and ideal channel utilisation. Due to the high velocity of vehicles and smaller coverage distances, there are serious challenges in providing seamless handover from one roadside unit (RSU) to another. Though other research efforts have looked at many issues in vehicular ad hoc networks (VANETs), very few research work have looked at handover issues. Most literature assume that handover does not take a significant time and does not affect the overall VANET operation. In our previous work, we started to investigate these issues. This journal provides a more comprehensive analysis involving the beacon frequency, the size of beacon and the velocity of the vehicle. We used some of the concepts of Y-Comm architecture such as network dwell time (NDT), time before handover (TBH) and exit time (ET) to provide a framework to investigate handover issues. Further simulation studies were used to investigate the relation between beaconing, velocity and the network dwell time. Our results show that there is a need to understand the cumulative effect of beaconing in addition to the probability of successful reception as well as how these probability distributions are affected by the velocity of the vehicle. This provides more insight into how to support life critical applications using proactive handover techniques

Implementation of a parentage control system in Portuguese beef-cattle with a panel of microsatellite markers

A study was conducted to assess the feasibility of applying a panel of 10 microsatellite markers in parentage control of beef cattle in Portugal. In the first stage, DNA samples were collected from 475 randomly selected animals of the Charolais, Limousin and Preta breeds. Across breeds and genetic markers, means for average number of alleles, effective number of alleles, expected heterozygosity and polymorphic information content, were 8.20, 4.43, 0.733 and 0.70, respectively. Enlightenment from the various markers differed among breeds, but the set of 10 markers resulted in a combined probability above 0.9995 in the ability to exclude a random putative parent. The marker-set thus developed was later used for parentage control in a group of 140 calves from several breeds, where there was the suspicion of possible faulty parentage recording. Overall, 76.4% of the calves in this group were compatible with the recorded parents, with most incompatibilities due to misidentification of the dam. Efforts must be made to improve the quality of pedigree information, with particular emphasis on information recorded at the calf's birth

Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

From Wiley via Jisc Publications RouterHistory: received 2020-09-04, rev-recd 2020-12-05, accepted 2020-12-29, pub-electronic 2021-03-06, pub-print 2021-05Article version: VoRPublication status: PublishedFunder: Ministry of Health, Welfare and Sports, The NetherlandsAbstract: Background: Patient‐relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia. Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables. Persons with hemophilia and multidisciplinary health care providers were involved in an iterative nominal consensus process to select the most important health outcomes and risk adjustment variables for persons with hemophilia. Recommendations were made for outcome measurement instruments. Results: Persons with hemophilia were defined as all men and women with an X‐linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII or IX with plasma activity levels <40 IU/dL. We recommend collecting the following 10 health outcomes at least annually, if applicable: (i) cure, (ii) impact of disease on life expectancy, (iii) ability to engage in normal daily activities, (iv) severe bleeding episodes, (v) number of days lost from school or work, (vi) chronic pain, (vii) disease and treatment complications, (viii) sustainability of physical functioning, (ix) social functioning, and (x) mental health. Validated clinical as well as patient‐reported outcome measurement instruments were endorsed. Demographic factors, baseline clinical factors, and treatment factors were identified as risk‐adjustment variables. Conclusion: A consensus‐based international set of health outcomes relevant to all persons with hemophilia, and corresponding measurement instruments, was identified for use in clinical care to facilitate harmonized longitudinal monitoring and comparison of outcomes