Opportunities for refinement in neuroscience: Indicators of wellness and post-operative pain in laboratory macaques

Being able to assess pain in nonhuman primates undergoing biomedical procedures is important for preventing and alleviating pain, and for developing better guidelines to minimise the impacts of research on welfare in line with the 3Rs principle of Refinement. Nonhuman primates are routinely used biomedical models however it remains challenging to recognise negative states, including pain, in these animals. This study aimed to identify behavioural and facial changes that could be used as pain or general wellness indicators in the rhesus macaque (Macaca mulatta). Thirty-six macaques scheduled for planned neuroscience procedures were opportunistically monitored at four times: Pre-Operative (PreOp), Post-Operative (PostOp) once the effects of anaesthesia had dissipated, Pre-Analgesia (PreAn) on the subsequent morning prior to repeating routine analgesic treatment, and Post-Analgesia (PostAn) following administration of analgesia. Pain states were expected to be absent in PreOp, moderate in PreAn, and mild or absent in PostOp and PostAn when analgesia had been administered. Three potential pain indicators were identified: lip tightening and chewing, which were most likely to occur in PreAn, and running which was least likely in PreAn. Arboreal behaviour indicated general wellness, while half-closed eyes, leaning of the head or body shaking indicated the opposite. Despite considerable individual variation, behaviour and facial expressions could offer important indicators of pain and wellness and should be routinely quantified, and appropriate interventions applied to prevent or alleviate pain, and promote positive welfare

Probing empirical contact networks by simulation of spreading dynamics

Disease, opinions, ideas, gossip, etc. all spread on social networks. How these networks are connected (the network structure) influences the dynamics of the spreading processes. By investigating these relationships one gains understanding both of the spreading itself and the structure and function of the contact network. In this chapter, we will summarize the recent literature using simulation of spreading processes on top of empirical contact data. We will mostly focus on disease simulations on temporal proximity networks -- networks recording who is close to whom, at what time -- but also cover other types of networks and spreading processes. We analyze 29 empirical networks to illustrate the methods

Suboptimal herd performance amplifies the spread of infectious disease in the cattle industry

Farms that purchase replacement breeding cattle are at increased risk of introducing many economically important diseases. The objectives of this analysis were to determine whether the total number of replacement breeding cattle purchased by individual farms could be reduced by improving herd performance and to quantify the effects of such reductions on the industry-level transmission dynamics of infectious cattle diseases. Detailed information on the performance and contact patterns of British cattle herds was extracted from the national cattle movement database as a case example. Approximately 69% of beef herds and 59% of dairy herds with an average of at least 20 recorded calvings per year purchased at least one replacement breeding animal. Results from zero-inflated negative binomial regression models revealed that herds with high average ages at first calving, prolonged calving intervals, abnormally high or low culling rates, and high calf mortality rates were generally more likely to be open herds and to purchase greater numbers of replacement breeding cattle. If all herds achieved the same level of performance as the top 20% of herds, the total number of replacement beef and dairy cattle purchased could be reduced by an estimated 34% and 51%, respectively. Although these purchases accounted for only 13% of between-herd contacts in the industry trade network, they were found to have a disproportionately strong influence on disease transmission dynamics. These findings suggest that targeting extension services at herds with suboptimal performance may be an effective strategy for controlling endemic cattle diseases while simultaneously improving industry productivity

Not all cows are epidemiologically equal:quantifying the risks of bovine viral diarrhoea virus (BVDV) transmission through cattle movements

International audienceMany economically important cattle diseases spread between herds through livestock movements. Traditionally, most transmission models have assumed that all purchased cattle carry the same risk of generating outbreaks in the destination herd. Using data on bovine viral diarrhoea virus (BVDV) in Scotland as a case example, this study provides empirical and theoretical evidence that the risk of disease transmission varies substantially based on the animal and herd demographic characteristics at the time of purchase. Multivariable logistic regression analysis revealed that purchasing pregnant heifers and open cows sold with a calf at foot were associated with an increased risk of beef herds being seropositive for BVDV. Based on the results from a dynamic within-herd simulation model, these findings may be partly explained by the age-related probability of animals being persistently infected with BVDV as well as the herd demographic structure at the time of animal introductions. There was also evidence that an epidemiologically important network statistic, "betweenness centrality" (a measure frequently associated with the potential for herds to acquire and transmit disease), was significantly higher for herds that supplied these particular types of replacement beef cattle. The trends for dairy herds were not as clear, although there was some evidence that open heifers and open lactating cows were associated with an increased risk of BVDV. Overall, these findings have important implications for developing simulation models that more accurately reflect the industry-level transmission dynamics of infectious cattle diseases

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Bayesian analysis of herd-level risk factors for bovine digital dermatitis in New Zealand dairy herds

Abstract Background Bovine digital dermatitis (BDD) is considered the most important infectious cause of lameness in dairy cattle worldwide, but has only recently been observed in New Zealand. Although many studies have investigated the risk factors for BDD in confined dairy systems, information on risk factors in pasture-based system is limited. Therefore a cross-sectional study including 59,849 animals from 127 dairy herds in four regions of New Zealand was conducted to identify the herd-level factors associated with the probability of a herd being BDD-lesion positive and with within-herd BDD prevalence. Results Purchasing heifers was associated with increased odds of a herd being BDD-lesion positive (odds ratio [OR]: 2.33, 95% probability interval [PI]: 1.26–4.42) and a cow being BDD affected (OR: 3.76, 95%PI: 1.73–8.38), respectively. Higher odds of a herd being BDD-lesion positive (OR: 2.06, 95%PI: 1.17–3.62) and a cow being BDD affected (OR: 2.87, 95%PI: 1.43–5.94) were also seen in herds where heifers co-grazed with cattle from other properties. In addition, using outside staff to treat lameness was associated with higher odds of a cow being BDD affected (OR: 2.18, 95%PI: 0.96–4.98). Conclusion This study highlighted that movements of heifers are significantly associated with the spread of BDD within and between dairy herds in New Zealand. To minimise the risk of disease introductions in herds where moving heifers cannot be avoided, it is best to purchase heifers only from herds where BDD-freedom has been confirmed and, if heifers have to graze-off a farm, they should be reared as a single biosecure management group, especially since animals may be BDD-infected without having clinically obvious lesions

A Profile of physiotherapy clinical education

The purpose of the study was to examine clinical education placement data to generate a profile of providers and examine the students? exposure to health care and educational factors during clinical education. A retrospective audit of clinical placement rosters was undertaken for 3 calendar years (2001?2003). Data were analysed overall and by clinical school for sites and placements, public or private sector and type of placement. Over the 3- year period, 209 sites provided 3475 clinical placements, with the number of placements increasing from 1066 placements in 2001 to 1133 in 2002 and to 1276 in 2003. Overall, 72.2% of placements were located in metropolitan Sydney. The proportion from regional providers increased over the 3 years from 11.8% to 15.1%. Overall 85.8% of placements were delivered by public providers. The profile indicated that a considerable number of clinical sites were utilised with an emphasis on large public hospitals. The challenge for curriculum development is to reduce the clinical education demands on current providers while ensuring graduates meet entry-level standards of physiotherapy.9 page(s

The Genetic Relatedness and Antimicrobial Resistance Patterns of Mastitis-Causing <i>Staphylococcus aureus</i> Strains Isolated from New Zealand Dairy Cattle

Staphylococcus aureus is one of the leading causes of bovine mastitis worldwide and is a common indication for use of antimicrobials on dairy farms. This study aims to investigate the association between on-farm antimicrobial usage and the antimicrobial resistance (AMR) profiles of mastitis-causing S. aureus. Whole-genome sequencing was performed on 57 S. aureus isolates derived from cows with either clinical or subclinical mastitis from 17 dairy herds in New Zealand. The genetic relatedness between isolates was examined using the core single nucleotide polymorphism alignment whilst AMR and virulence genes were identified in-silico. The association between gene presence-absence and sequence type (ST), antimicrobial susceptibility and dry cow therapy treatment was investigated using Scoary. Altogether, eight STs were identified with 61.4% (35/57) belonging to ST-1. Furthermore, 14 AMR-associated genes and 76 virulence-associated genes were identified, with little genetic diversity between isolates belonging to the same ST. Several genes including merR1 which is thought to play a role in ciprofloxacin-resistance were found to be significantly overrepresented in isolates sampled from herds using ampicillin/cloxacillin dry cow therapy. Overall, the presence of resistance genes remains low and current antimicrobial usage patterns do not appear to be driving AMR in S. aureus associated with bovine mastitis

The Genetic Relatedness and Antimicrobial Resistance Patterns of Mastitis-Causing Staphylococcus aureus Strains Isolated from New Zealand Dairy Cattle

Staphylococcus aureus is one of the leading causes of bovine mastitis worldwide and is a common indication for use of antimicrobials on dairy farms. This study aims to investigate the association between on-farm antimicrobial usage and the antimicrobial resistance (AMR) profiles of mastitis-causing S. aureus. Whole-genome sequencing was performed on 57 S. aureus isolates derived from cows with either clinical or subclinical mastitis from 17 dairy herds in New Zealand. The genetic relatedness between isolates was examined using the core single nucleotide polymorphism alignment whilst AMR and virulence genes were identified in-silico. The association between gene presence-absence and sequence type (ST), antimicrobial susceptibility and dry cow therapy treatment was investigated using Scoary. Altogether, eight STs were identified with 61.4% (35/57) belonging to ST-1. Furthermore, 14 AMR-associated genes and 76 virulence-associated genes were identified, with little genetic diversity between isolates belonging to the same ST. Several genes including merR1 which is thought to play a role in ciprofloxacin-resistance were found to be significantly overrepresented in isolates sampled from herds using ampicillin/cloxacillin dry cow therapy. Overall, the presence of resistance genes remains low and current antimicrobial usage patterns do not appear to be driving AMR in S. aureus associated with bovine mastitis