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Abstract Background There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S. population. The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19. Methods This was a cohort study using data from Optum’s longitudinal COVID-19 electronic health record database derived from a network of healthcare provider organizations across the US. The study included patients with confirmed COVID-19 (presence of ICD-10-CM code U07.1 and/or positive SARS-CoV-2 test) between January 2020 and November 2020. Patient characteristics and clinical variables at start of hospitalization were evaluated for their association with subsequent serious outcomes (critical care, mechanical ventilation, and death) using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, adjusted for demographic variables. Results Among 56,996 hospitalized COVID-19 patients (49.5% male and 72.4% ≥ 50 years), 11,967 received critical care, 9136 received mechanical ventilation, and 8526 died. The median duration of hospitalization was 6 days (IQR: 4, 11), and this was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Dyspnea and hypoxemia were the most prevalent symptoms and both were associated with serious outcomes in adjusted models. Additionally, temperature, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and oxygen saturation measured during hospitalization were predictors of serious outcomes as were several in-hospital diagnoses. The strongest associations were observed for acute respiratory failure (critical care: OR, 6.30; 95% CI, 5.99–6.63; ventilation: OR, 8.55; 95% CI, 8.02–9.11; death: OR, 3.36; 95% CI, 3.17–3.55) and sepsis (critical care: OR, 4.59; 95% CI, 4.39–4.81; ventilation: OR, 5.26; 95% CI, 5.00–5.53; death: OR, 4.14; 95% CI, 3.92–4.38). Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during hospitalization were inversely associated with death (OR, 0.57; 95% CI, 0.54–0.61). Conclusions We identified several clinical characteristics associated with receipt of critical care, mechanical ventilation, and death among COVID-19 patients. Future studies into the mechanisms that lead to severe COVID-19 disease are warranted.

Abstract Background Student feedback has played an important role in the maintenance of quality and standards in higher education. Perhaps the most commonly used method to capture feedback is a series of questions or statements where students indicate their degree of satisfaction or agreement. Focus groups offer an alternative means of capturing ‘richer’ qualitative data relating to students’ thoughts on course structure. Aside from student evaluations, student examination performance has been used as a method to evaluate the efficacy of curriculum changes at programme level. However, this data is utilised less so at a ‘finer detail’ level to identify specific issues with the delivery of teaching. Case presentation The purpose of this report was to outline the approach taken using qualitative and quantitative data to identify problems with a specific area of teaching, inform a new teaching approach and to assess the impact of those changes. Following quantitative and qualitative analysis, a practical class on dairy herd fertility performance was highlighted as an area for improvement. After the introduction of the newly formatted practical class with a greater focus on self-directed learning, there was a significant increase in the average score (p

Abstract In Autumn 2011, nonspecific clinical signs of pyrexia, diarrhoea, and drop in milk yield were observed in dairy cattle near the German town of Schmallenberg at the Dutch/German border. Targeted veterinary diagnostic investigations for classical endemic and emerging viruses could not identify a causal agent. Blood samples were collected from animals with clinical signs and subjected to metagenomic analysis; a novel orthobunyavirus was identified and named Schmallenberg virus (SBV). In late 2011/early 2012, an epidemic of abortions and congenital malformations in calves, lambs and goat kids, characterised by arthrogryposis and hydranencephaly were reported in continental Europe. Subsequently, SBV RNA was confirmed in both aborted and congenitally malformed foetuses and also in Culicoides species biting midges. It soon became evident that SBV was an arthropod-borne teratogenic virus affecting domestic ruminants. SBV rapidly achieved a pan-European distribution with most countries confirming SBV infection within a year or two of the initial emergence. The first Irish case of SBV was confirmed in the south of the country in late 2012 in a bovine foetus. Since SBV was first identified in 2011, a considerable body of scientific research has been conducted internationally describing this novel emerging virus. The aim of this systematic review is to provide a comprehensive synopsis of the most up-to-date scientific literature regarding the origin of SBV and the spread of the Schmallenberg epidemic, in addition to describing the species affected, clinical signs, pathogenesis, transmission, risk factors, impact, diagnostics, surveillance methods and control measures. This review also highlights current knowledge gaps in the scientific literature regarding SBV, most notably the requirement for further research to determine if, and to what extent, SBV circulation occurred in Europe and internationally during 2017 and 2018. Moreover, recommendations are also made regarding future arbovirus surveillance in Europe, specifically the establishment of a European-wide sentinel herd surveillance program, which incorporates bovine serology and Culicoides entomology and virology studies, at national and international level to monitor for the emergence and re-emergence of arboviruses such as SBV, bluetongue virus and other novel Culicoides-borne arboviruses.

Abstract Background Quantitative genetic studies suggest the existence of variation at the genome level that affects the ability of cattle to resist to parasitic diseases. The objective of the current study was to identify regions of the bovine genome that are associated with resistance to endo-parasites. Methods Individual cattle records were available for Fasciola hepatica-damaged liver from 18 abattoirs. Deregressed estimated breeding values (EBV) for F. hepatica-damaged liver were generated for genotyped animals with a record for F. hepatica-damaged liver and for genotyped sires with a least one progeny record for F. hepatica-damaged liver; 3702 animals were available. In addition, individual cow records for antibody response to F. hepatica on 6388 genotyped dairy cows, antibody response to Ostertagia ostertagi on 8334 genotyped dairy cows and antibody response to Neospora caninum on 4597 genotyped dairy cows were adjusted for non-genetic effects. Genotypes were imputed to whole-sequence; after edits, 14,190,141 single nucleotide polymorphisms (SNPs) and 16,603,644 SNPs were available for cattle with deregressed EBV for F. hepatica-damaged liver and cows with an antibody response to a parasitic disease, respectively. Association analyses were undertaken using linear regression on one SNP at a time, in which a genomic relationship matrix accounted for the relationships between animals. Results Genomic regions for F. hepatica-damaged liver were located on Bos taurus autosomes (BTA) 1, 8, 11, 16, 17 and 18; each region included at least one SNP with a p value lower than 10−6. Five SNPs were identified as significant (q value

Objectives: To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya. Materials and methods: Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls. Results: Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life. Conclusion: In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures. Keywords: Bypass, Perfusion, Stenosis

Antiseizure medications (ASM) may contribute to adverse fetal outcomes in pregnant women with epilepsy (WWE). Folate processing (Methylenetetrahydrofolate reductase, MTHFR) gene abnormalities are common in women with epilepsy and depression. L-methylfolate supplements may bypass MTHFR deficiencies, yet their use in WWE during gestation or on fetal development is not well studied. We examine pregnancy histories of three WWE who supplemented with either folate or L-methylfolate and methylcobalamin (methylated B12) during pregnancies. Their pregnancy outcomes improved with L-methylfolate and methylcobalamin supplementation. L-methylfolate and methylcobalamin supplementation merits further study in WWE who have MTHFR mutations, fertility, recurrent miscarriage and or depression histories.

Abstract Background Following the emergence of Schmallenberg virus (SBV) in Ireland in 2012, a sentinel herd surveillance program was established in the south of Ireland with the primary aim of investigating the species composition and abundance of Culicoides on livestock farms in the region. Methods Ultraviolet-light trapping for Culicoides was carried out on 10 sentinel farms. Each site was sampled fortnightly over 16 weeks (21st July to 5th November 2014). One Onderstepoort Veterinary Institute UV light trap was run overnight at each site and catches were transferred immediately into 70% ethanol. Culicoides were morphologically identified to species level. Collection site habitats were characterised using the Phase 1 habitat survey technique (Joint Nature Conservation Committee). Results A total of 23,929 individual Culicoides from 20 species was identified, including one species identified in Ireland for the first time, Culicoides cameroni. The most abundant species identified were Culicoides obsoletus/Culicoides scoticus (38%), Culicoides dewulfi (36%), Culicoides pulicaris (9%), Culicoides chiopterus (5%) and Culicoides punctatus (5%), comprising 93% of all Culicoides specimens identified. Collection site habitats were dominated by improved grassland and a combination of broadleaf woodland and native woodland species. Conclusions The most abundant species of Culicoides identified were the putative vectors of bluetongue virus (BTV) and SBV in northern Europe. Their presence and abundance demonstrates the potential for future transmission of arboviruses among livestock in this region.

As part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 – June 2013 (RV1 and cIPV) and January 2004 – July 2008 (hIPV). Outcomes were identified in the 0–59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0–7 day post-vaccination period to a 15–30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 – 3.38; hIPV: 2.05, 95% CI: 1.24 – 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 – 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Objectives: To investigate if glucose levels influence seizure patterns. Materials and methods: In a patient with RNS/NeuroPace implanted bi-temporally and type 1 diabetes mellitus, seizure event times and onset locations were matched to continuous tissue glucose. Results: Left focal seizure (LFS, n = 22) glucoses averaged 169 mg/dL, while right focal seizure (RFS, n = 23) glucoses averaged 131 mg/dL (p = 0.03). LFS occurred at mean time 17:02 while RFS occurred at 04:23. LFS spread to the contralateral side (n = 19) more than RFS (n = 2). Conclusion: Seizure onset laterality and spread vary with glucose and time of seizure. Keywords: Stimulation, Hypometabolism, Nonketotic, Glucose, Insulin, Circadian

Objectives: To match responsive neurostimulator (RNS) and polysomnographic data to determine if RNS detections and stimulations correlate with measurements of sleep disordered breathing and continuous glucose measurements (CGM). Materials and methods: In a patient with an RNS with detection/stimulation leads implanted bi-temporally detection-stimulation counts were matched by time with coinciding polysomnogram and CGM data. Results: Temporal dispersion of RNS DSC were independent of measures of sleep apnea, hypopnea or glucose. Conclusion: Hippocampal nighttime responsive neurostimulation therapies did not appear to worsen measures of normal or abnormal sleep. Keywords: Stimulation, Sleep, Central, Obstructive, Glucose, Insulin

Abstract Background Herd fertility in pasture-based dairy farms is a key driver of farm economics. Models for predicting nulliparous reproductive outcomes are rare, but age, genetics, weight, and BCS have been identified as factors influencing heifer conception. The aim of this study was to create a simulation model of heifer conception to service with thorough evaluation. Methods Artificial Insemination service records from two research herds and ten commercial herds were provided to build and evaluate the models. All were managed as spring-calving pasture-based systems. The factors studied were related to age, genetics, and time of service. The data were split into training and testing sets and bootstrapping was used to train the models. Logistic regression (with and without random effects) and generalised additive modelling were selected as the model-building techniques. Two types of evaluation were used to test the predictive ability of the models: discrimination and calibration. Discrimination, which includes sensitivity, specificity, accuracy and ROC analysis, measures a model’s ability to distinguish between positive and negative outcomes. Calibration measures the accuracy of the predicted probabilities with the Hosmer-Lemeshow goodness-of-fit, calibration plot and calibration error. Results After data cleaning and the removal of services with missing values, 1396 services remained to train the models and 597 were left for testing. Age, breed, genetic predicted transmitting ability for calving interval, month and year were significant in the multivariate models. The regression models also included an interaction between age and month. Year within herd was a random effect in the mixed regression model. Overall prediction accuracy was between 77.1% and 78.9%. All three models had very high sensitivity, but low specificity. The two regression models were very well-calibrated. The mean absolute calibration errors were all below 4%. Conclusion Because the models were not adept at identifying unsuccessful services, they are not suggested for use in predicting the outcome of individual heifer services. Instead, they are useful for the comparison of services with different covariate values or as sub-models in whole-farm simulations. The mixed regression model was identified as the best model for prediction, as the random effects can be ignored and the other variables can be easily obtained or simulated.

Abstract Veterinary clinicians and students commonly use diagnostic approaches appropriate for individual cases when conducting herd problem-solving. However, these approaches can be problematic, in part because they make limited use of epidemiological principles and methods, which has clear application during the investigation of herd problems. In this paper, we provide an overview of diagnostic approaches that are used when investigating individual animal cases, and the challenges faced when these approaches are directly translated from the individual to the herd. Further, we propose an investigative framework to facilitate epidemiological thinking during herd problem-solving. A number of different approaches are used when making a diagnosis on an individual animal, including pattern recognition, hypothetico-deductive reasoning, and the key abnormality method. Methods commonly applied to individuals are often adapted for herd problem-solving: ‘comparison with best practice’ being a herd-level adaptation of pattern recognition, and ‘differential diagnoses’ a herd-level adaptation of hypothetico-deductive reasoning. These approaches can be effective, however, challenges can arise. Herds are complex; a collection of individual cows, but also additional layers relating to environment, management, feeding etc. It is unrealistic to expect seamless translation of diagnostic approaches from the individual to the herd. Comparison with best practice is time-consuming and prioritisation of actions can be problematic, whereas differential diagnoses can lead to ‘pathogen hunting’, particularly in complex cases. Epidemiology is the science of understanding disease in populations. The focus is on the population, underpinned by principles and utilising methods that seek to allow us to generate solid conclusions from apparently uncontrolled situations. In this paper, we argue for the inclusion of epidemiological principles and methods as an additional tool for herd problem-solving, and outline an investigative framework, with examples, to effectively incorporate these principles and methods with other diagnostic approaches during herd problem-solving. Relevant measures of performance are identified, and measures of case frequencies are calculated and compared across time, in space and among animal groupings, to identify patterns, clues and plausible hypotheses, consistent with potential biological processes. With this knowledge, the subsequent investigation (relevant on-farm activities, diagnostic testing and other examinations) can be focused, and actions prioritised (specifically, those actions that are likely to make the greatest difference in addressing the problem if enacted). In our experience, this investigative framework is an effective teaching tool, facilitating epidemiological thinking among students during herd problem-solving. It is a generic and robust process, suited to many herd-based problems.

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed. Keywords: Marijuana, Sudden unexplained death in epilepsy, Cannabidiol, Tetrahydrocannabinol, Therapy

Objectives: The objective of this study was to review software errors known as single event upsets (SEUs) or bit flips due to cosmic rays in epilepsy neurostimulators. Materials and methods: A case report of a single event upset or bit flip is discussed; device manufacturers and publicly available data were queried for both incidence and types of error as well as strategies of software error mitigation. Results: Neurostimulators, like other implanted devices such as pacemakers, are prone to single event upsets. Strategies for SEU mitigation are reviewed. Conclusions: Cosmic radiation can threaten RAM and settings of neurostimulators; neuromodulation teams and device designers need to take this threat into account when designing multifunctional neuromodulation systems.

Herd-level risk factors related to the cow’s environment have been associated with lameness. Uncomfortable stall surface and inadequate depth of bedding as well as abrasive alley way surface are contributing factors to increased levels of lameness. Access to pasture has been found as having a beneficial effect on cows’ locomotion. However, dairy cattle managed under grazing conditions are exposed to a different set of risk factors for lameness, mainly associated with cow tracks. Cow-based risk factors for lameness are not as clearly defined as the herd level risk factors. The objective of the present study was to use routine herd health monitoring data to identify cow-based risk factors for lameness and utilise this information to indicate cows at risk of developing lameness in the first 150 days of lactation. Lameness data were gathered from 10 pasture-based dairy herds. A total of 1715 cows were monitored, of which 1675 cows were available for analysis. Associations between lameness status and potential cow-level risk factors were determined using multivariable logistic regression. Parity 3 and 4 + cows showed odd ratios (OR’s) for lameness of 3.92 and 8.60 respectively (95% confidence interval (CI) 2.46−6.24; 5.68−13.0). Maximum loss of Body condition score (BCS) after calving exhibits OR’s for lameness of 1.49 (95% CI 1.08−2.04) if cows lost 0.5 in BCS after calving and 2.26 (95% CI 1.30−3.95) for cows losing more than 0.5 BCS. Animals calving in BCS 3.25 and ≥ 3.5 had correlating OR’s of 0.54 (95% CI 0.34−0.87) and 0.33 (95% CI 0.16−0.65) for being lame compared to cows calving with BCS ≤ 2.75. Data gathered as part of herd health monitoring can be used in conjunction with lameness records to identify shortcomings in lameness management. Findings and recommendations on lameness management can be formulated from readily available information on cow-based risk factors for lameness.

The influence of plant traits on forest fire behaviour has evolutionary, ecological and management implications, but is poorly understood and frequently discounted. We use a process model to quantify that influence and provide validation in a diverse range of eucalypt forests burnt under varying conditions. Measured height of consumption was compared to heights predicted using a surface fuel fire behaviour model, then key aspects of our model were sequentially added to this with and without species-specific information. Our fully specified model had a mean absolute error 3.8 times smaller than the otherwise identical surface fuel model (p < 0.01), and correctly predicted the height of larger (≥1 m) flames 12 times more often (p < 0.001). We conclude that the primary endogenous drivers of fire severity are the species of plants present rather than the surface fuel load, and demonstrate the accuracy and versatility of the model for quantifying this.

A 19-year-old muscular male with a history of epilepsy presented following two convulsive events. Levetiracetam (LEV) was given as an additional therapy, resulting in a marked boost in creatine phosphokinase (CPK) that could not easily be explained by renal dysfunction or rhabdomyolysis alone. Levetiracetam discontinuation caused CPK levels to quickly normalize and should be considered in patients with persisting CPK elevations postconvulsive seizure.