Protocol: Non-antibiotic, alternative approaches to the nursery phase of swine production: a scoping review

It is widely accepted that antibiotic use drives the development of antibiotic resistance. Hence it is important that swine production uses antibiotics in a judicious manner. In addition, the label claim for livestock antibiotic growth promoters (AGP) of importance to humans has been removed in Canada. In reality, antibiotics have contributed greatly to efficiencies in meat production and animal health. A reduction in the use of growth promoting antibiotics has ramifications for costs of meat production and animal welfare given that sick animals need to be treated, often with antibiotics. Consequences of similar AGP bans in swine production in Europe included an immediate increase in therapeutic use of antibiotics considered important for humans, particularly for nursery stage pigs in Denmark and the Netherlands. It is important to identify and advance our knowledge through the existing research of alternative approaches to antibiotic use, in the nursery stage of pig production. Scoping reviews are a relatively novel approach for synthesizing research evidence in the veterinary and livestock production research literature (Pham MT., 2014). They are useful for mapping the extent, range, and nature of existing literature on a broad topic area. In addition, scoping reviews are useful for identifying gaps in the literature and for determining the feasibility of conducting one or more systematic reviews to help answer a specific question about the effectiveness of a specific intervention in a specific population measuring a specific outcome (Arksey and O’Malley, 2005)

Equine Rhinitis A Virus Infection at a Standardbred Training Facility: Incidence, Clinical Signs, and Risk Factors for Clinical Disease

Respiratory disease is a common morbidity of young racehorses. Infections can lead to compromised welfare, and economic loss. Identification of risk factors for infection through clinical signs monitoring and collection of demographic, serologic, and contact network data can aid in the development of prevention and control strategies. The study objectives were to: (1) describe the transmission and clinical course of infectious respiratory disease in standardbred racehorses in a multi-barn training facility and, (2) identify demographic, serological, and contact network risk factors associated with Equine Rhinitis A virus (ERAV) respiratory disease. The study population included standardbred racehorses (age 1–5 years: n = 96) housed at a multi-barn training facility in southern Ontario. Clinical signs were monitored daily over a 41-day period in fall 2017. Descriptive statistics, including incidence rate, prevalence and incidence risk were calculated for the observed period. Associations between demographic, serologic, and contact pattern variables, and clinical disease status were investigated using multivariable logistic regression. Respiratory disease cases were characterized by mucopurulent discharge (100%), intermittent cough (37.7%), and ocular discharge (62.3%). Fever (>38.5°C) and inappetence were rarely reported (15.2 and 3.8%). Seroconversion to ERAV among cases was 75%. Total, and yearling-specific incidence risks were 52.5 and 87.9%. The cumulative incidence was 0.027 new cases/horse day. A negative association (OR = 0.011) between increasing age and respiratory disease was significant (p = < 0.001) in the final regression model. Yearling horses were at increased risk of infectious respiratory disease as demonstrated by the high yearling-specific incidence risk, and the negative association between age and infection. Disease control strategies, such as vaccination programs and isolation of new horses arriving from auction, should be targeted at young animals entering training facilities

Factors Associated With Time to Elimination of Porcine Epidemic Diarrhea Virus in Individual Ontario Swine Herds Based on Surveillance Data

Porcine epidemic diarrhea virus (PEDV) emerged into Canada in January of 2014. The virus was considered to be of high importance and the number of new cases were tracked using different mechanisms by stakeholders such as veterinary services from the provincial government and the swine industry. In addition to the initial date of infection, veterinary organizations in the swine industry maintained a disease control program (DCP) database that contained the date of declaration of freedom from PEDV in individual herds. Such data allowed for the determination of the duration of PEDV infection in individual herds based on herd type, year and season of diagnosis. Therefore, the objective of this study was to determine time to PEDV elimination in Ontario swine herds infected between 2014 and 2017, on the basis of records from the DCP database; and to identify factors associated with the likelihood of elimination. Duration of time to eliminate PEDV was estimated using Kaplan-Meier survival curves. The final Cox's proportional hazard model included herd type, season and year of diagnosis. The hazard of PEDV elimination for premises that were farrow-to-wean was 3.36 times larger (P-value: 0.044, 95% CI: 1.03, 10.93) than for farrow-to-feeder herds. Herds diagnosed in the summer and fall had hazard ratios of 1.40 (P-value: 0.044, 95% CI: 1.03, 10.93) and 7.32 (P-value: <0.001, 95% CI: 3.12, 17.18), respectively compared to herds diagnosed in the winter months. The hazard ratio for herds diagnosed in 2015 was 0.54 (P-value: 0.015, 95% CI: 0.33, 0.89) compared to herds diagnosed in 2014. Factors associated with time to elimination are likely reflective of the complexity of infection control practices applied in herds with different demographics and population structures, seasonal variability in the pathogen transmissibility, and the availability of resources to manage an emerging production-limiting disease. The median times to elimination were relatively long, which could be due to how it was measured, decisions made at the level of individual herds or delays related to reporting PEDV elimination. Design of control measures for production-limiting diseases at the regional level should take these factors into consideration

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Physics potential of a long-baseline neutrino oscillation experiment using a J-PARC neutrino beam and Hyper-Kamiokande

39 pages, 26 figures, submitted to PTE

Hyper-Kamiokande Design Report

325 pages325 pagesOn the strength of a double Nobel prize winning experiment (Super)Kamiokande and an extremely successful long baseline neutrino programme, the third generation Water Cherenkov detector, Hyper-Kamiokande, is being developed by an international collaboration as a leading worldwide experiment based in Japan. The Hyper-Kamiokande detector will be hosted in the Tochibora mine, about 295 km away from the J-PARC proton accelerator research complex in Tokai, Japan. The currently existing accelerator will be steadily upgraded to reach a MW beam by the start of the experiment. A suite of near detectors will be vital to constrain the beam for neutrino oscillation measurements. A new cavern will be excavated at the Tochibora mine to host the detector. The experiment will be the largest underground water Cherenkov detector in the world and will be instrumented with new technology photosensors, faster and with higher quantum efficiency than the ones in Super-Kamiokande. The science that will be developed will be able to shape the future theoretical framework and generations of experiments. Hyper-Kamiokande will be able to measure with the highest precision the leptonic CP violation that could explain the baryon asymmetry in the Universe. The experiment also has a demonstrated excellent capability to search for proton decay, providing a significant improvement in discovery sensitivity over current searches for the proton lifetime. The atmospheric neutrinos will allow to determine the neutrino mass ordering and, together with the beam, able to precisely test the three-flavour neutrino oscillation paradigm and search for new phenomena. A strong astrophysical programme will be carried out at the experiment that will detect supernova neutrinos and will measure precisely solar neutrino oscillation

Physics Potentials with the Second Hyper-Kamiokande Detector in Korea

We have conducted sensitivity studies on an alternative configuration of the Hyper-Kamiokande experiment by locating the 2nd Hyper-Kamiokande detector in Korea at $\sim$1100$-\$1300 km baseline. Having two detectors at different baselines improves sensitivity to leptonic CP violation, neutrino mass ordering as well as nonstandard neutrino interactions. There are several candidate sites in Korea with greater than 1 km high mountains ranged at an 1$-$3 degree off-axis angle. Thanks to larger overburden of the candidate sites in Korea, low energy physics, such as solar and supernova neutrino physics as well as dark matter search, is expected to be improved. In this paper sensitivity studies on the CP violation phase and neutrino mass ordering are performed using current T2K systematic uncertainties in most cases. We plan to improve our sensitivity studies in the near future with better estimation of our systematic uncertainties

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Physics potentials with the second Hyper-Kamiokande detector in Korea

Hyper-Kamiokande consists of two identical water-Cherenkov detectors of total 520 kt, with the first one in Japan at 295 km from the J-PARC neutrino beam with 2.5 degrees off-axis angles (OAAs), and the second one possibly in Korea at a later stage. Having the second detector in Korea would benefit almost all areas of neutrino oscillation physics, mainly due to longer baselines. There are several candidate sites in Korea with baselines of 1000-1300 km and OAAs of 1 degrees-3 degrees. We conducted sensitivity studies on neutrino oscillation physics for a second detector, either in Japan (JD x 2) or Korea (JD + KD), and compared the results with a single detector in Japan. Leptonic charge-parity (CP) symmetry violation sensitivity is improved, especially when the CP is non-maximally violated. The larger matter effect at Korean candidate sites significantly enhances sensitivities to non-standard interactions of neutrinos and mass ordering determination. Current studies indicate the best sensitivity is obtained at Mt. Bisul (1088 km baseline, 1.3 degrees OAA). Thanks to a larger (1000 m) overburden than the first detector site, clear improvements to sensitivities for solar and supernova relic neutrino searches are expected

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management