Temporal trends in equine sperm progressive motility: a systematic review and meta-regression.

In brief: Adverse trends in reproductive function are a concern in humans, companion, livestock, and wildlife species. This study indicates that equine populations are at risk of a comparable decline in sperm progressive motility. Abstract: There is increasing evidence reporting geographically sensitive adverse trends in human semen quality, with parallel trends observed in the dog sentinel. Despite significant economic and welfare complications associated with poor testicular function, trends in current equine populations are undetermined. Given the predictive value of sperm progressive motility (PMOT) in male factor infertility and fertilisation potential, research determining trends in this parameter is warranted. This research analysed trends in stallion sperm PMOT through systematic review and meta-regression. Using a comprehensive search strategy, Scopus, Embase (Ovid), Medline (Ovid), and VetMed (CAB direct) were scoped for eligible data. Using best practices, 230 meta-data points from 229 articles published from 1991 to 2021 were collated for meta-regression analysis. Sperm PMOT declined significantly between 1984 and 2019 (simple linear regression: b -0.340, P = 0.017; meta-regression: b -0.610, P ≤ 0.001). Overall and yearly PMOT declines were predicted at 33.51 and 0.96%, respectively (1984: 63.69 ± 5.07%; 2019: 42.35 ± 3.69%). Trends remained consistent irrespective of sensitivity analyses. Yearly and overall declines were stronger in western (yearly: 0.75%, overall: 26.29%) compared to non-western (yearly: 0.46%, overall: 10.65%) populations. Adverse trends contribute vital data to the debate surrounding declining semen quality, supporting the use of equines as novel comparative models for human reproduction. Results could have significant economic, health, and welfare consequences for equine breeding sectors. A comparable decline in human, dog, and horse sperm quality is indicative of a common environmental aetiology, indicating the need for a holistic One Health approach in determining causes and developing preventative strategies.

Crosswalks between the Oxford hip and knee scores and the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To develop and validate bi-directional crosswalks between the Oxford Hip Score (OHS) and HOOS-12 summary impact score, and between the Oxford Knee Score (OKS) and KOOS-12 summary impact score. METHODS: Data were sourced from the Australian Orthopaedic Association National Joint Replacement Registry Patient-Reported Outcome Measures Program. Patients undergoing primary joint replacement for osteoarthritis who completed the OHS and HOOS-12 or OKS and KOOS-12 instruments were included in the analysis. An equipercentile method was used to create four crosswalks, with the distribution of scores smoothed using log-linear models prior to equating. Crosswalk validity was assessed through comparison of actual vs derived scores, Pearson correlation coefficients, root mean square errors (RMSE) and Bland-Altman plots. RESULTS: Paired OHS/HOOS-12 data and paired OKS/KOOS-12 data were available for 4,513 patients undergoing total hip replacement and 5,942 patients undergoing total knee replacement, respectively. Minimal differences were observed between actual and crosswalk-derived mean scores (actual OHS 27.55 vs derived OHS 27.56; actual HOOS-12 53.28 vs derived HOOS-12 53.31; actual OKS 27.34 vs derived OKS 27.34; actual KOOS-12 50.51 vs derived KOOS-12 50.58). High correlation was observed between actual and derived scores (Pearson's r for hip-specific instruments: 0.943-0.946; Pearson's r for knee-specific instruments: 0.925-0.931). Plotted actual vs mean derived scores also indicated robust concordance across the breadth of the instrument scales. CONCLUSION: These crosswalks provide close approximations of actual OHS, OKS, HOOS-12 and KOOS-12 scores, as indicated by multiple validation metrics. They offer a resource for clinicians, researchers and arthroplasty registries to support PROMs score conversion and data harmonisation efforts.

Observing the use of knee arthroplasty appropriateness tools in clinical practice: do appropriateness criteria tools predict surgeon decision-making?

OBJECTIVE: The primary aim of this study was to evaluate the agreement between surgeons and two validated total knee arthroplasty (TKA) appropriateness tools, and secondarily to compare Australian appropriateness rates to those reported internationally. METHODS: A consecutive sample of patients from one public hospital arthroplasty clinic and a convenience sample from private rooms of surgeons in New South Wales, Australia (n = 11), referred for surgical opinion regarding TKA were enrolled over 1 year. Surgeons applied appropriateness tools created by Escobar et al. and the American Academy of Orthopaedic Surgeons (AAOS). Correlation between the appropriateness tools and surgeon's decisions were evaluated. RESULTS: There were 368 patients enrolled, and contrasting rates of being "appropriate" for surgery were identified between the Escobar (n = 109, 29.6%) and AAOS (n = 292, 79.3%) tools. Surgeon agreement with the Escobar tool was substantial (ĸ = 0.61, 95%CI: 0.53-0.69) compared to slight with the AAOS tool (ĸ = 0.11, 95%CI: 0.06-0.16). Of those advised against TKA (n = 179, 48.6%), the AAOS tool suggested many patients (n = 111, 62.0%) were "appropriate" compared to the Escobar tool (n = 12, 6.7%). CONCLUSIONS: Surgeons rated patients seeking opinion for TKA as appropriate over half the time, however the AAOS tool had low correlation with surgeons as opposed to the Escobar tool. This was illustrated by both tools rating a majority of patients to be operated on as appropriate, but only the AAOS tool considering most patients not chosen for surgery to be appropriate. When comparing previously published appropriateness rates, appropriateness in Australia, USA, Spain and Qatar was found to be similar.

Performance of the HOOS-12 and KOOS-12 instruments for evaluating outcomes from joint replacement surgery.

OBJECTIVE: To evaluate the psychometric properties of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and Knee injury and Osteoarthritis Outcome Score (KOOS-12) for use in evaluating outcomes after joint replacement for osteoarthritis. DESIGN: Patient-reported outcomes data collected by the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. HOOS-12 and KOOS-12 domain (pain, function, quality of life) and summary impact data were available. The Oxford Hip Score (OHS), Oxford Knee Score (OKS) and EQ-5D-5L were used as comparators. Instruments were administered pre-operatively and at 6 months post-operatively. Internal consistency reliability, floor and ceiling effects, convergent validity, known groups validity, and responsiveness were evaluated using standard psychometric techniques. RESULTS: Baseline HOOS-12 and KOOS-12 data were available for 3,023 patients undergoing primary total hip replacement and 4,010 patients undergoing primary total knee replacement. At baseline, high internal consistency was demonstrated for all domains and summary scores (Cronbach's alpha: HOOS-12 = 0.81-0.93; KOOS-12 = 0.82-0.92). Post-operative ceiling effects (>15% of patients scoring the best possible score) were identified for the HOOS-12 pain (46%), function (39%) and quality of life domains (26%) and summary score (17%), and for the KOOS-12 pain (21%) and function domains (18%). The HOOS-12 and KOOS-12 could differentiate between two known groups (lowest/highest OHS or OKS quartiles post-operatively; p < 0.001) and were highly responsive to change (effect sizes for HOOS-12: 2.20-2.83; KOOS-12: 1.82-2.35). CONCLUSION: The HOOS-12 and KOOS-12 have good psychometric properties for capturing joint replacement outcomes including excellent responsiveness, although ceiling effects may limit monitoring of post-operative improvement.

Implications for research and clinical use from a Rasch analysis of the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To evaluate the structural validity of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and 12-item Knee injury and Osteoarthritis Outcome Score (KOOS-12) using Rasch analysis and consider psychometric implications for research and clinical use. METHOD: Individual-level HOOS-12 and KOOS-12 data from the Australian Orthopaedic Association National Joint Replacement Registry, collected before and after primary total hip and knee replacement, were used for this analysis. Using the Rasch analytic approach, overall model fit and item fit were examined, together with potential reasons for misfit including response threshold ordering, differential item functioning, internal consistency, unidimensionality and item targeting. RESULTS: Overall misfit to the Rasch model was evident for both instruments. A degree of item misfit was also observed, although most items demonstrated logical sequencing of response options. Only two items (hip/knee pain frequency and awareness of hip/knee problems) displayed disordered response thresholds. The pain, function, and quality of life domains of the HOOS-12 and KOOS-12 demonstrated excellent internal consistency reliability (person separation index: 0.80-0.93) and unidimensionality. A mismatch between item difficulty and person ability scores at the highest end of the HOOS-12 and KOOS-12 scales contributed to post-operative ceiling effects (mean logit for HOOS-12: 3.57; KOOS-12: 2.58; ≈0 indicates well-targeted scale). CONCLUSION: We found evidence to support the structural validity of the three HOOS-12 and KOOS-12 domains for evaluating joint replacement outcomes. However, there may be missing content in both instruments particularly for high-functioning patients. Minor refinement of some response options may be warranted to improve item performance.

Motor Conflict: Revealing Involuntary Conditioned Motor Preparation Using Transcranial Magnetic Stimulation.

Preparing actions to achieve goals, overriding habitual responses, and substituting actions that are no longer relevant are aspects of motor control often assumed to be driven by deliberate top-down processes. In the present study, we investigated whether motor control could come under involuntary control of environmental cues that have been associated with specific actions in the past. We used transcranial magnetic stimulation (TMS) to probe corticospinal excitability as an index of motor preparation, while participants performed a Go/No-Go task (i.e., an action outcome or no action outcome task) and rated what trial was expected to appear next (Go or No-Go). We found that corticospinal excitability during a warning cue for the upcoming trial closely matched recent experience (i.e., cue-outcome pairings), despite conflicting with what participants expected would appear. The results reveal that in an action-outcome task, neurophysiological indices of motor preparation show changes that are consistent with participants learning to associate a preparatory warning cue with a specific action, and are not consistent with the action that participants explicitly anticipate making. This dissociation with conscious expectancy ratings reveals that conditioned responding and motor preparation can operate independently of conscious expectancies about having to act.

Rates, costs, return to work and reoperation following spinal surgery in a workers' compensation cohort in New South Wales, 2010-2018: a cohort study using administrative data.

BACKGROUND: Internationally, elective spinal surgery rates in workers' compensation populations are high, as are reoperation rates, while return-to-work rates following spinal surgery are low. Little information is available from Australia. The aim of this study was to describe the rates, costs, return to work and reoperation following elective spinal surgery in the workers' compensation population in New South Wales (NSW), Australia. METHODS: This retrospective cohort study used administrative data from the State Insurance Regulatory Authority, the government organisation responsible for regulating and administering workers' compensation insurance in NSW. These data cover all workers' compensation-insured workers in New South Wales (over 3 million workers/year). We identified a cohort of insured workers who underwent elective spinal surgery (fusion or decompression) between January 1, 2010 and December 31, 2018. People who underwent surgery for spinal fracture or dislocation, or who had sustained a traumatic brain injury were excluded. The main outcome measures were annual spinal surgery rates, cost of the surgical episode, cumulative costs (surgical, hospital, medical and physical therapy) to 2 years post-surgery, and reoperation and return-to-work rates 2 years post-surgery. RESULTS: There were 9343 eligible claims (39.1 % fusion; 59.9 % decompression); claimants were predominantly male (75 %) with a mean age of 43 (range 18 to 75) years. Spinal surgery rates ranged from 15 to 29 surgeries per 100,000 workers per year, fell from 2011-12 to 2014-15 and rose thereafter. The average cost in Australian dollars for a surgical episode was $46,000 for a spinal fusion and $20,000 for a decompression. Two years post-fusion, only 19 % of people had returned to work at full capacity; 39 % after decompression. Nineteen percent of patients underwent additional spinal surgery within 2 years of the index surgery, to a maximum of 5 additional surgeries. CONCLUSION: Rates of workers' compensation-funded spinal surgery did not rise significantly during the study period, but reoperation rates are high and return-to-work rates are low in this population at 2 years post- surgery. In the context of the poor evidence base supporting lumbar fusion surgery, the high cost, increasing rates, and the increased likelihood of poor outcomes in the workers' compensation population, we question the value of this procedure in this setting.

An 11-year review of hip fracture hospitalisations, health outcomes, and predictors of access to in-hospital rehabilitation for adults ≥ 65 years living with and without dementia: a population-based cohort study.

This study examined hip fracture hospitalisation trends and predictors of access to rehabilitation for adults aged ≥ 65 years living with and without dementia. The hospitalisation rate was 2.5 times higher for adults living with dementia and adults who lived in aged care were between 4.8 and 9.3 times less likely to receive rehabilitation. INTRODUCTION: To examine hip fracture hospitalisation temporal trends, health outcomes, and predictors of access to in-hospital rehabilitation for older adults living with and without dementia. METHODS: A population-based retrospective cohort study of adults aged ≥ 65 years hospitalised with a hip fracture during 2007-2017 in New South Wales, Australia. RESULTS: Of the 69,370 hip fracture hospitalisations, 27.1% were adults living with dementia. The hip fracture hospitalisation rate was 2.5 times higher for adults living with dementia compared with adults with no dementia (1186.6 vs 492.9 per 100,000 population). The rate declined by 6.1% per year (95%CI - 6.6 to - 5.5) for adults living with dementia and increased by 1.0% per year (95%CI 0.5-1.5) for adults with no dementia. Multivariable associations identified that adults living with dementia who experienced high frailty and increasing age were between 1.6 and 1.8 times less likely to receive in-hospital rehabilitation. Adults who were living in long-term aged care facilities were between 4.8 and 9.3 times less likely to receive in-hospital rehabilitation which varied by the presence of dementia or delirium. CONCLUSION: Consistent criteria should be applied to determine rehabilitation access, and rehabilitation services designed for older adults living with dementia or in aged care are needed. HIGHLIGHTS: • Adults living with dementia were able to make functional gains following hip fracture rehabilitation. • Need to determine consistent criteria to determine access to hip fracture rehabilitation. • Rehabilitation services specifically designed for adults living with dementia or in aged care are needed.

The effect of a multidisciplinary care bundle on the incidence of delirium after hip fracture surgery: a quality improvement study.

Delirium is a common complication following hip fracture surgery. We introduced a peri-operative care bundle that standardised management in the emergency department, operating theatre and ward. This incorporated: use of fascia iliaca blocks; rationalisation of analgesia; avoidance of drugs known to trigger delirium; a regular education program for staff; and continuous auditing of compliance. The study was conducted between June 2017 and December 2018. We recruited 150 patients before (control group) and 150 patients after (care bundle group) the introduction of the care bundle. In patients having surgery for a hip fracture, there was a lower incidence of delirium on the third postoperative day in the care bundle group compared with the control group (33 patients (22%) vs. 49 patients (33%)), respectively; p = 0.04). Patients in the care bundle group had an adjusted OR of 2.2 (95%CI 1.1-4.4) (p = 0.03) for the avoidance of delirium on the third postoperative day. There was no difference between groups for the secondary outcome measures (measured at 30 days postoperatively) including: all-cause mortality; composite morbidity; institutionalisation; and walking status. During the study period, compliance with elements of the care bundle improved in the emergency department (49 patients (33%) compared with 85 patients (59%); p < 0.001) and anaesthetic department (40 patients (27%) compared with 104 patients (69%); p < 0.001), while orthogeriatrics maintained a high level of compliance (140 patients (93%) compared with 143 patients (95%); p = 0.45). There was a clinically and statistically significant reduction in the incidence of delirium following hip fracture surgery in patients treated with a multidisciplinary care bundle.

A controlled before-after study to evaluate the effect of a clinician led policy to reduce knee arthroscopy in NSW.

BACKGROUND: Clinical evidence shows knee arthroscopy has little benefit for degenerative conditions and considerable variation in the incidence of knee arthroscopy in Australia has been identified. This study aimed to evaluate a clinician-led evidence-based policy which was implemented in one local health district in New South Wales (NSW) in 2012 to reduce the use of knee arthroscopy for patients aged 50 years or over. METHODS: Trends in rates and volume of knee arthroscopy for patients 50 years or over in NSW between 2004 and 2015 by district were examined. Changes at four hospitals that adopted the policy were assessed by a quasi-experimental before and after study design with control groups, using the generalised estimating equations (GEE) Poisson model. Each case hospital was matched with four control hospitals in terms of the volume of knee arthroscopy surgeries performed in the five years prior to the intervention. RESULTS: Between 2004 and 2015, the number of knee arthroscopies in NSW initially increased and then decreased after 2011, with considerable variation across districts. While an overall reducing trend in NSW was observed between 2011 and 2015 (39%), a 58% reduction (95% CI: 55-62%) was found in the intervention district, including the private sector, being the greatest reduction found in all districts. The GEE Poisson results show that, compared with control hospitals, the number of knee arthroscopy was significantly reduced by 56% (95% CI: 11%-79%) at four hospitals that adopted the policy during the follow-up period (p = 0.02). CONCLUSIONS: Clinicians in one local health district initiated a policy to restrict knee arthroscopy for patients aged 50 years or over, which may explain the greater reduction seen in that district compared to all others, despite an overall decrease noted in the state. A significant reduction found at intervened hospitals proved the effect of the policy, suggesting that the implementation of a simple clinical governance process may help reduce inappropriate surgery.

An equivalence study: Are patient-completed and telephone interview equivalent modes of administration for the EuroQol survey?

BACKGROUND: To determine if the EuroQol Health Related Quality of Life survey produces equivalent results when administered by phone interview or patient-completed forms. METHODS: People awaiting hip or knee arthroplasty at a major metropolitan hospital participated. They were randomly assigned to receive the EuroQol Health Related Quality of Life survey via telephone, followed by a patient completed form 1 week later, or vice versa. Equivalence was determined using two one-sided tests (TOST) based on minimal clinically-important differences for the visual analogue scale (VAS) and the summary Utility Index. Cohen's Kappa scores were computed to determine agreement for the individual EuroQoL Likert scale items. RESULTS: Seventy-six from 90 (84%) participants completed the survey twice. Based on limits set at ±7 and ±0.11 for the VAS and Utility Index, respectively, equivalence was established between the two methods of administration for both the VAS (mean difference 0.05 [90% CI -3.76-3.67]) and the Utility Index (mean difference 0.06 [90% CI 0.02-0.11]). Varying levels of agreement, ranging from slight to substantial (κ = 0.17-0.67), were demonstrated for the individual health domains. The order of telephone and patient-completed survey administration had no significant effect on results. CONCLUSIONS: Equivalent results are obtained between telephone and patient-completed administration for the VAS and Utility Index of the EuroQol Survey in people with advanced hip or knee osteoarthritis. The limits of agreement for the individual health domains vary which prevents the accurate interpretation of real change in these items across modes.

Development of quality measurement instruments for root canal treatment.

AIM: To devise measurement instruments for 'quality' of root canal treatment to assess training and outcome of general dental practitioners working within primary care settings. METHOD: Scoring systems relating to quality of root canal treatment were developed using expert consensus and published literature. Domains scored included the Treatment Process, Quality of the Obturation, Clinical Healing, Radiographic Healing and Tooth Complexity. Scoring systems were applied to 10 clinical cases treated by each dentist at the beginning and 10 cases treated at the end of their clinical training and 135 cases treated after completion of training. The dentists recorded the treatment process and clinical healing in clinical logs. Two examiners independently scored the radiographs after undertaking calibration and training. Inter- and intra-examiner reliability of scoring radiographic outcomes was tested using Cohen's Kappa statistics. RESULTS: An instrument was created with four domains to assess quality (two for process and two for outcome of root canal treatment), and a measure of case complexity. Domains of treatment process (n = 240 teeth), outcome (n = 32 teeth) and complexity (n = 215 teeth) were scored using radiographs. The Kappa scores for intra-examiner reliability between 0.22 and 1, whilst inter-examiner reliability ranged between 0.18 and 0.99. CONCLUSION: Evidence-based scores for assessment of the quality (process and outcome) and complexity (structure) of root canal treatment were devised. They were reliable, provided that clinicians were trained in record keeping and examiners have in depth training and calibration in the use of the instruments.

Mail versus telephone administration of the Oxford Knee and Hip Scores.

Telephone and postal methods of administration of the Oxford Knee Score (OKS) and the Oxford Hip Score (OHS) were compared on 85 and 61 patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA), respectively. The test for equivalence was significant for both the knee (P<0.001) and hip participants (P<0.001) indicating that the modes of administration yielded similar results. The ICCs of the OKS and OHS were 0.79 (95% Confidence Interval (CI) 0.70, 0.86) and 0.87 (0.79, 0.92) respectively. The 95% limits of agreement were wide for both scores (OKS LOA, -8.6, 8.2; OHS LOA, -7.7, 5.3). The two modes of administration of the OKS and OHS produce equivalent survey responses at a group level but the same method of administration should be constant for individual monitoring in a clinical setting.

Blended distance education program for junior doctors working in rural hospitals in India.

CONTEXT: Distance learning, supported with supervised clinical work, has been successful in helping doctors located in remote rural areas to practice effectively. Graduates of Christian Medical College (CMC), Vellore, India, have a 2-year service obligation to work in small hospitals mainly located in rural areas. The Fellowship in Secondary Hospital Medicine (FSHM) program is a year-long blended on-site and distance learning program, designed by CMC to support and provide education opportunities for its recent graduates working in small hospitals in rural areas. The FSHM program was designed to help junior doctors develop the knowledge and skills to practice effectively in rural hospitals. ISSUES: The FSHM program consists of 15 paper-based distance learning modules focused on helping to develop knowledge to practice in rural hospitals; three contact sessions at CMC, which focused on developing the necessary skills; project work focused on improving local health services; and networking between peers and with faculty. Two years after implementation of the FSHM program in 2007, the vast majority of students (81%) and faculty (80%) rated the distance learning modules as very good or excellent in helping students develop the knowledge to practice in secondary hospitals. Also, most of the students (88%) and faculty (87%) rated the contact sessions as good or very good in helping students to apply what they had learned in secondary hospitals. Focus group discussions revealed that all of the program participants recognized that the distance learning modules and contact sessions helped them in providing patient care in rural hospitals. LESSONS LEARNED: Well-designed distance learning modules, supported with contact sessions by medical school faculty members, help junior doctors to practice effectively in rural hospitals and reduce their isolation.

A networking approach to reduce academic and social isolation for junior doctors working in rural hospitals in India.

INTRODUCTION: Graduates from Christian Medical College (CMC) Vellore face many challenges while doing their service obligation in smaller hospitals, including academic and social isolation. To overcome these challenges, CMC aspired through its Fellowship in Secondary Hospital Medicine (FSHM), a 1-year blended on-site and distance-learning program, to provide academic and social support through networking for junior doctors working in rural areas. The purpose of this paper is to report the evaluation of the networking components of the FSHM program, with a focus on whether it succeeded in providing academic and social support for these junior doctors. METHODS: A mixed method evaluation was done using written surveys for students and faculty and telephone interviews for students. Evidence for validity was gathered for the written survey. Criteria for validity were also applied for the qualitative data analysis. RESULTS: The major strengths of networking with faculty and peers identified were that it provided social support,, academic support through discussion about patient management problems and a variety of cases seen in the hospital, guidance on projects and reminders about deadlines. Recommendations for improvement included use of videoconferencing and Yahoo Groups. CONCLUSION: It is useful to incorporate networking into distance-learning educational programs for providing support to junior doctors working in rural hospitals.

A bisazobenzene crosslinker that isomerizes with visible light.

BACKGROUND: Large conformational and functional changes of azobenzene-modified biomolecules require longer azobenzene derivatives that undergo large end-to-end distance changes upon photoisomerization. In addition, isomerization that occurs with visible rather than UV irradiation is preferred for biological applications. RESULTS: We report the synthesis and characterization of a new crosslinker in which a central piperazine unit links two azobenzene chromophores. Molecular modeling indicates that this crosslinker can undergo a large change in end-to-end distance upon trans,trans to cis,cis isomerization. Photochemical characterization indicates that it does isomerize with visible light (violet to blue wavelengths). However, the thermal relaxation rate of this crosslinker is rather high (τ(½) ~ 1 s in aqueous buffer at neutral pH) so that it is difficult to produce large fractions of the cis,cis-species without very bright light sources. CONCLUSION: While cis-lifetimes may be longer when the crosslinker is attached to a biomolecule, it appears the para-piperazine unit may be best suited for applications where rapid thermal relaxation is required.

Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro.

The emergence of SARS-CoV-2 virus has resulted in a worldwide pandemic, but effective antiviral therapies are not widely available. To improve treatment options, we conducted a high-throughput screen to uncover compounds that block SARS-CoV-2 infection. A minimally pathogenic human betacoronavirus (OC43) was used to infect physiologically-relevant human pulmonary fibroblasts (MRC5) to facilitate rapid antiviral discovery in a preclinical model. Comprehensive profiling was conducted on more than 600 compounds, with each compound arrayed across 10 dose points. Our screening revealed several FDA-approved agents that can attenuate both OC43 and SARS-CoV-2 viral replication, including lapatinib, doramapimod, and 17-AAG. Importantly, lapatinib inhibited SARS-CoV-2 RNA replication by over 50,000-fold. Further, both lapatinib and doramapimod could be combined with remdesivir to improve antiviral activity in cells. These findings reveal novel therapeutic avenues that could limit SARS-CoV-2 infection.

Endocrinology of the ageing female; the hypothalamic-pituitary-ovarian axis.

The hypothalamic-pituitary-ovarian (HPO) axis goes through a series of complicated, but well coordinated changes as a women enters the menopausal transition. The reproductive consequences of these changes are obvious, but there are also a number of general health consequences as well. As our understanding of the complex inter-workings of the HPO axis evolves, we will be better able to predict menopausal events and create strategies and treatments to optimize women's health as the progress through the menopausal transition.

Quantifying the frequency and volume of urine deposition by grazing sheep using tri-axial accelerometers.

Urine patches deposited in pasture by grazing animals are sites of reactive nitrogen (N) loss to the environment due to high concentrations of N exceeding pasture uptake requirements. In order to upscale N losses from the urine patch, several urination parameters are required, including where, when and how often urination events occur as well as the volume and chemical composition. There are limited data available in this respect, especially for sheep. Here, we seek to address this knowledge gap by using non-invasive sensor-based technology (accelerometers) on ewes grazing in situ, using a Boolean algorithm to detect urination events in the accelerometer signal. We conducted an initial study with penned Welsh Mountain ewes (n = 5), with accelerometers attached to the hind, to derive urine flow rate and to determine whether urine volume could be estimated from ewe squat time. Then accelerometers attached to the hind of Welsh Mountain ewes (n = 30 at each site) were used to investigate the frequency of sheep urination events (n = 35 946) whilst grazing two extensively managed upland pastures (semi-improved and unimproved) across two seasons (spring and autumn) at each site (35-40 days each). Sheep urinated at a frequency of 10.2 ± 0.2 and 8.1 ± 0.3 times per day in the spring and autumn, respectively, while grazing the semi-improved pasture. Urination frequency was greater (19.0 ± 0.4 and 15.3 ± 0.3 times per day in the spring and autumn, respectively) in the unimproved pasture. Ewe squat duration could be reliably used to predict the volume of urine deposited per event and was thus used to estimate mean daily urine production volumes. Sheep urinated at a rate of 16.6 mL/s and, across the entire dataset, sheep squatted for an average of 9.62 ± 0.03 s per squatting event, producing an estimated average individual urine event volume of 159 ± 1 mL (n = 35 946 events), ranging between 17 and 745 mL (for squat durations of 1 to 45 s). The estimated mean daily urine volume was 2.15 ± 0.04 L (n = 2 669 days) across the entire dataset. The data will be useful for modelling studies estimating N losses (e.g. ammonia (NH3) volatilisation, nitrous oxide (N2O) emission via nitrification and denitrification and nitrate (NO3-) leaching) from urine patches.

Practice variation in total hip arthroplasty versus hemiarthroplasty for treatment of fractured neck of femur in Australia.

AIMS: Displaced femoral neck fractures (FNF) may be treated with partial (hemiarthroplasty, HA) or total hip arthroplasty (THA), with recent recommendations advising that THA be used in community-ambulant patients. This study aims to determine the association between the proportion of FNF treated with THA and year of surgery, day of the week, surgeon practice, and private versus public hospitals, adjusting for known confounders. PATIENTS AND METHODS: Data from 67 620 patients in the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 1999 to 2016 inclusive were used to generate unadjusted and adjusted analyses of the associations between patient, time, surgeon and institution factors, and the proportion of FNF treated with THA. RESULTS: Overall, THA was used in 23.7% of patients. THA was more frequently used over time, in younger patients, in healthier patients, in cases performed on weekdays (adjusted odds ratio (OR) 1.27; 95% confidence interval (CI) 1.14 to 1.41), in private hospitals (adjusted OR 4.34; 95% CI 3.94 to 4.79) and by surgeons whose hip arthroplasty practice has a relatively higher proportion of elective patients (adjusted OR 1.65; 95% CI 1.49 to 1.83). CONCLUSION: Practice variation exists in the proportion of FNF patients treated with THA due to variables other than patient factors. This may reflect variation in resources available and surgeon preference, and uncertainty regarding the relative indication.