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Showing papers by "Geelong Football Club published in 2020"


Journal ArticleDOI
23 Sep 2020-Nature
TL;DR: The findings of a World Health Organization expert working group that is developing animal models to test vaccines and therapeutic agents for the treatment of COVID-19, and their relevance for preclinical testing, are reviewed.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.

630 citations




Journal ArticleDOI
TL;DR: This work shows detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection and provides evidence for their nuclease resistance and protection by cellular membranes suggesting that detection of subgenomics RNAs may not be a suitable indicator of active coronavirus replication/infection.
Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first detected in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. Here we show detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection and provide evidence for their nuclease resistance and protection by cellular membranes suggesting that detection of subgenomic RNAs in such samples may not be a suitable indicator of active coronavirus replication/infection.

227 citations


Journal ArticleDOI
TL;DR: Despite the rapid growth and uptake of the positive psychological perspective by researchers and general audiences, hype regarding the field's potential can lead to exaggerated claims, over-inflate....
Abstract: Despite the rapid growth and uptake of the positive psychological perspective by researchers and general audiences, hype regarding the field’s potential can lead to exaggerated claims, over-inflate...

88 citations


Journal ArticleDOI
TL;DR: A basic introduction to the concepts of artificial intelligence is presented as well as an overview of the current research into artificial intelligence in dermatology, examining both its current applications and its future potential.
Abstract: Although artificial intelligence has been available for some time, it has garnered significant interest recently and has been popularized by major companies with its applications in image identification, speech recognition and problem solving. Artificial intelligence is now being increasingly studied for its potential uses in medicine. A sound understanding of the concepts of this emerging field is essential for the dermatologist as dermatology has abundant medical data and images that can be used to train artificial intelligence for patient care. There are already a number of artificial intelligence studies focusing on skin disorders such as skin cancer, psoriasis, atopic dermatitis and onychomycosis. This article aims to present a basic introduction to the concepts of artificial intelligence as well as present an overview of the current research into artificial intelligence in dermatology, examining both its current applications and its future potential.

80 citations


Journal ArticleDOI
TL;DR: An update of the pathobiology, epidemiology, diagnostics, control, and “One Health” implications of WNV infection and disease is given.
Abstract: West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. Infections are associated with economic losses, mainly due to the cost of treatment of infected patients, control programmes, and loss of animals and animal products. The pathogenesis of WNV has been extensively investigated in natural hosts as well as in several animal models, including rodents, lagomorphs, birds, and reptiles. However, most of the proposed pathogenesis hypotheses remain contentious, and much remains to be elucidated. At the same time, the unavailability of specific antiviral treatment or effective and safe vaccines contribute to the perpetuation of the disease and regular occurrence of outbreaks in both endemic and non-endemic areas. Moreover, globalisation and climate change are also important drivers of the emergence and re-emergence of the virus and disease. Here, we give an update of the pathobiology, epidemiology, diagnostics, control, and “One Health” implications of WNV infection and disease.

61 citations


Journal ArticleDOI
TL;DR: Considering the lack of evidence to support any improvements in running economy, combined with the associated shift in loading profile found in this review, changing strike pattern cannot be recommended for an uninjured RFS runner.
Abstract: Running participation continues to increase. The ideal strike pattern during running is a controversial topic. Many coaches and therapists promote non-rearfoot strike (NRFS) running with a belief that it can treat and prevent injury, and improve running economy. The aims of this review were to synthesise the evidence comparing NRFS with rearfoot strike (RFS) running patterns in relation to injury and running economy (primary aim), and biomechanics (secondary aim). Systematic review and meta-analysis. Consideration was given to within participant, between participant, retrospective, and prospective study designs. MEDLINE, EMBASE, CINAHL, and SPORTDiscus. Fifty-three studies were included. Limited evidence indicated that NRFS running is retrospectively associated with lower reported rates of mild (standard mean difference (SMD), 95% CI 3.25, 2.37–4.12), moderate (3.65, 2.71–4.59) and severe (0.93, 0.32–1.55) repetitive stress injury. Studies prospectively comparing injury risk between strike patterns are lacking. Limited evidence indicated that running economy did not differ between habitual RFS and habitual NRFS runners at slow (10.8–11.0 km/h), moderate (12.6–13.5 km/h), and fast (14.0–15.0 km/h) speeds, and was reduced in the immediate term when an NRFS-running pattern was imposed on habitual RFS runners at slow (10.8 km/h; SMD = − 1.67, − 2.82 to − 0.52) and moderate (12.6 km/h; − 1.26, − 2.42 to − 0.10) speeds. Key biomechanical findings, consistently including both comparison between habitual strike patterns and following immediate transition from RFS to NRFS running, indicated that NRFS running was associated with lower average and peak vertical loading rate (limited-moderate evidence; SMDs = 0.72–2.15); lower knee flexion range of motion (moderate-strong evidence; SMDs = 0.76–0.88); reduced patellofemoral joint stress (limited evidence; SMDs = 0.63–0.68); and greater peak internal ankle plantar flexor moment (limited evidence; SMDs = 0.73–1.33). The relationship between strike pattern and injury risk could not be determined, as current evidence is limited to retrospective findings. Considering the lack of evidence to support any improvements in running economy, combined with the associated shift in loading profile (i.e., greater ankle and plantarflexor loading) found in this review, changing strike pattern cannot be recommended for an uninjured RFS runner. CRD42015024523.

54 citations


Journal ArticleDOI
TL;DR: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020).
Abstract: OBJECTIVES: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020, these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, who drew on their expertise and clinical experience. Therefore, this guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression. RESULTS: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of ECT, and discusses how to approach non-response. CONCLUSIONS: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg2020 . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.

52 citations


Journal ArticleDOI
TL;DR: The study showed that the abundance and number of avian picornaviruses and parvoviruses varied considerably throughout the year, with the high number of virus reads in some of the duck samples highly suggestive of an active infection at the time of sampling.
Abstract: Ducks can shed and disseminate viruses and thus play a role in cross-species transmission. In the current study, we detected and characterised various avian parvoviruses and picornaviruses from wild Pacific black ducks, Chestnut teals, Grey teals and Wood ducks sampled at multiple time points from a single location using metagenomics. We characterised 46 different avian parvoviruses belonging to three different genera Dependoparvovirus, Aveparvovirus and Chaphamaparvovirus, and 11 different avian picornaviruses tentatively belonging to four different genera Sicinivirus, Anativirus, Megrivirus and Aalivirus. Most of these viruses were genetically different from other currently known viruses from the NCBI dataset. The study showed that the abundance and number of avian picornaviruses and parvoviruses varied considerably throughout the year, with the high number of virus reads in some of the duck samples highly suggestive of an active infection at the time of sampling. The detection and characterisation of several parvoviruses and picornaviruses from the individual duck samples also suggests co-infection, which may lead to the emergence of novel viruses through possible recombination. Therefore, as new and emerging diseases evolve, it is relevant to explore and monitor potential animal reservoirs in their natural habitat.

50 citations


Journal ArticleDOI
TL;DR: The ability of dogs to sustain prolonged periods of rickettsemia, ability to remain asymptomatically infected with normal haematological parameters and ability to act as biological vehicles for the horizontal transmission of R. felis between infected and uninfected fleas provides indication of their status as a mammalian reservoir of this emerging zoonosis.
Abstract: Rickettsia felis is an obligate intracellular bacterium that is being increasingly recognized as an etiological agent of human rickettsial disease globally. The agent is transmitted through the bite of an infected vector, the cat flea, Ctenocephalides felis, however there is to date, no consensus on the pathogen's vertebrate reservoir, required for the maintenance of this agent in nature. This study for the first time, demonstrates the role of the domestic dog (Canis familiaris) as a vertebrate reservoir of R. felis. The ability of dogs to sustain prolonged periods of rickettsemia, ability to remain asymptomatically infected with normal haematological parameters and ability to act as biological vehicles for the horizontal transmission of R. felis between infected and uninfected fleas provides indication of their status as a mammalian reservoir of this emerging zoonosis.

Journal ArticleDOI
TL;DR: The Reef Life Survey (RLS) as mentioned in this paper provides a new model for ecological monitoring through training experienced recreational divers in underwater visual census methods to the level of skilled scientists, at low cost to allow global coverage.

Journal ArticleDOI
TL;DR: Low muscle strength and slower gait speed, rather than low lean mass, were associated with poor cognition in older men, according to multivariable models.
Abstract: We aimed to examine muscle strength, function and mass in relation to cognition in older men. This cross-sectional data-set included 292 men aged ≥60 yr. Handgrip strength (kg) was measured by dynamometry, gait speed by 4-metre walk (m/s) and appendicular lean mass (kg) by dual-energy x-ray absorptiometry. Cognition was assessed across four domains: psychomotor function, attention, visual learning and working memory. Composite scores for overall cognition were calculated. Bivariate analyses indicated that handgrip strength and gait speed were positively associated with cognitive function. After accounting for confounders, positive associations between individual muscle (or physical) measures and cognitive performance were sustained for handgrip strength and psychomotor function, gait speed and psychomotor function, gait speed and attention, handgrip strength and overall cognition, and gait speed and overall cognition. In multivariable models, handgrip strength and gait speed independently predicted psychomotor function and overall cognition. No associations were detected between lean mass and cognition after adjusting for confounders. Thus, low muscle strength and slower gait speed, rather than low lean mass, were associated with poor cognition in older men.

Journal ArticleDOI
TL;DR: This study demonstrates that mHealth psychological interventions are an effective treatment option for caregivers experiencing high levels of stress.
Abstract: Background: Caregivers play a pivotal role in maintaining an economically viable health care system, yet they are characterized by low levels of psychological well-being and consistently report unmet needs for psychological support. Mobile app–based (mobile health [mHealth]) interventions present a novel approach to both reducing stress and improving well-being. Objective: This study aims to evaluate the effectiveness of a self-guided mobile app–based psychological intervention for people providing care to family or friends with a physical or mental disability. Methods: In a randomized, single-blind, controlled trial, 183 caregivers recruited through the web were randomly allocated to either an intervention (n=73) or active control (n=110) condition. The intervention app contained treatment modules combining daily self-monitoring with third-wave (mindfulness-based) cognitive-behavioral therapies, whereas the active control app contained only self-monitoring features. Both programs were completed over a 5-week period. It was hypothesized that intervention app exposure would be associated with decreases in depression, anxiety, and stress, and increases in well-being, self-esteem, optimism, primary and secondary control, and social support. Outcomes were assessed at baseline, postintervention, and 3-4 months postintervention. App quality was also assessed. Results: In total, 25% (18/73) of the intervention participants were lost to follow-up at 3 months, and 30.9% (34/110) of the participants from the wait-list control group dropped out before the postintervention survey. The intervention group experienced reductions in stress (b=−2.07; P=.04) and depressive symptoms (b=−1.36; P=.05) from baseline to postintervention. These changes were further enhanced from postintervention to follow-up, with the intervention group continuing to report lower levels of depression (b=−1.82; P=.03) and higher levels of emotional well-being (b=6.13; P<.001), optimism (b=0.78; P=.007), self-esteem (b=−0.84; P=.005), support from family (b=2.15; P=.001), support from significant others (b=2.66; P<.001), and subjective well-being (b=4.82; P<.001). On average, participants completed 2.5 (SD 1.05) out of 5 treatment modules. The overall quality of the app was also rated highly, with a mean score of 3.94 out of a maximum score of 5 (SD 0.58). Conclusions: This study demonstrates that mHealth psychological interventions are an effective treatment option for caregivers experiencing high levels of stress. Recommendations for improving mHealth interventions for caregivers include offering flexibility and customization in the treatment design. Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN12616000996460; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371170


Journal ArticleDOI
TL;DR: Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in the authors' cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glau coma after MYOC.

Journal ArticleDOI
TL;DR: Normative data for HGS and MQ are developed, age‐related prevalence of low HGS is reported, and the relationship with age, anthropometry, and body composition for women in Australia is determined.
Abstract: BACKGROUND Low handgrip strength (HGS) is a measure of poor skeletal muscle performance and a marker of ill health and frailty. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We aimed to develop normative data for HGS and MQ, report age-related prevalence of low HGS and MQ, and determine the relationship with age, anthropometry, and body composition for women in Australia. METHODS This cross-sectional analysis included data from 792 women (ages 28-95 years) assessed by the Geelong Osteoporosis Study. Duplicate measures of HGS were performed for each hand with a dynamometer (Jamar) and the mean of maximum values used for analyses. Dual energy X-ray absorptiometry-derived lean mass for the arms was used to calculate MQ as HGS/lean mass (kg/kg). Body mass index (BMI) was categorized as normal (BMI 30.0 kg/m2 ). Fat mass index (FMI) was calculated as whole body fat/height2 (kg/m2 ) and appendicular lean mass index (ALMI) as lean mass of arms and legs/height2 (kg/m2 ). RESULTS Mean (±SD) of HGS values for normal BMI, overweight, and obese groups were 25 (±7), 24 (±7), and 24 (±7) kg, P = 0.09, and for MQ, 12 (±3), 11 (±3), and 10 (±3) kg/kg, P < 0.001. Our data indicated a quadratic relationship between age and HGS or MQ. Mean HGS and MQ remained stable until the fifth age decade then declined steadily with increasing age; therefore, we used data for women (n = 283) aged 28-49 years as the young adult reference group, with mean (SD) values for HGS 28 (±6) kg and MQ 12 (±3) kg/kg. The prevalence of low (T-score < -2) HGS and MQ for women 80 years and older was 52.2% and 39.6%, respectively. In multivariable models, age-adjusted HGS was associated with FMI (B = -0.13, P = 0.004) and ALMI (1.03, <0.001) while age-adjusted MQ was associated with BMI (-0.15, <0.001) but not with FMI. In a sensitivity analysis, the same pattern remained after the removal of 129 women who reported hand and/or arm pain. CONCLUSIONS Mean HGS and MQ declined with advancing age in older women. Our data suggest that while mean HGS increased with appendicular lean mass and decreased with body fat mass, there was no association with BMI. By contrast, MQ decreased with increasing BMI, but not with increasing adiposity.

Journal ArticleDOI
TL;DR: In this article, the authors explore how teachers perceive creative students and what are the commonalities and specificities of such perception among teachers from different countries, including Australia, Italy, Poland, and the United Kingdom.

Journal ArticleDOI
TL;DR: A critical need exists for innovative approaches that address the consumption and wastage of water by dialysis to be sustainable, and water scarcity is increasing globally.
Abstract: Current dialysis technologies require vast quantities of pure water; however, water is a finite resource and water scarcity is increasing globally. For dialysis to be sustainable, a critical need exists for innovative approaches that address the consumption and wastage of water by dialysis.

Journal ArticleDOI
TL;DR: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab‐exposed infants is unknown.
Abstract: Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance. Methods: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: −0.33 to −0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.

Posted ContentDOI
16 Aug 2020-medRxiv
TL;DR: Evidence is presented that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.
Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, provide evidence for their nuclease resistance and likely protection by cellular membranes consistent with being part of virus-induced replication organelles. Furthermore, we show that the ratios of genomic to subgenomic RNA as well as the ratios of plus to negative strand RNA of genomic and subgenomic RNA are consistent with what have been detected for other coronaviruses in cell culture; albeit with the caveat that in vivo diagnostic samples, even in relatively early infection, the ratios of these RNAs are most reminiscent of late culture, semi-purified virus preparations shown to have a relatively constant ratio of genomic to subgenomic RNAs of around 5-10 or higher, while the ratios of positive to negative strands are more than 100 for the genomic RNA and around 20 for the subgenomic RNAs. Overall, our results may help explain the extended PCR positivity of some samples, and may also, at least in part, help explain discrepancies in results of different diagnostic PCR methods described by others; in particular for samples with a low virus load or of poor quality. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.

Journal ArticleDOI
07 Apr 2020
TL;DR: The relative nature of health biomarkers is emphasized, the literature surrounding the classification of relative data is discussed, and how different transformations perform for regularized logistic regression across multiple biomarker types is benchmarked.
Abstract: Since the turn of the century, technological advances have made it possible to obtain the molecular profile of any tissue in a cost-effective manner. Among these advances are sophisticated high-throughput assays that measure the relative abundances of microorganisms, RNA molecules, and metabolites. While these data are most often collected to gain new insights into biological systems, they can also be used as biomarkers to create clinically useful diagnostic classifiers. How best to classify high-dimensional -omics data remains an area of active research. However, few explicitly model the relative nature of these data and instead rely on cumbersome normalizations. This report (i) emphasizes the relative nature of health biomarkers, (ii) discusses the literature surrounding the classification of relative data, and (iii) benchmarks how different transformations perform for regularized logistic regression across multiple biomarker types. We show how an interpretable set of log contrasts, called balances, can prepare data for classification. We propose a simple procedure, called discriminative balance analysis, to select groups of 2 and 3 bacteria that can together discriminate between experimental conditions. Discriminative balance analysis is a fast, accurate, and interpretable alternative to data normalization. IMPORTANCE High-throughput sequencing provides an easy and cost-effective way to measure the relative abundance of bacteria in any environmental or biological sample. When these samples come from humans, the microbiome signatures can act as biomarkers for disease prediction. However, because bacterial abundance is measured as a composition, the data have unique properties that make conventional analyses inappropriate. To overcome this, analysts often use cumbersome normalizations. This article proposes an alternative method that identifies pairs and trios of bacteria whose stoichiometric presence can differentiate between diseased and nondiseased samples. By using interpretable log contrasts called balances, we developed an entirely normalization-free classification procedure that reduces the feature space and improves the interpretability, without sacrificing classifier performance.

Journal ArticleDOI
TL;DR: The authors found that although mathematical creativity increases from year to year, there is a significant within-year decline in creativity, suggesting that it is driven by a combination of environmental, personal, and process-related factors present in the context of school education.

Journal ArticleDOI
TL;DR: Tofacitinib demonstrated treatment effectiveness and persistence similar to bDMARDs, and the study suggests that tofac itinib is an effective and enduring intervention in RA with tofacit inib persistence and effectiveness comparable to b DMARDs.
Abstract: The aim of this study was to describe the real-world evidence for effectiveness, treatment persistence, and treatment patterns among patients in the community with rheumatoid arthritis treated with the JAK inhibitor tofacitinib. This was a retrospective, non-interventional cohort study that extracted data for new users of tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) from the Australian Optimizing Patient outcomes in Australian RheumatoLogy (OPAL) dataset between March 2015 and September 2018. Patients were propensity score matched at a 1:2 tofacitinib to bDMARD ratio based on age, sex, and selected baseline treatment combinations. Treatment effectiveness was evaluated using disease status measures. Treatment persistence was calculated and the percentage of patients receiving monotherapy or combination therapy at treatment initiation was evaluated. Data from 2810 patients were extracted and 1950 patients were included in the matched population (1300 bDMARD initiators and 650 tofacitinib initiators). Patients were predominantly aged 55 to 74 years (57.8%) and female (81.2%). After 18 months of treatment, 52.4% and 57.8% of patients had achieved disease activity score (DAS) remission in the bDMARD and tofacitinib groups, respectively. The median treatment persistence for tofacitinib was similar to that for bDMARDs: 34.2 months (95% CI 32.2 to not reached) and 33.8 months (95% CI 28.8 to 40.4), respectively. In the overall population, more patients were prescribed tofacitinib as monotherapy (43.4%) compared with bDMARD monotherapy (33.4%). Tofacitinib demonstrated treatment effectiveness and persistence similar to bDMARDs. Overall, there was a trend for more use of tofacitinib as monotherapy than bDMARDs.

Journal ArticleDOI
TL;DR: The authors review the current literature and provide their consensus recommendations for minimising adverse outcomes when treating patients with botulinum toxin or hyaluronic acid fillers.
Abstract: Facial aesthetic treatment with injectable neuromodulators and hyaluronic acid fillers is well established, with favourable safety profiles and consistent outcomes. As with any medical treatment, adverse events and complications may occur. Adverse events associated with these products are typically transient and mild to moderate in severity. Serious adverse events, such as infection and intravascular occlusion, are rare. Proper patient selection, consent and counselling, preparation and impeccable injection technique are important risk reduction strategies. Both clinicians and patients must be alert to the signs and symptoms of complications so that appropriate treatment can be started promptly. In this article, the authors review the current literature and provide their consensus recommendations for minimising adverse outcomes when treating patients with botulinum toxin or hyaluronic acid fillers.

Journal ArticleDOI
06 May 2020-PLOS ONE
TL;DR: Investigation of seroepidemiology of paramyxoviruses and Australian bat lyssavirus in a range-expanding fruit bat, the Grey-headed flying fox, in a new camp in Adelaide, South Australia suggests a common exposure to Hendra virus and other paramyxOViruses in this flying fox camp in South Australia.
Abstract: Habitat-mediated global change is driving shifts in species' distributions which can alter the spatial risks associated with emerging zoonotic pathogens. Many emerging infectious pathogens are transmitted by highly mobile species, including bats, which can act as spill-over hosts for pathogenic viruses. Over three years, we investigated the seroepidemiology of paramyxoviruses and Australian bat lyssavirus in a range-expanding fruit bat, the Grey-headed flying fox (Pteropus poliocephalus), in a new camp in Adelaide, South Australia. Over six, biannual, sampling sessions, we quantified median florescent intensity (MFI) antibody levels for four viruses for a total of 297 individual bats using a multiplex Luminex binding assay. Where appropriate, florescence thresholds were determined using finite mixture modelling to classify bats' serological status. Overall, apparent seroprevalence of antibodies directed at Hendra, Cedar and Tioman virus antigens was 43.2%, 26.6% and 95.7%, respectively. We used hurdle models to explore correlates of seropositivity and antibody levels when seropositive. Increased body condition was significantly associated with Hendra seropositivity (Odds ratio = 3.67; p = 0.002) and Hendra virus levels were significantly higher in pregnant females (p = 0.002). While most bats were seropositive for Tioman virus, antibody levels for this virus were significantly higher in adults (p < 0.001). Unexpectedly, all sera were negative for Australian bat lyssavirus. Temporal variation in antibody levels suggests that antibodies to Hendra virus and Tioman virus may wax and wane on a seasonal basis. These findings suggest a common exposure to Hendra virus and other paramyxoviruses in this flying fox camp in South Australia.

Journal ArticleDOI
01 Jun 2020-Heliyon
TL;DR: ILRUN is characterised as a highly phylogenetically conserved protein containing UBA-like and a NBR1-like domains that are both essential for inhibition of type-I interferon and tumor necrosis factor alpha transcription in human cells.

Journal ArticleDOI
TL;DR: TEDR repair showed improved functional outcomes for tears >3 cm compared with SR repair, and post hoc testing showed that the difference was statistically significant.

Journal ArticleDOI
TL;DR: G germline targeting of the endogenous chicken Interferon Alpha and Beta Receptor Subunit 1 (IFNAR1) gene is reported by in vivo transgenic expression of the high-fidelity Cas9 and guide RNAs (gRNAs) in chickens.
Abstract: Development of simple and readily adoptable methods to mediate germline engineering of the chicken genome will have many applications in research, agriculture and industrial biotechnology. We report germline targeting of the endogenous chicken Interferon Alpha and Beta Receptor Subunit 1 (IFNAR1) gene by in vivo transgenic expression of the high-fidelity Cas9 (Cas9-HF1) and guide RNAs (gRNAs) in chickens. First, we developed a Tol2 transposon vector carrying Cas9-HF1, IFNAR1-gRNAs (IF-gRNAs) and green fluorescent protein (GFP) transgenes (pTgRCG) and validated in chicken fibroblast DF1 cells. Next, the pTgRCG plasmid was directly injected into the dorsal aorta of embryonic day (ED) 2.5 chicken embryos targeting the circulating primordial germ cells (PGCs). The resulting chimera roosters generated a fully transgenic generation 1 (G1) hen with constitutive expression of Cas9-HF1 and IF-gRNAs (G1_Tol2-Cas9/IF-gRNA). We detected a spectrum of indels at gRNA-targeted loci in the G1_Tol2-Cas9/IF-gRNA hen and the indels were stably inherited by the G2 progeny. Breeding of the G1_Tol2-Cas9/IF-gRNA hen resulted in up to 10% transgene-free heterozygote IFNAR1 mutants, following null-segregation of the Tol2 insert. The method described here will provide new opportunities for genome editing in chicken and other avian species that lack PGC culture.

Journal ArticleDOI
TL;DR: Older people and their relatives identified specific elements of care that uphold or threaten dignity during acute hospitalisation and Clinicians may benefit from systematic dignity-related training.
Abstract: Aims and objectives The aim of the study was to enhance understanding about dignified care from older peoples' and their carers' perspectives. The information will contribute to the development of a tool to measure older peoples' dignity during hospitalisation. Background Older people are a vulnerable cohort at risk of loss of dignity during acute hospitalisation arising from environmental, behavioural and patient factors. It is not clear how older people and their relatives define dignified care in acute care settings. Design An interpretative descriptive method was used. Methods A purposive sample of older people (at least 65 years) who had been hospitalised in acute care and subsequently transferred to sub-acute care, and their relatives, were invited to participate. The study was undertaken in one sub-acute ward in a regional healthcare organisation in Victoria, Australia. Individual interviews were audio-recorded then transcribed. Data were analysed using thematic content analysis. The COREQ checklist was used to document reporting of the study. Results Individual interviews were conducted: 24 patients and 12 relatives. Three main themes were identified: "Involve me in decisions about my care and treatment," "Keep me safe when I am vulnerable" and "Treat me as an individual and with respect." Older people want to be involved in decisions about their care and treatment and to receive adequate, suitable information. They feel vulnerable during hospitalisation and want to feel safe when speaking up about concerns. Individual acknowledgement is an important aspect of dignity. Conclusions Older people and their relatives identified specific elements of care that uphold or threaten dignity during acute hospitalisation. Nurses play a major role in upholding dignity for older people in hospital. Relevance to clinical practice Clinicians may benefit from systematic dignity-related training. Specific strategies to enhance older persons' dignity, including communication skills training and continence management need to be developed, implemented and evaluated.