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Abstract Background Patient and public involvement (PPI) in research is widely acknowledged as essential to achieving successful and impactful research. Despite this acknowledgement, there are limited reports on how to approach and apply meaningful PPI throughout the research cycle and how to address challenges for researchers such as doctoral students, particularly when undertaking research on sensitive topics. This paper provides insights and examples for researchers new to PPI, on the impact of active PPI and recommendations for building and developing a PPI group in a paediatric focused doctoral research study with bereaved parents and carers. Methods PPI was informed by the research cycle. The GRIPP2 short-form checklist was used to report PPI. The research was funded by the National Institute for Health and Care Research. Results PPI enhanced the research through input into the study design, recruitment, co-design of the study website and branding; and ethics amendments to increase participation in response to the COVID-19 pandemic. The literature review was extended to incorporate a PPI consultation phase and members contributed to data analysis. A flexible approach enabled involvement to develop iteratively throughout the research study, resulting in changes being made to enhance the study design and outcomes. Conclusion This paper contributes to the limited knowledge base on embedding PPI into a doctoral research study and within the paediatric setting specifically working in partnership with bereaved parents and carers. Employing an adaptive approach to meet individual PPI needs, building a trusting and respectful partnership, creating shared ownership and investment in the research, are essential components to successful PPI.

Not available.

Aim To quantify the impact of the pandemic on fatal burden of disease among those living in residential aged care homes (RACH) in Australia. Methods Using Residential Aged Care data linked to Death Registrations (Jan 2016 to 11 Aug 2022), we estimated years of life lost per person-year (YLL/py) among people living in RACH. Additional linkage of notifications data from the state of Victoria enabled comparisons of average survival times between notified COVID-19 cases and matched non-cases living in RACH using COVID-19. Results COVID-19 deaths were low in 2020 and 2021 (610 and 260 deaths, respectively) but increased in 2022 (3230 deaths). Years of life lost due to COVID-19 was low in 2020 and 2021 (1.2% and 0.5% of the total YLL/py, respectively) but increased substantially in 2022 (8.3% of the total YLL/py). However, there was little evidence that YLLs/py overall increased in the pandemic (range: 0.87 to 0.93 in 2016-2019 and 0.85 to 0.88 in 2020-2022). Results describing differences in survival between notified COVID-19 cases and non-cases are forthcoming. Conclusion We observed no substantial increase in overall fatal burden of disease among the RACH population during the pandemic period. While COVID-19 case numbers increased in 2022 relative to 2020-2021, this was offset with better survival among cases over time, reflecting, at least in part, decreasing disease severity, high uptake of COVID-19 vaccines and antiviral medications.

BackgroundThe Feeling Good App is an automated stand-alone digital mobile mental health tool currently undergoing beta testing with the goal of providing evidence-informed self-help lessons and exercises to help individuals reduce depressive symptoms without guidance from a mental health provider. Users work through intensive basic training (IBT) and ongoing training models that provide education regarding cognitive behavioral therapy principles from a smartphone. ObjectiveThe key objective of this study was to perform a nonsponsored third-party academic assessment of an industry-generated data set; this data set focused on the safety, feasibility, and accessibility of a commercial automated digital mobile mental health app that was developed to reduce feelings associated with depression. MethodsThe Feeling Good App development team created a waitlist cohort crossover design and measured symptoms of depression and anxiety using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and an app-specific measure of negative feelings called the 7 Dimension Emotion Slider (7-DES). The waitlist cohort crossover design divided the participants into 2 groups, where 48.6% (141/290) of the participants were given immediate access to the apps, while 51.4% (149/290) were placed on a 2-week waitlist before being given access to the app. Data collected by the Feeling Good App development team were deidentified and provided to the authors of this paper for analysis through a nonsponsored university data use agreement. All quantitative data were analyzed using SPSS Statistics (version 28.0; IBM Corp). Descriptive statistics were calculated for demographic variables. Feasibility and acceptability were descriptively assessed. All participants included in the quantitative data were given access to the Feeling Good App; this study did not include a control group. ResultsIn terms of safety, there was no statistically significant change in suicidality from preintervention to postintervention time points (t288=0.0; P>.99), and there was a statistically significant decrease in hopelessness from preintervention to postintervention time points (F289=30.16; P

Ischemic colitis is the most common form of gastrointestinal ischemia . The diagnosis of ischemic colitis is made by clinical data and computed tomography (CT) imaging of the abdomen and pelvis . While colonoscopy is considered the gold standard for diagnosis, this is not performed in the emergency department (ED) . Few studies have been performed to describe the sonographic findings of ischemic colitis using point of care ultrasound (POCUS). We report a case that highlights the sonographic findings of ischemic colitis in a patient who had two separate visits to the ED, showcasing the utility of POCUS in making this diagnosis. POCUS can be used as a diagnostic tool for early detection of ischemic colitis leading to prompt treatment with antibiotics, CT imaging, and surgical consultation.

Abstract Paroxysmal nocturnal haemoglobinura is an acquired life‐threatening haemolytic condition, which is generally well controlled with terminal complement blockade with eculizumab. Whilst almost all patients treated with terminal complement inhibitors develop extravascular haemolysis, only a small proportion of these results in symptomatic anaemia limiting their activities and requiring red cell transfusion. This case highlights the potential role for the C3 inhibitor, pegcetacoplan, in controlling both intravascular and extravascular haemolysis, and is the first case to report on the use of additional doses of pegcetacoplan to control breakthrough haemolysis.

Causal machine learning tools are beginning to see use in real-world policy evaluation tasks to flexibly estimate treatment effects. One issue with these methods is that the machine learning models used are generally black boxes, that is, there is no globally interpretable way to understand how a model makes estimates. This is a clear problem for governments who want to evaluate policy as it is difficult to understand whether such models are functioning in ways that are fair, based on the correct interpretation of evidence and transparent enough to allow for accountability if things go wrong. However, there has been little discussion of transparency problems in the causal machine learning literature and how these might be overcome. This article explores why transparency issues are a problem for causal machine learning in public policy evaluation applications and considers ways these problems might be addressed through explainable AI tools and by simplifying models in line with interpretable AI principles. It then applies these ideas to a case study using a causal forest model to estimate conditional average treatment effects for returns on education study. It shows that existing tools for understanding black-box predictive models are not as well suited to causal machine learning and that simplifying the model to make it interpretable leads to an unacceptable increase in error (in this application). It concludes that new tools are needed to properly understand causal machine learning models and the algorithms that fit them.

Abstract A mid-level data fusion coupled with multivariate analysis approach is applied to dual-platform mass spectrometry data sets using Rapid Evaporative Ionization Mass Spectrometry and Inductively Coupled Plasma Mass Spectrometry to determine the correct classification of salmon origin and production methods. Salmon (n = 522) from five different regions and two production methods are used in the study. The method achieves a cross-validation classification accuracy of 100% and all test samples (n = 17) have their origins correctly determined, which is not possible with single-platform methods. Eighteen robust lipid markers and nine elemental markers are found, which provide robust evidence of the provenance of the salmon. Thus, we demonstrate that our mid-level data fusion - multivariate analysis strategy greatly improves the ability to correctly identify the geographical origin and production method of salmon, and this innovative approach can be applied to many other food authenticity applications.

Abstract Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using double allelic homologous recombination. The mutant parasite line failed to replicate when inoculated into host cells in vitro or in mice indicating that Cyp19 is critical for infectivity. The mutant parasite line also fails to replicate in or cause clinical disease in immuno-deficient mice further validating their lack of virulence. Repeated inoculation of mutant parasites into immuno-competent mice elicits parasite-specific trypanolytic antibodies and a Th-1 biased immune response and challenge of mutant immunized mice with virulent wild-type parasites is 100% effective at preventing death from acute disease. These results suggest that parasite Cyp19 may be candidate for small molecule drug targeting and that the mutant parasite line may warrant further immunization studies for prevention of Chagas disease.

Objectives: This study aimed to develop and evaluate a competency of nursing process questionnaire (CNPQ) for registered nurses in Cambodia. Methods: Guided by the nursing process, an initial questionnaire was generated through focus group discussion, literature review, and the expert consultation. Finally, the validity and reliability of the questionnaire were validated through a questionnaire survey online of 260 registered nurses selected from Complimentary Package Activities 1, 2, 3, and national hospitals from January to February 2022 in five geographic areas of Cambodia. Results: The content validity index was 1.00. The Cronbach’s α coefficient for the whole questionnaire was 0.963, and the range for the five dimensions was 0.963–0.964, which shows that the questions were consistent. The test-retest reliability was 0.769. The exploratory factor analysis led to a list of 24 items that were grouped into five dimensions: assessment, diagnosis, planning, implementation, and evaluation. The cumulative variance contribution rate was 70.08%. Conclusions: The CNPQ developed in this study showed good reliability and validity and can be used to assess the competency of registered nurses by themselves and help nursing managers to develop the relevant policies.

Background: Investing in clinical education is important for adult urgent and emergency surgery and traumatology as it promotes registered nurses’ competencies by providing professional development training to respond to urgent or emergency surgeries. Objective: To examine registered nurses' self-assessment of the effects of virtual video simulation with an immediate debriefing approach on nursing process competencies, nursing care quality, incomplete care, and patient safety in surgical units. Methods: This study used a quasi-experimental two-group pre- and post-test design. The study was conducted at two provincial hospitals in Cambodia. Participants included registered nurses employed in surgical units. The experimental group (n = 46) completed a virtual video simulation and immediate debriefing. The control group (n = 35) completed virtual training on the nursing process. Data were collected two months after a successful second-week follow-up using Competency of Nursing Process, Cambodian Nursing Care Quality, Care Left Undone, and Patient Safety scales. Wilcoxon signed-rank test and Mann-Whitney U test were used to evaluate the differences before and after the sessions. Generalized linear model was used to compare the differences between the two groups. Results: The results showed statistically significant improvements in the experimental group on competency, nursing care quality, patient safety, and reducing care left undone after the intervention. However, the control group revealed statistically insignificant differences. In addition, the experimental group provided positive feedback, such as experiencing a real patient scenario, developing critical-thinking, improving communication skills, and having an opportunity to ask questions. Conclusion: Our study showed that VVS and immediate debriefing have the potential to support in-service training of RNs from diverse backgrounds. Particularly, integrating virtual video simulation and immediate debriefing may to promote competency in the nursing process and improve care outcomes.

Abstract The development of horizontal drilling and hydraulic fracking has led to an increase in oil and natural gas extraction. Development of infrastructure to extract and transport these resources is expected to increase over the next few decades, resulting in extensive land disturbance. Although reclamation aims to sufficiently return disturbed lands to their pre‐disturbance use in an ecological sense, reclaimed rights‐of‐ways (ROW) commonly produce reduced crop yields. The objective of this study was to use meta‐analysis to determine soil disturbance trends across studies found in the peer‐reviewed literature. Papers that reported soil property data on disturbed ROWs and adjacent undisturbed sites were retrieved by searching the Web of Science database. Papers were separated by climate regions, resulting in analyses being conducted for studies in semiarid and humid climate regions. Results indicate that soil bulk density, soil organic matter, and pH are significantly increased on reclaimed ROWs. Soil metrics not incorporated in meta‐analysis due to insufficient observations or the possible presence of publication biases like a desire to publish significant results and poor study design (cation exchange capacity, calcium, phosphorus, magnesium, total nitrogen, electrical conductivity, sodium, sodium adsorption ratio, and texture) are assessed and discussed. Best management practices gleaned from studies incorporated into meta‐analysis are discussed to provide strategies to limit soil property disturbances.

Introduction: As the prevalence of patients with left ventricular assist devices (LVAD) presenting to the emergency department (ED) increases, clinicians must be aware of LVAD-associated infections. Case Report: A well-appearing, 41-year-old male with history of heart failure status post prior-LVAD placement presented to the ED for swelling of his chest. What appeared initially as a superficial infection was further assessed with point-of-care ultrasound and found to represent a chest wall abscess involving the driveline, ultimately resulting in sternal osteomyelitis and bacteremia. Conclusion: Point-of-care ultrasound should be considered an important tool in the initial assessment of potential LVAD-associated infection.

Exploring the early development of an area of medical literature can inform contemporary medical debates. Different methods of inference include deduction, induction, abduction, and inference to the best explanation. I argue that early shaken baby research is best understood as using abduction to tentatively suggest that infants with unexplained intracranial and ocular bleeding have been assaulted. However, this tentative conclusion was quickly interpreted, by some at least, as a general rule that infants with these pathological signs were certainly cases of abuse. Rather than focusing on inductive arguments, researchers today may be better off focusing on making a compelling inference to the best explanation.

Abstract This study used desorption electrospray ionisation mass spectrometry (DESI-MS) to analyse and detect and classify biomarkers in five different animal and plant sources of milk for the first time. A range of differences in terms of features was observed in the spectra of cow milk, goat milk, camel milk, soya milk, and oat milk. Chemometric modelling was then used to classify the mass spectra data, enabling unique or significant markers for each milk source to be identified. The classification of different milk sources was achieved with a cross-validation percentage rate of 100% through linear discriminate analysis (LDA) with high sensitivity to adulteration (0.1–5% v/v). The DESI-MS results from the milk samples analysed show the methodology to have high classification accuracy, and in the absence of complex sample clean-up which is often associated with authenticity testing, to be a rapid and efficient approach for milk fraud control.

Abstract Organic food fraud is a significant challenge in the food testing sector—high price premiums, ease of access to produce to be relabelled and difficulties in developing testing strategies that can detect such frauds make organic foods particularly attractive and thus highly vulnerable to fraud. Samples of conventional and organic cattle taken across meat plants in Ireland and the United Kingdom, consisting of the neck (supraspinatus), rump (gluteus), and shin (flexor carpi radialis) regions of the carcass were analysed using a high resolution time-of-flight based rapid evaporative ionisation mass spectrometry (REIMS) system. The resulting untargeted lipidomic data (m/z 600–1000) was used to generate PCA-LDA models for production system and for muscle type, for these models, it was found that the production system model could differentiate organic from conventional beef with an accuracy of 84%, whilst the muscle type model could identify the cut of meat with a 98% accuracy; additionally, samples can be assessed against multiple models simultaneously, reducing analysis time and sample numbers. The use of REIMS showed considerable promise in its ability to detect different forms of meat fraud; its accuracy in differentiating organic from conventional beef is superior to stable isotope ratio mass spectrometry, with the added advantages of substantially shorter analysis times and lower sample analysis costs. The ability to rapidly confirm the cut of meat also demonstrates the potential of REIMS to concurrently determine multiple aspects of beef authenticity in a close to real time analysis.

In this work, we develop a compact, low-power and partially 3D-printed magnetorheological fluid clutch that operates by variably and reversibly altering the shear stress of the fluid through the local activation of an array of electropermanent magnets (EPMs). By toggling the magnetization of each EPM independently on the order of a few milliseconds, we allow for rapid response times and variable torque transmission without further power input. Selectively polarizing the EPMs for different lengths of time results in repeatable and variable magnetic flux, in turn enabling further control precision. We present the design, modeling, and measured performance of this clutch with various control strategies, and demonstrate its utility as a low-power alternative to more traditional clutch designs.

Lyme disease, the most common tick-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi. While most patients with acute Lyme disease recover completely if treated with antibiotics shortly after the onset of infection, approximately 10–30% experience post-treatment symptoms and 5–10% have residual symptoms with functional impairment (post-treatment Lyme disease syndrome or PTLDS). These patients typically experience pain, cognitive problems, and/or fatigue. This narrative review provides a broad overview of Lyme disease, focusing on neuropsychiatric manifestations and persistent symptoms. While the etiology of persistent symptoms remains incompletely understood, potential explanations include persistent infection, altered neural activation, and immune dysregulation. Widely recognized is that new treatment options are needed for people who have symptoms that persist despite prior antibiotic therapy. After a brief discussion of treatment approaches, the article focuses on vagus nerve stimulation (VNS), a neuromodulation approach that is FDA-approved for depression, epilepsy, and headache syndromes and has been reported to be helpful for other diseases characterized by inflammation and neural dysregulation. Transcutaneous VNS stimulates the external branch of the vagus nerve, is minimally invasive, and is well-tolerated in other conditions with few side effects. If well-controlled double-blinded studies demonstrate that transcutaneous auricular VNS helps patients with chronic syndromes such as persistent symptoms after Lyme disease, taVNS will be a welcome addition to the treatment options for these patients.

Gene Oishi’s autobiographical and episodic novel Fox Drum Bebop (2014) will likely be one of the final novels published by someone who was an internee in the detention camps in which the US government imprisoned Japanese Americans during the Second World War. As such, it presents complicated questions about temporality, representation, and the processes of trauma. Through focusing on the protagonist Hiroshi Kono (largely, though not restrictively, based on Oishi’s own life experience) and his siblings who have distinct ideological reactions to their ethnic identity and their wartime experience, Oishi explores how internment at once lasted for a determinate period but continues to extend in space and dilate in time for as long as the memories of it endure. The novel uses the musical aesthetics of jazz as a correlate for this discontinuous processing of experience. Oishi’s narrative asks if those who suffer oppression and trauma can ever find peace, and how, if at all, having a long life and reflecting upon the past can alter one’s sense of what happened.

Objectives In line with affordability and equity principles, Medicare—Australia’s universal public health insurance system—has measures to limit out-of-pocket costs (OOPC), especially among lower income households. We examined the distribution of OOPC for Medicare-subsidised out-of-hospital services and prescription medicines, for Census households, according to their ability to pay. Methods We used 2016 Australian Census data linked to Medicare claims to obtain OOPC for out-of-hospital services and medicines in each household in 2017-18. We derived household disposable income by combining income information from the Census linked to income tax and social security data. All data were available from the Multi-Agency Data Integration Project, enabled through a partnership of various government agencies. We quantified OOPC as a proportion of equivalised household disposable income and calculated Kakwani indices (K) to measure progressivity. We also used linked National Health Survey data to analyse costs separately by chronic conditions. Results We analysed 85% (n=6,830,365) of all Census private households. Overall, OOPC as a percentage of equivalised household disposable income decreased from 1.16% (out-of-hospital services) and 1.35% (prescription medicines) in the poorest decile to 0.63% and 0.34% in the richest decile, respectively. The regressive trend was less pronounced for out-of-hospital services (K = -0.06), with percentage OOPC relatively stable between the 2nd and 9th income deciles; while percentage OOPC decreased steeply with increasing income for medicines (K = -0.24). (Chronic conditions results will be presented—embargoed at time of submission) Conclusion OOPC for out-of-hospital Medicare services were mildly regressive while those for prescription medicines were distinctly regressive. Actions to reduce inequity in OOPC for medicines, such as reducing the co-payments for low income households should be considered.

Introduction Each year, an estimated two million Australians commence opioids, with 50 000 developing longer-term (persistent) opioid use. An estimated 3%–10% of opioid-naïve patients prescribed opioids following surgery develop persistent opioid use. This study will compare rates of persistent opioid use between two commonly used postoperative opioids, oxycodone and tapentadol, to understand if initial postoperative opioid type is important in determining longer-term outcomes.Methods and analysis A retrospective data linkage study that analyses administrative data from hospital and community pharmacies. Data will be obtained from at least four pharmacies that service large hospitals with comparable supplies of oxycodone and tapentadol. The study will include at least 6000 patients who have been dispensed a supply of oxycodone or tapentadol to take home following their discharge from a surgical ward. The primary outcome measure will be persistent opioid use at 3 months postdischarge for opioid naïve people who receive either immediate release tapentadol or immediate release oxycodone. Hierarchical logistic regression models will be used to predict persistent opioid use, controlling for covariates including comorbidities.Ethics and dissemination Ethics approval has been obtained through the Monash University Human Research Ethics Committee (29977). We will present project findings in a peer-reviewed journal article, in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data statement.

Artists, scholars, and popular media often describe James Baldwin as revolutionary, either for his written work or for his role in the civil rights movement. But what does it mean to be revolutionary? This article contends that thoughtlessly calling James Baldwin revolutionary obscures and erases the non-revolutionary strategies and approaches he employed in his contributions to the civil rights movement and to race relations as a whole. Frequent use of revolutionary as a synonym for “great” or “important” creates an association suggesting that all good things must be revolutionary, and that anything not revolutionary is insufficient, effectively erasing an entire spectrum of social and political engagement from view. Baldwin’s increasing relevance to our contemporary moment suggests that his non-revolutionary tactics are just as important as the revolutionary approaches employed by civil rights leaders such as Malcolm X or Martin Luther King, Jr.

Abstract Background The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade. Objective We assessed the association between combined clopidogrel–PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes. Patients and Methods A nested case–control study was conducted within Cerner Corporation’s Health Facts® database. A retrospective cohort of patients who experienced a first MI and started clopidogrel treatment was created. Within this cohort, patients experiencing a second MI (cases) were matched with up to five controls. Logistic regression was used to estimate adjusted odds ratios (aORs). Findings were compared with those obtained from models with three negative control exposure drugs: H2 receptor antagonists, prasugrel, and ticagrelor. Results In total, 2890 recurrent MI cases were identified within 12 months following entry into the cohort of clopidogrel users (N = 52,006). aOR for PPI use versus non-use among clopidogrel users was 1.08 [95% confidence interval (CI) 0.95–1.23]. Similar ORs were obtained for secondary endpoints. A positive association between combined use of clopidogrel/PPIs and increased risk of MI was seen in the group aged 80–89 years (aOR 1.26; 95% CI 1.05–1.51). No associations with MI were observed for (1) H2 receptor antagonist use versus non-use among clopidogrel users or (2) PPI use versus non-use among prasugrel users or among ticagrelor users. Conclusions Overall, our findings do not support a significant adverse clinical impact of concomitant clopidogrel/PPI use by patients with MI. Nonetheless, investigation of the possible association seen in those aged 80–89 years may be warranted.

Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were “disulfiram” and “Antabuse”. Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results: In total, 196 sources addressing our research focus spanning 1948–2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions: While disulfiram has promise as a “repurposed” agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications.

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P–Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P–Br bonds in TAPs as in better known isoelectronic diazaphospholenes.

BackgroundHigh levels of vaccination coverage in populations will be required even with vaccines that have high levels of effectiveness to prevent and stop outbreaks of coronavirus. The World Health Organisation has suggested that governments take a proactive response to vaccine hesitancy 'hotspots' based on social and behavioural insights.MethodsRepresentative longitudinal online survey of over 3000 adults from Australia that examines the demographic, attitudinal, political and social attitudes and COVID-19 health behavior correlates of vaccine hesitance and resistance to a COVID-19 vaccine.ResultsOverall, 59% would definitely get the vaccine, 29% had low levels of hesitancy, 7% had high levels of hesitancy and 6% were resistant. Females, those living in disadvantaged areas, those who reported that risks of COVID-19 was overstated, those who had more populist views and higher levels of religiosity were more likely to be hesitant or resistant while those who had higher levels of household income, those who had higher levels of social distancing, who downloaded the COVID-Safe App, who had more confidence in their state or territory government or confidence in their hospitals, or were more supportive of migration were more likely to intend to get vaccinated.ConclusionsOur findings suggest that vaccine hesitancy, which accounts for a significant proportion of the population can be addressed by public health messaging but for a significant minority of the population with strongly held beliefs, alternative policy measures may well be needed to achieve sufficient vaccination coverage to end the pandemic.

Introduction Describing out-of-pocket (OOP) healthcare costs in relation to ability to pay requires multiple linked data sources not previously available. Current estimates of the progressivity of OOP healthcare costs in Australia are based on self-report surveys. Using newly linked Census to administrative income and medical claims data, we aimed to quantify, for the first time, the progressivity of OOP costs for government-subsidised out-of-hospital healthcare in Australia. Objectives and Approach We used Australian Census 2011 linked to Personal Income Tax (PIT), Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data compiled through the Multi-Agency Data Integration Project (MADIP). Personal disposable income was estimated using a combination of PIT data and Census self-reported income, and aggregated across the household to estimate equivalised household income. We estimated annual MBS (out-of-hospital only) and PBS OOP costs as a proportion of equivalised household income, and assessed progressivity by reporting this for each income decile and computing a Kakwani Index. Results We will present findings on progressivity overall, and separately by age, sex and location (incomplete at time of abstract submission). Conclusion / Implications Our study will present one measure regarding the equity of healthcare costs, and help to identify vulnerable or at-risk groups. These findings may inform policy changes on equity in the financing of healthcare. Newly linked data from the MADIP can be used to relate healthcare costs to ability to pay.

Soft robotics as a field of study incorporates different mechanisms, control schemes, as well as multifunctional materials to realize robots able to perform tasks inaccessible to traditional rigid robots. Conventional methods for controlling soft robots include pneumatic or hydraulic pressure sources, and some more recent methods involve temperature and voltage control to enact shape change. Magnetism was more recently introduced as a building block for soft robotic design and control, with recent publications incorporating magnetorheological fluids and magnetic particles in elastomers, to realize some of the same objectives present in more traditional soft robotics research. This review attempts to organize and emphasize the existing work with magnetism and soft robotics, specifically studies on magnetic elastomers, while highlighting potential avenues for further research enabled by these advances.

Anisotropy and competing exchange interactions have emerged as two central ingredients needed for centrosymmetric materials to exhibit topological spin textures. Fe3Sn2 is thought to have these ingredients as well, as it has recently been discovered to host room temperature skyrmionic bubbles with an accompanying topological Hall effect. We present small-angle inelastic neutron scattering measurements that unambiguously show that Fe3Sn2 is an isotropic ferromagnet below TC≈660 K to at least 480 K—the lower temperature threshold of our experimental configuration. Fe3Sn2 is known to have competing magnetic exchange interactions, correlated electron behavior, weak magnetocrystalline anisotropy, and lattice (spatial) anisotropy; all of these features are thought to play a role in stabilizing skyrmions in centrosymmetric systems. Our results reveal that at the elevated temperatures measured, there is an absence of significant magnetocrystalline anisotropy and that the system behaves as a nearly ideal isotropic exchange interaction ferromagnet, with a spin stiffness D(T=480 K)=168 meV Å2, which extrapolates to a ground state spin stiffness D(T=0 K)=231 meV Å2.

Eve Langley’s The Pea-Pickers is often seem as a quaint artifact of a now-vanished Australia. This paper seeks to rescue the contemporary relevance of this novel of two young women who go into the rural areas of Gippsland to pick peas, showing its pioneering attention to transgender concerns, the polyphonic panoply of its style and soundscape,. and its portrayal of a settler culture not anchored in a perilous identity but dynamically on the move. As so often in settler colony literature, though, rigidities on the issue of race—particularly the portrayal of the Muslim migrant Akbarah Khan—mar the canvas, and make Langley’s novel as emblematic of the constitutive problems of Australian literary history as of its artistic achievements. Just as Langley’s gender variance and personal nonconformity made her an outlier in the Austrlaia and New Zealand she lived in, so is her contribution to Australian literature an unfinished project.

Despite huge sales and publicity on its issuance in 2004, Susanna Clarke’s Jonathan Strange & Mr Norrell has received comparatively little sustained critical attention. This article argues that much of this neglect proceeds from assumptions that the book is nostalgic for a sovereign magic, when in fact its historicity is a way of shaking up time itself. I argue Clarke is looking to the early nineteenth century as the earliest possible modernity, a time in which magic is intertwined with the world much as it would be today if magic arose now. Examining the sociable magician Norrell, the questionably resurgent medieval king John Uskglass and the African-descended manservant Stephen Black provide different models of what the interrelationship between magic and reality can be and serve to destabilize any sense of a sovereign past in the book. The book’s plural magical modernity’s counter any atavistic sovereignty. By taking the reading of Clarke’s novel beyond nostalgic sovereignty, one can understand how it participates in the twenty-first century revaluation of fantasy as politically progressive and epistemically radical.

BackgroundMagnetic resonance imaging (MRI) of the knee is the preferred method for diagnosing knee injuries. However, interpretation of knee MRI is time-intensive and subject to diagnostic error and variability. An automated system for interpreting knee MRI could prioritize high-risk patients and assist clinicians in making diagnoses. Deep learning methods, in being able to automatically learn layers of features, are well suited for modeling the complex relationships between medical images and their interpretations. In this study we developed a deep learning model for detecting general abnormalities and specific diagnoses (anterior cruciate ligament [ACL] tears and meniscal tears) on knee MRI exams. We then measured the effect of providing the model's predictions to clinical experts during interpretation.Methods and findingsOur dataset consisted of 1,370 knee MRI exams performed at Stanford University Medical Center between January 1, 2001, and December 31, 2012 (mean age 38.0 years; 569 [41.5%] female patients). The majority vote of 3 musculoskeletal radiologists established reference standard labels on an internal validation set of 120 exams. We developed MRNet, a convolutional neural network for classifying MRI series and combined predictions from 3 series per exam using logistic regression. In detecting abnormalities, ACL tears, and meniscal tears, this model achieved area under the receiver operating characteristic curve (AUC) values of 0.937 (95% CI 0.895, 0.980), 0.965 (95% CI 0.938, 0.993), and 0.847 (95% CI 0.780, 0.914), respectively, on the internal validation set. We also obtained a public dataset of 917 exams with sagittal T1-weighted series and labels for ACL injury from Clinical Hospital Centre Rijeka, Croatia. On the external validation set of 183 exams, the MRNet trained on Stanford sagittal T2-weighted series achieved an AUC of 0.824 (95% CI 0.757, 0.892) in the detection of ACL injuries with no additional training, while an MRNet trained on the rest of the external data achieved an AUC of 0.911 (95% CI 0.864, 0.958). We additionally measured the specificity, sensitivity, and accuracy of 9 clinical experts (7 board-certified general radiologists and 2 orthopedic surgeons) on the internal validation set both with and without model assistance. Using a 2-sided Pearson's chi-squared test with adjustment for multiple comparisons, we found no significant differences between the performance of the model and that of unassisted general radiologists in detecting abnormalities. General radiologists achieved significantly higher sensitivity in detecting ACL tears (p-value = 0.002; q-value = 0.019) and significantly higher specificity in detecting meniscal tears (p-value = 0.003; q-value = 0.019). Using a 1-tailed t test on the change in performance metrics, we found that providing model predictions significantly increased clinical experts' specificity in identifying ACL tears (p-value < 0.001; q-value = 0.006). The primary limitations of our study include lack of surgical ground truth and the small size of the panel of clinical experts.ConclusionsOur deep learning model can rapidly generate accurate clinical pathology classifications of knee MRI exams from both internal and external datasets. Moreover, our results support the assertion that deep learning models can improve the performance of clinical experts during medical imaging interpretation. Further research is needed to validate the model prospectively and to determine its utility in the clinical setting.

Introduction Mortality rates are higher in disadvantaged communities. However, accurate quantification of inequalities in Australia has been limited by data availability. The Australian Bureau of Statistics has recently created a resource linking Death Registrations to Australian Census data, enabling quantification of mortality by whole-of-population individual-level measures. Objectives and Approach We present the first analysis of linked Deaths Registrations to Census data, which quantifies mortality inequality in Australia in relation to individual-level socioeconomic position (SEP), and compares these estimates to those based on area-level-SEP measures. The Deaths Registrations-Census file contains deaths within 13 months of the 2011 Census date, linked probabilistically to 2011 Census data. We used Poisson regression to quantify inequalities according to education, weighted to adjust for relative under- and over-representation of selected subpopulations. We compared these inequality estimates with those based on area-SEP measures. We also examined the effect of missing Census data. Results Mortality rates decreased with education in all age groups (25-44, 45-64, 65-84, 85+ years), for both males and females. Estimates of relative inequality decreased with age, while estimates of absolute inequalities increased. Total excess deaths associated with lower education were highest in those aged 64-84 years. Inequality estimates for education were higher than those for area-SEP in the youngest age groups (25-45 years), but were lower in the 45-64 age group. Socioeconomic gradients in education remained apparent among individuals within each area-SEP quintile, highlighting the socioeconomic variation among individuals within these area-based socioeconomic groups. The proportion of deaths with missing education data increased with age and area-level SEP; however there was little difference in the area-based inequality estimates across subgroups with and without education missing. Conclusion/Implications The newly-created linked Deaths Registrations-Census file, accessible through the virtual ABS Datalab, is a rich resource for generating evidence on mortality. The data show mortality inequalities in education across all age groups and within quintiles of area-level SEP and indicate area-based measures are inadequate for fully capturing inequality.

Using a GARCH model the paper sought to test the hypothesis that price volatility of key Sub Saharan Africa primary commodity exports, have not changed over the past four decades. Whilst crude oil, aluminium, cocoa and six others have not experienced significant change in price volatility over the period, nine other major commodities recorded changes. Efforts need to be made to extensively diversify the portfolio of agricultural commodity exports by including new products of which price volatilities in the past decades have been reduced. This is crucial for countries that depend on up to three primary commodities for the bulk of their foreign exchange earnings. Other measures such as value addition can also help in reducing impacts of unfavourable price movements.

This study aims to investigate the extent to which the Indonesian corporate governance mechanism acts as an effective tool for protecting financial statements users against accounting irregularities. Considering that accounting irregularities might occur in between error and the fraud act, this study reviews the literature on minimizing the seriousness of these reporting incidences. The level of seriousness in misstatements is more severe when: (1) there is absence of financial expert(s) on supervisory boards and audit committees, (2) companies have short tenured-CEOs and poor internal control systems, and (3) auditors are solely appointed by firms’ BOCs without agreement of block holders (known as referral). In addition, an examination of simultaneous effects of each corporate governance dimension reveals a general weakness of the BOCs and their audit committees. However, the BOC and audit committee could be an effective tool in mitigating reporting incidences, especially when they show high-quality collaboration.

The paper sought to examine the impact of instability in primary commodity export earnings and the level of commodity dependence on economic growth in Sub Saharan Africa (SSA). Fixed effects panel data estimator was used in the empirical estimation. The findings of the study suggest that there is a negative relationship between instability in export earnings and economic growth. The results also indicate that the level of commodity dependence matter in determining economic growth in the region. The results of the paper have economic development policy implications for SSA economies and these are not farfetched. First, it appears the difficult growth experience of SSA is not solely due to instability in export receipts. The question of continued dependence on a narrow range of primary commodities is also matter of great importance.

Targeted Induced Local Lesions in Genomes (TILLING) is a reverse genetics approach to identify novel sequence variation in genomes, with the aims of investigating gene function and/or developing useful alleles for breeding. Despite recent advances in wheat genomics, most current TILLING methods are low to medium in throughput, being based on PCR amplification of the target genes. We performed a pilot-scale evaluation of TILLING in wheat by next-generation sequencing through exon capture. An oligonucleotide-based enrichment array covering ~2 Mbp of wheat coding sequence was used to carry out exon capture and sequencing on three mutagenised lines of wheat containing previously-identified mutations in the TaGA20ox1 homoeologous genes. After testing different mapping algorithms and settings, candidate SNPs were identified by mapping to the IWGSC wheat Chromosome Survey Sequences. Where sequence data for all three homoeologues were found in the reference, mutant calls were unambiguous; however, where the reference lacked one or two of the homoeologues, captured reads from these genes were mis-mapped to other homoeologues, resulting either in dilution of the variant allele frequency or assignment of mutations to the wrong homoeologue. Competitive PCR assays were used to validate the putative SNPs and estimate cut-off levels for SNP filtering. At least 464 high-confidence SNPs were detected across the three mutagenized lines, including the three known alleles in TaGA20ox1, indicating a mutation rate of ~35 SNPs per Mb, similar to that estimated by PCR-based TILLING. This demonstrates the feasibility of using exon capture for genome re-sequencing as a method of mutation detection in polyploid wheat, but accurate mutation calling will require an improved genomic reference with more comprehensive coverage of homoeologues.

Retinyl esters represent an insoluble storage form of vitamin A and are substrates for the retinoid isomerase (Rpe65) in cells of the retinal pigment epithelium (RPE). The major retinyl-ester synthase in RPE cells is lecithin:retinol acyl-transferase (LRAT). A second palmitoyl coenzyme A-dependent retinyl-ester synthase activity has been observed in RPE homogenates but the protein responsible has not been identified. Here we show that diacylglycerol O-acyltransferase-1 (DGAT1) is expressed in multiple cells of the retina including RPE and Müller glial cells. DGAT1 catalyzes the synthesis of retinyl esters from multiple retinol isomers with similar catalytic efficiencies. Loss of DGAT1 in dgat1(-/-) mice has no effect on retinal anatomy or the ultrastructure of photoreceptor outer-segments (OS) and RPE cells. Levels of visual chromophore in dgat1(-/-) mice were also normal. However, the normal build-up of all-trans-retinyl esters (all-trans-RE's) in the RPE during the first hour after a deep photobleach of visual pigments in the retina was not seen in dgat1(-/-) mice. Further, total retinyl-ester synthase activity was reduced in both dgat1(-/-) retina and RPE.

BackgroundA promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat.Methodology/principal findingsAnimals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed.Conclusions/significanceWild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo.

International literature clearly demonstrates the potential for gender-based inequalities to constrain development processes. In the United Nations Development Programme Gender-related Development Index, Australia ranks in the top five across 177 countries, suggesting that the loss of human development due to gender inequality is minor. However, such analysis has not been systematically applied to the Indigenous Australian population, at least in a quantitative sense. Using the 2006 Australian Census, this paper provides an analysis across three dimensions of socioeconomic disparity: Indigeneity, gender, and geography. This paper also explores the development of a similar gender-related index as a tool to enable a relative ranking of the performance of Indigenous males and females at the regional level across a set of socioeconomic outcomes.The initial findings suggest that although there is a substantial development gap between Indigenous and non-Indigenous Australians, the development loss from gender-related inequality for Indigenous Australians is relatively small. Higher life expectancy and education attainment for Indigenous females balances out their slightly lower earnings to a large extent. At the regional level, Indigenous females tend to fare better than Indigenous males for the set of indicators chosen; and, this is particularly true in capital cities.

Objectives: During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity., Methods: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study., Results: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95., Conclusions: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)