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Intimate Partner Violence (IPV) is a risk factor for depressive disorders and other harms to women and their pregnancy. There is a need for longitudinal evidence to assist with understanding the subgroups of women including those from refugee background affected by IPV. We recruited women at their prenatal visit from three antenatal clinics in Australia (January 2015–March 2016). A total of 1335 women, 650 (48.7%) born in Australia and 685 (51.3%) from refugee backgrounds, completed baseline assessment; then, Time 2 follow-up was at 6 months and Time 3 follow-up was at 24 months post birth. The WHO Intimate Partner Violence (IPV) measure was used. Latent class growth analysis grouped individuals based on trajectories of IPV across three time points. A three-step process identified characteristics associated with respective latent class membership. Similar three-class solutions were observed across both cohorts, composed of Limited IPV (64% and 48% Australian-born and refugee background, respectively); Changing IPV (31%; 46%)—various combinations of IPV categories across time; Combined IPV (4%; 6%)—IPV at all time points, all transitioning to the combined physical and psychological abuse category at Time 3. Older age, fewer children, being in a couple, having a better partner, family and friend relationships, fewer partner trauma events, and fewer living difficulties emerged as protective factors for the changing and combined categories, with a distinct pattern for the refugee cohort. The findings assist with understanding and defining of the highest risk group for targeting interventions to prevent IPV, and the unique protective factors across the two IPV-affected classes for women born in Australia and those who arrived as refugees.

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.

In der Forschung zur elterlichen Medienerziehung besteht weitestgehend Konsens über die Relevanz bestimmter Strategien wie einer aktiven Begleitung und dem Setzen von Regeln. Trotz umfangreicher Forschung gibt es jedoch nur wenige standardisierte Messinstrumente, die dabei zwischen einer interaktiven und einer nicht-interaktiven Mediennutzung der Kinder unterscheiden. Diese Differenzierung wurde von Nimrod, Elias und Lemish (2019a) aufgegriffen und in einer Untersuchung mit Grosseltern empirisch überprüft. In der vorliegenden Studie wurde die dafür entwickelte Skala anhand einer Befragung von 1.330 Müttern in Deutschland mit Kindern zwischen zwei und 14 Jahren adaptiert und validiert. Die Ergebnisse bestätigen eine gute Passung der Skala für Mütter jüngerer Kinder (zwei bis sieben Jahre). Demnach ist es gerade für diese Zielgruppe relevant, die elterliche Medienerziehung zumindest mit Blick auf bestimmte Strategien (insbesondere restrictive mediation, supervision) stärker nach den medialen Aktivitäten des Kindes zu differenzieren. Mit steigendem Alter des Kindes scheint eine entsprechende Differenzierung dagegen zunehmend obsolet zu werden.

Abstract Background Local humanitarian workers in low and middle-income countries must often contend with potentially morally injurious situations, often with limited resources. This creates barriers to providing sustainable mental health and psychosocial support (MHPSS) to displaced individuals. Clinical supervision is an often neglected part of ensuring high-quality, sustainable care. The Caring for Carers (C4C) project aims to test the effectiveness and acceptability of online group-based supportive supervision on the well-being of MHPSS practitioners, as well as service-user-reported service satisfaction and quality when working with displaced communities in Türkiye, Syria, and Bangladesh. This protocol paper describes the aim, design, and methodology of the C4C project. Method A quasi-experimental, mixed-method, community-based participatory research study will be conducted to test the effectiveness of online group-based supportive clinical supervision provided to 50 Syrian and 50 Bangladeshi MHPSS practitioners working with Syrian and Rohingya displaced communities. Monthly data will be collected from the practitioners and their beneficiaries during the active control (six months) and supervision period (16 months over two terms). Outcomes are psychological distress (Kessler-6), burnout (the Copenhagen Burnout Inventory), compassion fatigue, compassion satisfaction, and secondary traumatic stress (Professional Quality of Life Scale), perceived injustice, clinical self-efficacy (Counseling Activity Self-Efficacy Scale), service satisfaction, and quality (Client Satisfaction Questionnaire and an 18-item measure developed in this project). A realist evaluation framework will be used to elucidate the contextual factors, mechanisms, and outcomes of the supervision intervention. Discussion There is a scarcity of evidence on the role of clinical supervision in improving the well-being of MHPSS practitioners and the quality of service they provide to displaced people. By combining qualitative and quantitative data collection, the C4C project will address the long-standing question of the effectiveness and acceptability of clinical supervision in humanitarian settings.

Membrane lipid composition is critical for an organism’s growth, adaptation, and functionality. Mosses, as early non-vascular land colonizers, show significant adaptations and changes, but their dynamic membrane lipid alterations remain unexplored. Here, we investigated the temporal changes in membrane lipid composition of the moss Physcomitrium patens during five developmental stages and analyzed the acyl content and composition of the lipids. We observed a gradual decrease in total lipid content from the filamentous protonema stage to the reproductive sporophytes. Notably, we found significant levels of very long-chain polyunsaturated fatty acids, particularly arachidonic acid (C20:4), which are not reported in vascular plants and may aid mosses in cold and abiotic stress adaptation. During vegetative stages, we noted high levels of galactolipids, especially monogalactosyldiacylglycerol, associated with chloroplast biogenesis. In contrast, sporophytes displayed reduced galactolipids and elevated phosphatidylcholine and phosphatidic acid, which are linked to membrane integrity and environmental stress protection. Additionally, we observed a gradual decline in the average double bond index across all lipid classes from the protonema stage to the gametophyte stage. Overall, our findings highlight the dynamic nature of membrane lipid composition during moss development, which might contribute to its adaptation to diverse growth conditions, reproductive processes, and environmental challenges.

Abstract Background Hip fracture creates a major burden on society due to high mortality, loss of independence and excess medical costs for older people. A multidisciplinary co-managed model of care is widely considered as the best practice for the management of older patients with hip fracture. The study aims to develop a conceptual framework to inform the future scale-up of this model of care through the identification of barriers and enablers that may influence successful uptake. Methods This qualitative study was conducted within an interventional study, which aimed to test the effectiveness of co-managed model of care for older patients with hip fracture. Health providers and health administrators from three hospitals were purposively selected and interviewed in-depth. The Consolidated Framework for Implementation Research (CFIR) was used to develop interview guides, collect and analyse data. Inductive and deductive approaches were used to generate enablers or barriers, aligned with the CFIR constructs. All barriers or enablers were inductively summarised to a conceptual framework with essential components to guide the implementation of co-managed model of care in other hospitals. Results A total of 13 health providers and 3 health administrators were recruited. The main barriers to co-managed care implementation included perceived complexity of implementation, insufficient international collaboration and incentives, the absence of national guideline support and lack of digital health applications for communication between health providers, insufficient number of health providers and beds, and poor understanding about the effectiveness of this care model. A conceptual framework for future scale-up was then developed, consisting of the following essential components: hospital authority support, enabling environment, adequate number of beds, sufficient and skilled health providers, use of digital health technology, regular quality supervision, evaluation and feedback, and external collaborations. Conclusions Despite the complexity of the intervention, the co-managed model of care has the potential to be implemented and promoted in China and in similar settings, although there is a need to demonstrate feasibility in different settings.

This study estimated the effects of the COVID-19 pandemic on maternal mortality in Chile between 2020 and 2021. A natural experiment was conducted using official data on maternal deaths and live births (LBs) between 1997 and 2021. The effects of the SARS-CoV-2 outbreak were evaluated using interrupted time series (ITS) and an autoregressive integrated moving average (ARIMA) model to forecast the expected rates on MMR and 95% confidence intervals (95% CI). In Chile, following World Health Organization suggestions, maternal deaths aggravated by SARS-CoV-2 are assigned to code O98.5 (non-respiratory infectious indirect) accompanied by code U07.1 or U07.2, depending on confirmation of the presence or absence of the virus. ITS analysis revealed that the SARS-CoV-2 outbreak impacted the MMR due to indirect causes, with a greater increase in indirect nonrespiratory causes than respiratory causes. The ARIMA forecast was consistent with ITS, showing that the expected MMR for indirect causes (3.44 in 2020 and 1.55 in 2021) was substantially lower than the observed rates (9.65 in 2020 and 7.46/100.000 LBs in 2021). For nonrespiratory indirect causes, the observed values of the MMR for 2020 (8.77/100.000 LBs) and 2021 (7.46/100.000 LBs) were double the predicted values of 4.02 (95% CI: 0.44-7.61) and 3.83 (95% CI: -0.12-7.79), respectively. A lower effect was observed on direct obstetrical deaths. During 2020-2021, there was a rise in the MMR in Chile attributable to SARS-CoV-2. The pandemic contributed to an escalation in the MMR due to indirect causes, particularly nonrespiratory and infectious causes. MMR due to direct obstetric causes were less affected. This suggests that the pandemic disproportionately affected maternal health by exacerbating conditions unrelated to pregnancy, childbirth, or postpartum, more than those directly linked to obstetric complications.

At the cellular level, membrane damage is a fundamental cause of yield loss at high temperatures (HT). We report our investigations on a subset of a peanut (Arachis hypogaea) recombinant inbred line population, demonstrating that the membrane lipid remodeling occurring at HT is consistent with homeoviscous adaptation to maintain membrane fluidity. A major alteration in the leaf lipidome at HT was the reduction in the unsaturation levels, primarily through reductions of 18:3 fatty acid chains, of the plastidic and extra-plastidic diacyl membrane lipids. In contrast, levels of 18:3-containing triacylglycerols (TGs) increased at HT, consistent with a role for TGs in sequestering fatty acids when membrane lipids undergo remodeling during plant stress. Polyunsaturated acyl chains from membrane diacyl lipids were also sequestered as sterol esters (SEs). The removal of 18:3 chains from the membrane lipids decreased the availability of susceptible molecules for oxidation, thereby minimizing oxidative damage in membranes. Our results suggest that transferring 18:3 chains from membrane diacyl lipids to TGs and SEs is a key feature of lipid remodeling for HT adaptation in peanut. Finally, QTL-seq allowed the identification of a genomic region associated with heat-adaptive lipid remodeling, which would be useful for identifying molecular markers for heat tolerance.

When being online, young users are often confronted with insulting, hateful, or misleading messages. To handle these dark forms of participation, it is essential to equip them with resources that support their social literacy in today’s complex online environments. In the present article, we deployed a previously established scale on self-perceived participatory-moral literacy and conducted a broad online survey study with 1,489 adolescents and young adults aged 16–22 years ( M = 19.74; SD = 1.65; 51% female) across eight different European countries (Austria, France, Germany, Hungary, Italy, Poland, Slovakia, and the United Kingdom). The results provided a configural identical model of participatory-moral abilities, motivation, and behavior across the considered European countries. We could confirm weak invariance, satisfactory psychometric qualities, and convergent validity of the scale across the different countries. Implications for digital literacy research are discussed.

Background: Impairments in executive functioning associated with posttraumatic stress disorder (PTSD) may impact the capacity of refugees and asylum seekers. Aims: To examine the association between executive functioning and PTSD with and without prominent future-focused threat (FFT) intrusions at rest and after threat priming. Method: 66 Farsi and Dari-speaking asylum-seekers, refugees, and immigrants were recruited into 3 groups: High PTSD & FFT Symptoms; High PTS Symptoms; Low PTSD & FFT symptoms. The Category Fluency Test (animals; food; flora) in Farsi was administered at baseline and after two counter-balanced future- and past-focused threat narrative tasks. Results: Higher PTSD and FFT symptom scores was associated with reduced verbal fluency [correct words (PTS p

Smartphones are omnipresent in the daily lives of parents and provide access to multiple resources in stressful situations. Thus, smartphones might be valuable coping tools. Previous research has mostly focused on the negative effects of parental phone use. In the present study, we investigated how mothers use smartphones for coping with stress and whether their phone use for coping is effective. We also explored factors on different levels (situation, person, device) which could influence phone use and coping effectiveness. Building on a one-week experience sampling study with over 200 mothers and multilevel models, we found that in stressful situations while being with children, mothers used their smartphones mostly for emotion-focused coping such as self-distraction and taking a break. Problem-focused coping was less prevalent. Mothers reporting increased cognitive phone salience used it more for coping with stress. Phone use for coping compared to no use related to lower stress decrease. No person-, situation-, or device-specific factors moderated the effects of phone use on coping effectiveness. Using positive phone content, however, was associated with increased perceived coping efficacy. Our results suggest that phone use is not generally successful for coping, but that momentary device-specific factors such as content characteristics might determine whether phones can be used for coping in an effective way.

Evidence suggests that inhibition of α/β hydrolase-domain containing 6 (ABHD6) reduces seizures; however, the molecular mechanism of this therapeutic response remains unknown. We discovered that heterozygous expression of Abhd6 (Abhd6+/−) significantly reduced the premature lethality of Scn1a+/− mouse pups, a genetic mouse model of Dravet Syndrome (DS). Both Abhd6+/− mutation and pharmacological inhibition of ABHD6 reduced the duration and incidence of thermally induced seizures in Scn1a+/− pups. Mechanistically, the in vivo anti-seizure response resulting from ABHD6 inhibition is mediated by potentiation of gamma-aminobutyric acid receptors Type-A (GABAAR). Brain slice electrophysiology showed that blocking ABHD6 potentiates extrasynaptic (tonic) GABAAR currents that reduce dentate granule cell excitatory output without affecting synaptic (phasic) GABAAR currents. Our results unravel an unexpected mechanistic link between ABHD6 activity and extrasynaptic GABAAR currents that controls hippocampal hyperexcitability in a genetic mouse model of DS. Brief summary: This study provides the first evidence for a mechanistic link between ABHD6 activity and the control of extrasynaptic GABAAR currents that controls hippocampal hyperexcitability in a genetic mouse model of Dravet Syndrome and can be targeted to dampened seizures.

Orientation: The coronavirus disease 2019 (COVID-19) pandemic negatively affected borrowers’ ability to repay debt, which is expected to influence banks’ calculation of their expected credit loss (ECL) allowance. Comprehensive disclosure regarding the application of managerial judgement in calculating ECLs would produce decision-useful financial information. Research purpose: This study explored the effects of the COVID-19 pandemic on the measurement and disclosure of ECL allowances by South African listed banks. Motivation for the study: It is unknown whether decision-useful financial information regarding South African banks’ ECLs was produced during the pandemic, mirroring developed countries. Research approach/design and method: Content analysis of quantitative and qualitative data from annual financial statements was employed for a sample of listed banks. Main findings: Banks employed a variety of relief measures to accommodate borrowers, but these relief measures did not automatically trigger a significant increase in credit risk. More loans were subject to lifetime ECLs, causing the ECL allowance to increase substantially during the first year of the pandemic. Forward-looking information as well as postmodel adjustments were employed to measure the ECL allowance. Practical/managerial implications: The ECL allowances of South African listed banks increased during the pandemic. Disclosure in the annual financial statements and identifying ECLs as a key audit matter provided evidence of adequate consideration of the credit risk and forward-looking information influencing ECLs by banks and their auditors. Improved disclosure regarding postmodel adjustments is required. Contribution/value-add: During the COVID-19 pandemic, decision-useful financial information regarding the calculation of banks’ ECL allowances was available for South African banks, mirroring developed countries.

Objective Emergency service workers are at risk of experiencing poor mental health due to repeated exposure to potentially traumatic events. Promoting healthy lifestyle factors may help improve health outcomes and quality of life among this population. This study aimed to evaluate the efficacy of a 10-week physical activity (PA) and diet programme delivered via Facebook for sedentary emergency service workers and their support partners on levels of psychological distress. Methods We delivered a 10-week intervention via a private Facebook group facilitated by exercise physiologists, a dietitian and peer-facilitators. Weekly education modules and telehealth calls were delivered, and participants were provided with a PA tracking device (Fitbit accelerometer). A stepped-wedge design was applied to compare levels of psychological distress (K6) during baseline, to intervention by comparing slopes of change. Secondary pre–post outcomes included mental health symptoms, PA, quality of life, social support to exercise, sleep quality and suicidal ideation. Results In total, N =90 participants ( n =47 emergency service workers and n =43 support partners) were recruited in 4 cohorts (aged 42.3±11.5 years, 51% male). Levels of psychological distress did not change significantly during the baseline (control) slope and reduced significantly during the first 6 weeks of intervention (intervention slope 1). The slopes were significantly different, b =−0.351, p = 0.003 (i.e. the trajectories of change) and improvements plateaued until follow up. Retention was high (92%) and improvements in mental health symptoms, minutes of PA, sedentary time and quality of life were significant. Conclusions Our intervention delivered via social media is feasible and associated with reduced levels of psychological distress among emergency service workers and support partners. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN): 12619000877189.

Intimate Partner Violence (IPV) is a major public health issue, including during pregnancy where it poses a serious risk to the woman’s health. Influenza-Like Illness (ILI) also causes significant morbidity for women during pregnancy. It may be possible that ILI in pregnancy is associated with IPV, and that depression and trauma history play a role in the connection. 524 Australia-born women and 578 refugee-background women participated in the study. Baseline participants were randomly recruited and interviewed from antenatal clinics between January 2015 and March 2016, and they were reinterviewed six months post-partum. Bivariate and path analysis were used to assess links between IPV, depression and ILI. One in 10 women (10%; 111 out of 1102) reported ILI during their pregnancy period and this rate was significantly (p < 0.001) higher for women born in conflict-affected countries (13%; 76 out of 578) as compared to Australian-born women (7%; 35 out of 524). In both groups, Time 1 traumatic events, IPV and depression symptoms were significantly associated with ILI at Time 2. A significant association between IPV at Time 1 and ILI at Time 2 was fully mediated by depression symptoms at Time 1 (Beta = 0.36 p < 0.001). A significant direct path was shown from depression symptoms to ILI (Beta = 0.26, p < 0.001). Regardless of migration history, pregnant women who have experienced IPV and depression are more likely to report influenza-like symptoms in pregnancy. This may suggest that trauma and depression negatively affect immunity, although it could also indicate a connection between depressive symptoms and physical experiences of ILI.

Summary: Background: This research examined the mental health of a cohort of asylum-seeking children, adolescents and their primary caregiver affected by insecure residency while living in the community, compared to refugees and immigrants. Methods: The project investigated the prevalence of psychosocial problems among Iranian and Afghani asylum seeker, refugee and immigrant children and adolescents, and their caregivers who arrived in Australia from 2010. In total, n=196 children and adolescents aged 5–18 years, and their primary caregiver were asked about family visa status, country of origin, level of education, parent symptoms of posttraumatic stress disorder (Harvard Trauma Questionnaire) and child wellbeing (Strengths and Difficulties Questionnaire). An additional n=362 Farsi and Dari speaking children, recruited through the Building a New Life in Australia (BNLA) study, a national comparison sample of families with permanent refugee visas, were included. Findings: Asylum seeker children and adolescents displayed significantly more psychosocial problems compared to those with full refugee protection and immigrant background within the current sample and when benchmarked against a national sample of Farsi-Dari speaking refugee children. Higher parental posttraumatic stress disorder symptoms was associated with poorer child and adolescent psychosocial functioning. This effect was more marked in families with insecure residency. Interpretation: Insecure visa status is associated with higher rates of children's mental health problems and a stronger association with parental PTSD symptoms compared to children with secure residency. This raises important questions about Australia's restrictive immigration policies. Funding: This project was supported by an Australian Rotary Health Research Fund / Mental Health of Young Australians Research Grant and by the Australian Research Council (DP160104378).

Diese Woche, am 26. und 27. Juli verhandelte das Bundesverfassungsgericht das „Eigenmittelbeschluss-Ratifizierungsgesetz“ (ERatG). Die politischen Entscheidungen, die in Gestalt des Wiederaufbaufonds „Next Generation EU“ in rechtliche Form gegossen wurden, trafen dabei auf alte Rechtsfragen.

Abstract Background Rare diseases may be defined as occurring in less than 1 in 2000 patients. Such conditions are, however, so numerous that up to 5.9% of the population is afflicted by a rare disease. The gambling industry attests that few people have native skill evaluating probabilities. We believe that both students and academics, under-estimate the likelihood of encountering rare diseases. This combines with pressure on curriculum time, to reduce both student interest in studying rare diseases, and academic content preparing students for clinical practice. Underestimation of rare diseases, may also contribute to unhelpful blindness to considering such conditions in the clinic. Methods We first developed a computer simulation, modelling the number of cases of increasingly rare conditions encountered by a cohort of clinicians. The simulation captured results for each year of practice, and for each clinician throughout the entirety of their careers. Four hundred sixty-two theoretical conditions were considered, with prevalence ranging from 1 per million people through to 64.1% of the population. We then delivered a class with two in-class on-line surveys evaluating student perception of the importance of learning about rare diseases, one before and the other after an in-class real-time computer simulation. Key simulation variables were drawn from the student group, to help students project themselves into the simulation. Results The in-class computer simulation revealed that all graduating clinicians from that class would frequently encounter rare conditions. Comparison of results of the in-class survey conducted before and after the computer simulation, revealed a significant increase in the perceived importance of learning about rare diseases (p

Domestic abuse perpetration remains a major threat to public health, safety and wellbeing, causing serious harms and contributing significantly to overall crime globally. In the United Kingdom, research links the crime type to high economic and social costs. In the last 10 years, our collective knowledge of domestic abuse has grown in conjunction with its prioritisation in government policy. Several innovative studies have built a picture of the most serious cases and overall patterns of abuse but to date, examination of these trends by ethnic groups has been limited despite increasing attention to disproportionality in racially minoritised communities in criminal justice system outcomes. In this article we aimed to address this issue through the analysis of 150,000 domestic abuse records kept by police forces in England. Using descriptive statistics, we examined the relative distributions of different ethnicities by suspected offending rate, investigative outcome and crime harm. We found two patterns of note: firstly, that suspects from several categories of minoritized communities are consistently over-represented compared to the White British population among most harmful cases, and secondly, that in Asian communities, offences are less frequently “solved.” We discuss the implications for future research and practice.

Objectives: The COVID-19 pandemic has disrupted health care for non-communicable diseases (NCDs) and necessitated strategies to minimize contact with facilities. We aimed to examine factors influencing implementation of remote (non-facility-based) delivery approaches for people with hypertension and/or diabetes in low- and middle-income countries (LMICs), to inform NCD care delivery during health service disruption, including humanitarian crises.Methods: Our narrative review used a hermeneutic and purposive approach, including primary studies conducted in LMICs, which assessed implementation factors influencing remote NCD care delivery. Results were analyzed using the Consolidated Framework for Implementation Research.Results: Twenty-eight included studies revealed the strong influence of both internal organizational and broader contextual factors, such as community health worker policies or technological environment. Addressing patients’ specific characteristics, needs and resources was important for implementation success.Conclusion: This review highlighted the multiple, complex, interdependent factors influencing implementation of remote NCD care in LMICs. Our findings may inform actors designing NCD care delivery in contexts where facility-based access is challenging. Implementation research is needed to evaluate context-adapted e-Health, community-based, and simplified clinical management strategies to facilitate remote NCD care.

Abstract Magnetic Resonance Imaging (MRI) is well‐suited for imaging peripheral blood flow due to its non‐invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI‐based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric‐adolescent population using phase contrast MRI, and to present test‐retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC‐MRI of the femoral artery at rest and following a 5 × 30 s of in‐magnet exercise. To evaluate test‐retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest‐peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest‐peak ICC = 0.87, p = 0.003) between‐visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV’s) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest‐peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non‐invasive phase contrast MRI. The MRI‐based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test‐retest reliability both at rest and immediately post‐exercise.

Abstract Understanding the changes in peanut (Arachis hypogaea L.) anther lipidome under heat stress (HT) will aid in understanding the mechanisms of heat tolerance. We profiled the anther lipidome of seven genotypes exposed to ambient temperature (AT) or HT during flowering. Under AT and HT, the lipidome was dominated by phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TAG) species (> 50% of total lipids). Of 89 lipid analytes specified by total acyl carbons:total carbon–carbon double bonds, 36:6, 36:5, and 34:3 PC and 34:3 PE (all contain 18:3 fatty acid and decreased under HT) were the most important lipids that differentiated HT from AT. Heat stress caused decreases in unsaturation indices of membrane lipids, primarily due to decreases in highly-unsaturated lipid species that contained 18:3 fatty acids. In parallel, the expression of Fatty Acid Desaturase 3-2 (FAD3-2; converts 18:2 fatty acids to 18:3) decreased under HT for the heat-tolerant genotype SPT 06-07 but not for the susceptible genotype Bailey. Our results suggested that decreasing lipid unsaturation levels by lowering 18:3 fatty-acid amount through reducing FAD3 expression is likely an acclimation mechanism to heat stress in peanut. Thus, genotypes that are more efficient in doing so will be relatively more tolerant to HT.

Objective To describe the pharmacists’ workflow, including tasks and time spent, to better understand their work capacity.Design Cross-sectional, observational, time and motion study.Setting Community pharmacies in Western Australia and New South Wales, Australia.Participants Currently registered and practising pharmacists were approached using snowball sampling and selected using purposive techniques to obtain balance representation of metropolitan and rural pharmacies, as well as high and low script volumes where possible.Results Twenty-four pharmacists across 15 pharmacies participated during the 135 sessions totalling over 274 hours of observation. Dispensing (30%), indirect patient services (17%), counselling (15%) and professional management activities (15%) were the top four duties pharmacists performed, while only 2% of time was spent on professional services such as pain clinics and influenza vaccinations. Tasks were frequently interrupted and often performed simultaneously. Breaks and consumer-contact times were limited. More time was spent on professional service activities in non-metropolitan pharmacies, in pharmacies with greater daily prescription volumes and those with one or more support pharmacists.Conclusions This is the first study to quantify the pharmacists’ tasks in Australian community pharmacies. Much time is being spent on dispensing, supply and management activities with little time for providing additional professional services. An extra supporting pharmacist is likely necessary to increase professional services. These findings could support future research around barriers and enablers of conducive workflows and of extended professional services.

Background: Emerging pandemic viruses may have multiple deleterious effects on maternal health. This study examines the effects of a pandemic influenza virus on cause-specific maternal mortality time series, using Argentinian vital statistics. Methods: We conducted a population-based natural experiment from national vital records of maternal deaths between 1980 and 2017. Joinpoint regression models were used to model time series of the maternal mortality ratio (MMR). The sensitivity of the registry to detect the effects of the pandemic H1N1 2009 influenza virus on cause-specific MMR was analysed using a panel of parallel interrupted time series (ITS). Findings: Over this 38-year study, the MMR decreased by 58·6% (69·5 to 28·8 deaths/100,000 live births), transitioning from direct obstetric causes (67·0 to 21·1/100,000 live births; 68·4% decrease) to indirect causes (2·6 to 7·7/100,000 live births; 196·2% increase). The regression analysis showed an average reduction of -2·2%/year (95% CI: -2·9 to -1·4) with 2 join points in the total trend (1998 and 2009). Parallel ITS analyses revealed the pandemic H1N1 virus had an increasing effect on mortality from the respiratory system- and sepsis-related complications (level change 4·7 and 1·6/100,000 live births respectively), reversing after the outbreak. No effect was found on MMR from hypertensive disorders, haemorrhage, abortive outcomes, other direct obstetric causes, and indirect non-respiratory comorbidities. Interpretation: The Argentinian maternal death registry appears sensitive to detect different effects of emerging infectious epidemics on maternal health. In a population-based natural experiment, pandemic H1N1 virus impacted maternal mortality almost exclusively from the respiratory system- and sepsis-related complications. Funding: Supported by FISAR www.fisarchile.org

Patients with relapsed and/or refractory multiple myeloma (RRMM) generally have limited treatment options and a poor prognosis. Previous trials demonstrated that pomalidomide combined with low-dose dexamethasone (Pd) is effective in these patients with significant responses and improved progression-free survival (PFS). Pd has been approved in RRMM patients who received ≥2 prior lines of therapy. Here, we present the results of a population-based study of patients with RRMM treated with Pd in The Netherlands from time of pomalidomide approval. Using the nationwide Netherlands Cancer Registry, data from all nontrial patients with RRMM treated with Pd were collected. Data were analyzed of response, PFS, and overall survival (OS). A total of 237 patients were included in this analysis. Previous treatment consisted of a proteasome inhibitor in 227 patients (96%) and/or an immune-modulating agent in 235 patients (99%). One hundred forty patients (59%) were refractory to an immune-modulating agent in their last line of therapy. Median time from diagnosis to treatment with Pd was 4.9 years (interquartile range, 2.7–7.9), and the median number of prior treatments was 4 (interquartile range, 3–5). Median PFS and OS for all patients were 3.6 months (95% confidence interval [CI], 3.1–3.8) and 7.7 months (95% CI, 5.7–9.7), respectively. For patients achieving ≥PR, median PFS and OS were 10.6 months (95% CI, 8.3–12.9) and 16.3 months (95% CI, 13.6–23.2), respectively. This nationwide, population-based registry study confirms data shown in pivotal clinical trials on Pd. PFS in this analysis is comparable to PFS observed in those clinical trials.

Objective: The World Health Organization (WHO) included single-pill combination (SPC) antihypertensive medications on their 2019 essential medicines list (EML) to encourage uptake and improved hypertension control. We documented key national-level facilitators (SPCs on national EMLs, recommendation for SPCs in national hypertension guidelines and availability of SPCs on the market) supporting uptake of SPCs in the 30 most populous low- and middle-income countries (LMICs). Methods: A hierarchical information gathering strategy was used including literature and web searches, the use of organisational databases and personal communications with colleagues to obtain information on (1) whether SPC antihypertensives are on national EMLs, (2) whether SPC antihypertensives are recommended in national hypertension guidelines and (3) whether SPCs are available on the market. Results: Eleven of 30 LMICs had all facilitators in place being Egypt, Kenya, Nigeria, Sudan, China, the Philippines, Thailand, Iran, Argentina, Colombia and Mexico. Twenty-six countries had national hypertension guidelines (or similar) in place with SPCs being recommended in 18 of these. Apart from Afghanistan, SPCs were available on the market in all countries. The facilitator least present was the inclusion of SPC antihypertensives on national EMLs at 12 of 29 (Turkey does not have an EML). Conclusion: This study demonstrated that many LMICs have made significant progress in their uptake of SPC antihypertensives and several had included SPCs on their EMLs and guidelines prior to their inclusion on the WHO EML. Despite this progress, the uptake of SPC antihypertensives in LMICs could be improved including through their further inclusion on EMLs.

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Background: Clinical supervision in providing mental health and psychosocial support services (MHPSSs) is an ethical imperative and a key to ensuring quality of care in terms of service users’ skills enhancement, well-being, and satisfaction. However, humanitarian contexts in low-resource countries usually lack sufficient infrastructures to ensure staff have access to supervision. Against this backdrop, a pilot supervision program was introduced in Bangladesh and Syria to help MHPSS staff provide quality care. However, supervision provided by experts unfamiliar with these contexts decontextualizes the supervision process and hinders cultural relevance. The aim of this paper is to present a decolonial model of supervision called “WONDERFUL Supervision”. Methods: We provided fortnightly online supervision to a total of 32 MHPSS practitioners (seven in Bangladesh and twenty-five in Syria) working in humanitarian contexts in Bangladesh and Syria as well as their surrounding countries (such as Türkiye) between 2019 and 2021.The issues talked about were the skills needed for the practitioners to provide optimal levels of service, manage staff burnout, and present cases. Focus group discussions and reflective discussions included 19 participants, involving both practitioners and supervisors across sites. Results: Despite some notable effects, the supervision was obstructed due to being decontextualized, such as the supervisors not having adequate knowledge about the contexts and culture of beneficiaries, a perceived feeling of power imbalance, practitioners having limited access to resources (e.g., internet connection and technical support), and different time zones. This defect paves the way for a new mode of supervision, WONDERFUL, which takes into account contextual factors and other sociocultural aspects. Conclusions: WONDERFUL supervision has the potential to indigenize the concept of clinical supervision and thereby more sustainably and effectively ensure quality mental health care in resource-limited countries, especially in humanitarian contexts.

External human–machine interfaces (eHMIs) have the potential to benefit AV–pedestrian interactions. The majority of studies investigating eHMIs have used relatively simple traffic environments, i.e., a single pedestrian crossing in front of a single eHMI on a one-lane straight road. While this approach has proved to be efficient in providing an initial understanding of how pedestrians respond to eHMIs, it over-simplifies interactions which will be substantially more complex in real-life circumstances. A process is illustrated in a small-scale study (N = 10) to rank different crossing scenarios by level of complexity. Traffic scenarios were first developed for varying traffic density, visual complexity of the road scene, road geometry, weather and visibility conditions, and presence of distractions. These factors have been previously shown to increase difficulty and riskiness of the crossing task. The scenarios were then tested in a motion-based, virtual reality environment. Pedestrians’ perceived workload and objective crossing behaviour were measured as indirect indicators of the level of complexity of the crossing scenario. Sense of presence and simulator sickness were also recorded as a measure of the ecological validity of the virtual environment. The results indicated that some crossing scenarios were more taxing for pedestrians than others, such as those with road geometries where traffic approached from multiple directions. Further, the presence scores showed that the virtual environments experienced were found to be realistic. This paper concludes by proposing a “complex” environment to test eHMIs under more challenging crossing circumstances.

Several cross-sectional studies have shown that online sexual engagement (OSE) in the form of sexting or sexy self-presentation on social media is associated with an increased risk of experiencing negative consequences, such as online sexual victimization (OSV) or lower levels of psychosocial well-being. However, representative and longitudinal studies are scarce. The current study follows three research goals: (1) examining the prevalence of OSE and OSV among a random-quota sample of 1,019 German Internet users aged 14–64 years, (2) examining gender and age-related differences in OSE and OSV, and (3) examining the longitudinal relationships between OSE, OSV, and psychosocial well-being over a period of 1 year. Our results indicate that OSE and OSV are relatively widespread: 17.7% of the participants had already experienced OSV, 25.3% indicated that they had presented themselves online in a sexualized manner at least once in the past 2 months, and 22.7% showed a certain willingness to engage in sexting. We found higher rates among the younger participants. However, to a certain degree, older individuals were also affected. Male participants showed higher sexting willingness and more often presented themselves in a sexualized manner than females, whereas only small differences related to OSV were found. Concerning relationships with psychosocial well-being, our cross-sectional results showed that OSE, OSV, and mental problems are intercorrelated. Furthermore, we detected a significant long-term relationship between higher sexting willingness at time 1 and more victimization experienced 1 year later, whereas no significant longitudinal associations with lower levels of psychosocial well-being were identified.

Abstract Background Process evaluation is increasingly recognized as an important component of effective implementation research and yet, there has been surprisingly little work to understand what constitutes best practice. Researchers use different methodologies describing causal pathways and understanding barriers and facilitators to implementation of interventions in diverse contexts and settings. We report on challenges and lessons learned from undertaking process evaluation of seven hypertension intervention trials funded through the Global Alliance of Chronic Diseases (GACD). Methods Preliminary data collected from the GACD hypertension teams in 2015 were used to inform a template for data collection. Case study themes included: (1) description of the intervention, (2) objectives of the process evaluation, (3) methods including theoretical basis, (4) main findings of the study and the process evaluation, (5) implications for the project, policy and research practice and (6) lessons for future process evaluations. The information was summarized and reported descriptively and narratively and key lessons were identified. Results The case studies were from low- and middle-income countries and Indigenous communities in Canada. They were implementation research projects with intervention arm. Six theoretical approaches were used but most comprised of mixed-methods approaches. Each of the process evaluations generated findings on whether interventions were implemented with fidelity, the extent of capacity building, contextual factors and the extent to which relationships between researchers and community impacted on intervention implementation. The most important learning was that although process evaluation is time consuming, it enhances understanding of factors affecting implementation of complex interventions. The research highlighted the need to initiate process evaluations early on in the project, to help guide design of the intervention; and the importance of effective communication between researchers responsible for trial implementation, process evaluation and outcome evaluation. Conclusion This research demonstrates the important role of process evaluation in understanding implementation process of complex interventions. This can help to highlight a broad range of system requirements such as new policies and capacity building to support implementation. Process evaluation is crucial in understanding contextual factors that may impact intervention implementation which is important in considering whether or not the intervention can be translated to other contexts.

Over 907,000 Rohingya refugees are currently living in mostly makeshift camps in Bangladesh with limited resources to address their psychosocial needs. Physical activity is a scalable, low-cost intervention effective for prevention and treatment of non-communicable diseases and mental health problems. Understanding community attitudes to physical activity and mental health is key to designing community endorsed and accessible interventions. We employed the ‘community readiness model’, a tool to assess community climate, needs and resources regarding physical activity as a community-driven psychosocial intervention. Fifteen Rohingya key informants were interviewed across multiple refugee camps in Cox’s Bazaar district in January 2019. Community readiness scores were calculated. Thematic analysis explored community-identified priorities. Community members strongly endorsed physical activity as an effective biopsychosocial strategy for relieving tension (a local idiom of distress). Despite leadership endorsement, space and resources to support community initiatives are extremely limited. For women, restrictions of movement were identified as barriers to participation. Physical activity is a feasible and acceptable community-identified strategy to promote psychosocial wellbeing among Rohingya refugees. Resources for physical activity programmes are extremely limited despite the identified social, mental and physical health benefits. Key implications for practice Physical activity was identified as a psychosocial strategy by Rohingya refugees living in Cox’s Bazar, Bangladesh, which can help to relieve tension, which is a local idiom of distress. Resources (such as space and equipment) to support community-led physical activity initiatives are limited, despite support from community leadership. Access to physical activity is limited for women, due to security fears and cultural attitudes, as well as for people with disabilities and older people, due to overcrowding and lack of accessibility planning.

The rising global burden of chronic non-communicable diseases (NCDs) has put a strain on healthcare systems globally, especially in low- and middle-income countries, which have seen disproportionate mortality rates due to non-communicable diseases. These deaths are in part due to challenges with medication adherence, which are compounded by lack of access to medication and weak community support systems. This paper aims to propose a potential solution using models of service delivery in HIV/AIDS, given the many similarities between NCD and HIV/AIDS. Models that have been particularly effective in HIV/AIDS are the community-based peer-support medication delivery groups: medication adherence clubs and community antiretroviral therapy (ART) groups. The positive outcomes from these models, including improved medication adherence and patient satisfaction, provide evidence for their potential success when applied to non-communicable diseases, particularly hypertension and cardiovascular disease.

My aim in this paper is to explore some metaphysical and psychological implications of the (contentious) idealist interpretation of the belief in external objects ("bodies") Hume ascribes to us in the Treatise. More specifically, I will argue that the interpretation commits Hume to the claim that space is spatially fragmented, both synchronically and (even more so) diachronically, and renders Hume incapable of allowing for all the spatial thoughts we think we can have. But (perhaps surprisingly) it does not impugn Hume's view of causation.

OBJECTIVES/GOALS: As the number of older adults (≥65 years) with T1D grows, there are limited data to guide care. In a six-month trial, CGM reduced hypoglycemia in older adults, yet there are challenges for widespread uptake. Our objective is to characterize older adults experiences with using CGM and define suboptimal responses signaling a need for resources or support. METHODS/STUDY POPULATION: The study will engage key stakeholders (i.e., older adults with T1D, caregivers [recruited as patient-caregiver dyads], and providers [endocrinologists, geriatricians, diabetes educators]) for a Group Model Building (GMB). GMB is a participatory approach to system dynamics in which participants share perceptions and experiences with a problem and collaboratively explore the system structure that shapes those trends. A series of 8 GMB workshops will be held with 3-8 participants. The final study n will be determined by thematic saturation. Workshops comprise 1) a questionnaire, 2) a GMB session, and 3) a focus group discussion. GMB will follow a replicable process to generate a model of the complex web of causal determinants affecting CGM-related experiences, including optimal and suboptimal CGM responses. RESULTS/ANTICIPATED RESULTS: To date, the study has enrolled 33 participants, including 28 older adults living with T1D and 5 caregivers (mean age = 74 years, range 67-83 years). Twenty-four patient participants will be active CGM users and 4 will be CGM non-users. The study will report on patient data capture from the questionnaire and EMR, including demographics, experiences, familiarity, and confidence surrounding CGM use; diabetes duration; insulin pump use; history of severe hypoglycemia. Analysis of aggregated data will generate causal loop diagrams that integrate pertinent theoretical frameworks, lived experiences, and CGM outcomes. Maps will be used to identify a set of suboptimal CGM responses (i.e., key outcome trajectories) that signal a need for action, with a diagram of factors that interact to produce each response. DISCUSSION/SIGNIFICANCE: Delivering CGM to older adults with T1D demands new approaches. This study will yield critical evidence to tailor support and resources for effective CGM use in older adults. Findings may be translated into suite of pragmatic interventions to bolster CGM use and matched to individual patients expected to benefit using a precision medicine framework.

While the roles of a few specific lipids in plant freezing tolerance are understood, the effect of many plant lipids remains to be determined. Acclimation of plants to non-freezing cold before exposure to freezing temperatures improves the outcome of plants, compared to plants exposed to freezing without acclimation. Arabidopsis thaliana plants were subjected to one of three treatments: (1) “control”, i.e., growth at 21 °C, (2) “non-acclimated”, i.e., 3 days at 21 °C, 2 h at −8 °C, and 24 h recovery at 21 °C, and (3) “acclimated”, i.e., 3 days at 4 °C, 2 h at −8 °C, and 24 h recovery at 21 °C. Plants were harvested at seven time points during the treatments, and lipid levels were measured by direct-infusion electrospray ionization tandem mass spectrometry. Ion leakage was measured at the same time points. To examine the function of lipid species in relation to freezing tolerance, the lipid levels in plants immediately following the freezing treatment were correlated with the outcome, i.e., ion leakage 24-h post-freezing. Based on the correlations, hypotheses about the functions of specific lipids were generated. Additionally, analysis of the lipid levels in plants with mutations in genes encoding patatin-like phospholipases, lipoxygenases, and 12-oxophytodienoic acid reductase 3 (opr3), under the same treatments as the wild-type plants, identified only the opr3-2 mutant as having major lipid compositional differences compared to wild-type plants.

BACKGROUND Internationally, most atrial fibrillation (AF) management guidelines recommend opportunistic screening for AF in people ≥65 years of age and oral anticoagulant treatment for those at high stroke risk (CHA₂DS₂‐VA≥2). However, gaps remain in screening and treatment. METHODS AND RESULTS General practitioners/nurses at practices in rural Australia (n=8) screened eligible patients (≥65 years of age without AF) using a smartphone ECG during practice visits. eHealth tools included electronic prompts, guideline‐based electronic decision support, and regular data reports. Clinical audit tools extracted de‐identified data. Results were compared with an earlier study in metropolitan practices (n=8) and nonrandomized control practices (n=69). Cost‐effectiveness analysis compared population‐based screening with no screening and included screening, treatment, and hospitalization costs for stroke and serious bleeding events. Patients (n=3103, 34%) were screened (mean age, 75.1±6.8 years; 47% men) and 36 (1.2%) new AF cases were confirmed (mean age, 77.0 years; 64% men; mean CHA₂DS₂‐VA, 3.2). Oral anticoagulant treatment rates for patients with CHA₂DS₂‐VA≥2 were 82% (screen detected) versus 74% (preexisting AF)(P=NS), similar to metropolitan and nonrandomized control practices. The incremental cost‐effectiveness ratio for population‐based screening was AU$16 578 per quality‐adjusted life year gained and AU$84 383 per stroke prevented compared with no screening. National implementation would prevent 147 strokes per year. Increasing the proportion screened to 75% would prevent 177 additional strokes per year. CONCLUSIONS An AF screening program in rural practices, supported by eHealth tools, screened 34% of eligible patients and was cost‐effective. Oral anticoagulant treatment rates were relatively high at baseline, trending upward during the study. Increasing the proportion screened would prevent many more strokes with minimal incremental cost‐effectiveness ratio change. eHealth tools, including data reports, may be a valuable addition to future programs. REGISTRATION URL: https://www.anzctr.org.au. Unique identifier: ACTRN12618000004268.

Highlights: Despite clinical evidence of its effectiveness in secondary prevention of cardiovascular disease, uptake of fixed dose combination therapy (FDCs) for CVD has been poor. A symposium was held bringing together stakeholders on this issue, including from academia, government and NGOs. The conclusion made was that what is now needed to improve implementation of FDCs is country-specific health systems analyses to design appropriate implementation strategies. Implementation strategies must look beyond listing on the WHO Essential Medicines List to consider approaches to improving FDC availability, accessibility, affordability, and adherence. Strategies might include incorporation of FDCs into the WHO HEARTS technical package, simplified treatment and monitoring algorithms, decentralisation of medicine dispensing and task-sharing for treatment management.

Explorations of the relationship between Artificial Intelligence (AI), the arts, and design have existed throughout the historical development of AI. We are currently witnessing exponential growth in the application of Machine Learning (ML) and AI in all domains of art (visual, sonic, performing, spatial, transmedia, audiovisual, and narrative) in parallel with activity in the field that is so rapid that publication can not keep pace. In dialogue with our contemplation about this development in the arts, authors in this issue answer with questions of their own. Through questioning authorship and ethics, autonomy and automation, exploring the contribution of art to AI, algorithmic bias, control structures, machine intelligence in public art, formalization of aesthetics, the production of culture, socio-technical dimensions, relationships to games and aesthetics, and democratization of machine-based creative tools the contributors provide a multifaceted view into crucial dimensions of the present and future of creative AI. In this Artnodes special issue, we pose the question: Does generative and machine creativity in the arts and design represent an evolution of “artistic intelligence,” or is it a metamorphosis of creative practice yielding fundamentally distinct forms and modes of authorship?

Abstract Background Lipidomics plays an important role in understanding plant adaptation to different stresses and improving our knowledge of the genes underlying lipid metabolism. Lipidomics involves lipid extraction, sample preparation, mass spectrometry analysis, and data interpretation. One of the practical challenges for large-scale lipidomics studies on plant leaves is the requirement of an efficient and rapid extraction method. Results A single-extraction method with a polar solvent mixture gives results comparable to a widely used, multi-extraction method when tested on both Arabidopsis thaliana and Sorghum bicolor leaf tissue. This single-extraction method uses a mixture of 30 parts chloroform, 25 parts isopropanol, 41.5 parts methanol, and 3.5 parts water (v/v/v/v) and a 24-h extraction time. Neither inclusion of ammonium acetate nor inclusion of acetic acid increased extraction efficiency. Conclusions The extract produced by this method can be used for analysis by mass spectrometry without a solvent evaporation step. The amount of lipid extracted, including phosphatidic acid, is comparable to widely used, more labor-intensive methods. The single-extraction protocol is less laborious, reducing the potential for human error.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950–Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Abstract Background In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure ($932 per year P

This is a phase II dose escalation trial of carfilzomib in combination with thalidomide and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The results of four dose levels are reported. Induction therapy consisted of four cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21), and 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, 16 of a 28-day cycle; thalidomide 200 mg on day 1 through 28 and dexamethasone 40 mg weekly. Induction therapy was followed by high-dose melphalan and autologous stem cell transplantation and consolidation therapy with four cycles of carfilzomib, thalidomide and dexamethasone in the same schedule except a lower dose of thalidomide (50 mg). Very good partial response rate or better and complete response rate or better after induction therapy were 65% and 18%, respectively, increasing to 86% and 63%, respectively, after consolidation therapy. In all cohorts combined, after a median follow up of 58.7 months, median progression-free survival was 58 months (95%CI: 45-67 months). Median overall survival was 83 months (95%CI: 83 months-not reached). Grade 3/4 adverse events consisted mainly of infections, respiratory disorders, skin and vascular disorders in 11%, 8%, 9%, and 9%, respectively. Grade 3 polyneuropathy was only reported in one patient. Cardiac events were limited: grade 3/4 in 5% of patients. Carfilzomib, thalidomide and dexamethasone as induction and consolidation treatment after high-dose melphalan and autologous stem cell transplantation is highly efficacious and safe in transplant-eligible patients with NDMM. This study was registered as #NTR2422 at http://www.trialregister.nl