Economic issues in a trial of the controlled provision of heroin

Executive Summary: This paper discusses some economic issues that may be investigated as part of a proposed trial of the controlled provision of heroin in the Australian Capital Territory. Such a trial would provide an opportunity to gather empirical evidence on some aspects of the operation of the market for heroin. Specifically, it would enable the investigation of the extent to which purity, rather than price, is the equilibrating mechanism in this market. If purity is an important equilibrating mechanism, then provision of heroin of constant purity to trial participants would yield important health benefits to those participants. However, if purity on the black market is increased in economic retaliation against a trial, there may be unintended adverse effects on the health of black market users in the short run. In the long run, stabilisation of purity on the black market may be associated with an improvement in the health status of non-trial users. An important issue that cannot be addressed in the context of the proposed trial is the price elasticity of demand for heroin, that is, the responsiveness of demand for heroin to a change in its price. The use of pre–specified criteria to determine eligibility for participation in a trial will preclude any estimation of the increase in demand for heroin attributable to a fall in its price

Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes.

Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR) for thrombin and promotes inflammatory responses through multiple pathways including p38 mitogen-activated protein kinase signaling. The mechanisms that govern PAR1-induced p38 activation remain unclear. Here, we define an atypical ubiquitin-dependent pathway for p38 activation used by PAR1 that regulates endothelial barrier permeability. Activated PAR1 K63-linked ubiquitination is mediated by the NEDD4-2 E3 ubiquitin ligase and initiated recruitment of transforming growth factor-β-activated protein kinase-1 binding protein-2 (TAB2). The ubiquitin-binding domain of TAB2 was essential for recruitment to PAR1-containing endosomes. TAB2 associated with TAB1, which induced p38 activation independent of MKK3 and MKK6. The P2Y1 purinergic GPCR also stimulated p38 activation via NEDD4-2-mediated ubiquitination and TAB1-TAB2. TAB1-TAB2-dependent p38 activation was critical for PAR1-promoted endothelial barrier permeability in vitro, and p38 signaling was required for PAR1-induced vascular leakage in vivo. These studies define an atypical ubiquitin-mediated signaling pathway used by a subset of GPCRs that regulates endosomal p38 signaling and endothelial barrier disruption

Chronic pain, pain severity and analgesia use in Australian women of reproductive age

BACKGROUND: The increasing prevalence and adverse outcomes associated with opioid analgesia use in women of reproductive age have become a significant public health issue internationally, with use during pregnancy potentially affecting maternal and infant health outcomes. OBJECTIVE: This study aims to provide national estimates of chronic pain, pain severity and analgesia use in Australian women of reproductive age by pregnancy status. METHOD: Data were obtained from the Australian Bureau of Statistics 2011-12 National Health Survey (n=20,426). Weighting was applied to sample data to obtain population estimates. For this study data were analysed for pregnant (n=166, N=192,617) and non-pregnant women (n=4710, N=5,256,154) of reproductive age (15-49 years). RESULTS: Chronic or reoccurring pain was reported in 5.1% of pregnant women and 9.7% of non-pregnant women, and 0.7% and 2.6% of pregnant and non-pregnant women reported recent opioid analgesia use respectively. Moderate-to-very severe pain was more common in pregnant than non-pregnant women taking opioid analgesics, and no pain and very mild-to-mild pain in non-pregnant women. CONCLUSION: Approximately 1 in 20 pregnant Australian women have chronic or reoccurring pain. Opioid analgesia was used by around 1% of Australian pregnant women during a two-week period, with use associated with moderate-to-very severe pain. Given that the safety of many analgesic medications in pregnancy remains unknown, pregnant women and health professionals require accurate, up-to-date information on the risks and benefits of analgesic use during pregnancy. Further evidence on the decision-making processes of pregnant women with pain should assist health professionals maximise outcomes for mothers and infants

The evolution of social health insurance in Vietnam and its role towards achieving universal health coverage

Our research examines the development of social health insurance (SHI) in Vietnam between 1992 and 2016 and SHI's role as a financial mechanism towards achieving universal health coverage (UHC). We reviewed and analysed legislation from the Government of Vietnam (GoV) and performance data from the GoV and the World Bank. Stages of development were identified from legislative change leading to change in SHI functioning as a public financing mechanism: revenue collection, pooling of risk, and purchasing. Movement towards UHC was assessed relative to: population coverage, benefit coverage, and financial protection. Vietnam has implemented SHI through five stages: Stage I (1992–1998), Stage II (1998–2005), Stage III (2005–2008), Stage IV (2008–2014), and Stage V (2014 onwards). Coverage has widened from a compulsory scheme for civil servants and pensioners and a voluntary scheme for others, to a scheme that targets the entire population. However, UHC has not been achieved with 19% of the population uninsured in 2016 and high out-of-pocket payments. The benefit package includes a wide range of services and many expensive medications and considered to be generous. It is recommended that Vietnam focus on improving population coverage rather than further expanding the benefit package to achieve UHC

A systematic review and meta-analysis of workplace mindfulness training randomized controlled trials

This meta-analytic review responds to promises in the research literature and public domain about the benefits of workplace mindfulness training. It synthesizes randomized controlled trial evidence from workplace-delivered training for changes in mindfulness, stress, mental health, well-being, and work performance outcomes. Going beyond extant reviews, this article explores the influence of variability in workforce and intervention characteristics for reducing perceived stress. Meta-effect estimates (Hedge’s g) were computed using data from 23 studies. Results indicate beneficial effects following training for mindfulness (g = 0.45, p < .001) and stress (g = 0.56, p < .001), anxiety (g = 0.62, p < .001) and psychological distress (g = 0.69, p < .001), and for well-being (g = 0.46, p = .002) and sleep (g = 0.26, p = .003). No conclusions could be drawn from pooled data for burnout due to ambivalence in results, for depression due to publication bias, or for work performance due to insufficient data. The potential for integrating the construct of mindfulness within job demands-resources, coping, and prevention theories of work stress is considered in relation to the results. Limitations to study designs and reporting are addressed, and recommendations to advance research in this field are made. (PsycINFO Database Record (c) 2019 APA, all rights reserved

The effect of exercise intensity on cognitive performance during short duration treadmill running

This study examined the effect of short duration, moderate and high-intensity exercise on a Go/NoGo task. Fifteen, habitually active (9 females and 6 males aged 28 ± 5 years) agreed to participate in the study and cognitive performance was measured in three sessions lasting 10 min each, performed at three different exercise intensities: rest, moderate and high. Results indicated significant exercise intensity main effects for reaction time (RT) (p = 0.01), the omission error rate (p = 0.027) and the decision error rate (p = 0.011), with significantly longer RTs during high intensity exercise compared to moderate intensity exercise (p = 0.039) and rest (p = 0.023). Mean ± SE of RT (ms) was 395.8 ± 9.1, 396.3 ± 9.1 and 433.5 ± 16.1 for rest, moderate and high intensity exercise, respectively. This pattern was replicated for the error rate with a significantly higher omission error and decision error rate during high intensity exercise compared to moderate intensity exercise (p = 0.003) and rest (p = 0.001). Mean ± SE of omission errors (%) was 0.88 ± 0.23, 0.8 ± 0.23 and 1.8 ± 0.46% for rest, moderate and high intensity exercise, respectively. Likewise, mean ± SE of decision errors (%) was 0.73 ± 0.24, 0.73 ± 0.21 and 1.8 ± 0.31 for rest, moderate and high intensity exercise, respectively. The present study’s results suggest that 10 min workout at high intensity impairs RT performances in habitually active adults compared to rest or moderate intensity exercise

Mucosal adjuvants and delivery systems

Adjuvants comprising chitosan cross-linked with an aldehyde or mannosylated chitosan are provided herein. Methods of making the adjuvants and methods of combining or linking the adjuvants with antigens are also provided. The adjuvant-antigen combinations can be used in vaccine formulations and the vaccine formulations can be used in methods to vaccinate animals against the source of the antigen or to enhance the immune response in a subject

Collaborative development of the Arrowsmith two node search interface designed for laboratory investigators.

Arrowsmith is a unique computer-assisted strategy designed to assist investigators in detecting biologically-relevant connections between two disparate sets of articles in Medline. This paper describes how an inter-institutional consortium of neuroscientists used the UIC Arrowsmith web interface http://arrowsmith.psych.uic.edu in their daily work and guided the development, refinement and expansion of the system into a suite of tools intended for use by the wider scientific community

Muddy waters: efficacious predation of container-breeding mosquitoes by a newly-described calanoid copepod across differential water clarities

Mosquito-borne diseases induce unrivalled morbidity and mortality in human populations. In recent times, greater urbanisation has facilitated vector population expansion, particularly of those which proliferate in container-style habitats. To combat increased associated disease risk, we urgently require innovative and efficacious control mechanisms to be identified and implemented. Predatory biological control of vectorially-important mosquitoes can be effective. Despite their high prevalence in freshwater ecosystems, predatory calanoid copepods have yet to be examined comprehensively for mosquito control. Moreover, environmental context-dependencies can cause substantial variations in natural enemy impacts on target populations. Accordingly, improved understanding of the effects of context-dependencies upon predatory biocontrol is needed. Here, we use functional responses (FRs) to examine the predatory impact of a newly-described species of calanoid copepod, Lovenula raynerae, upon larval Culex pipiens prey across variations in prey supply and water clarity. Using outdoor field trials, we assess the viability of L. raynerae in reducing mosquito survival in container-style habitats. Lovenula raynerae displayed destabilising Type II FRs towards larval mosquito prey across all water clarities tested, with overall predation rates remaining largely unaffected across all clarity treatments. In the outdoor experiment, L. raynerae applications resulted in substantial reductions in larval C. pipiens populations, with close to total eradication achieved following the experimental period under higher predator densities. These results demonstrate that environmental context such as water clarity may have little effect on vector control by calanoid copepods, which suggests a predatory reliance on hydromechanical signalling. Further, for the first time, we demonstrate the applicability of calanoid copepods to artificial container-style habitats where mosquitoes proliferate. Therefore, our results indicate that further examination into the applicability of this species group to aid vector biocontrol strategies is warranted