Atom-economic access to cationic magnesium complexes.

Cationic alkaline-earth complexes attract interest for their enhanced Lewis acidity and reactivity compared with their neutral counterparts. Synthetic protocols to these complexes generally utilize expensive specialized reagents in reactions generating multiple by-products. We have studied a simple ligand transfer approach to these complexes using (NacNac)MgR and ER3 (NacNac = ß-diketiminate anion; E = group 13 element; R = aryl/amido anion) which demonstrates high atom economy, opening up the ability to target these species in a more sustainable manner. The success of this methodology is dependent on the identity of the group 13 element with the heavier elements facilitating faster ligand exchange. Furthermore, while this reaction is successful with aromatic ligands such as phenyl and pyrrolyl, the secondary amide piperidide (pip) fails to transfer, which we attribute to the stronger 3-centre-4-electron dimerization interaction of Al2(pip)6.

Health impact assessment for air pollution in the presence of regional variation in effect sizes: The implications of using different meta-analytic approaches.

The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO2, O3 and PM2.5 with all-cause mortality, and PM2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran's Q test has a higher median power (0.71) than a test based on the moderators' coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09).

The role of burden of disease assessment in tracking progress towards achieving WHO global air quality guidelines.

OBJECTIVES: More than 90% of the global population live in areas exceeding the PM2.5 air quality guidelines (AQGs). We provide an overview of the ambient PM2.5-related burden of disease (BoD) studies along with scenario analysis in the framework of the WHO AQG update on the estimated reduction in the BoD if AQGs were achieved globally. METHODS: We reviewed the literature for large-scale studies for the BoD attributed to ambient PM2.5. Moreover, we used the latest WHO statistics to calculate the BoD at current levels and the scenarios of aligning with interim targets and AQG levels. RESULTS: The most recent BoD studies (2010 onwards) share a similar methodology, but there are differences in the input data which affect the estimates for attributable deaths (2.9-8.9 million deaths annually). Moreover, we found that if AQGs were achieved, the estimated BoD would be reduced by up to 50% in total deaths worldwide. CONCLUSIONS: Understanding the BoD across countries, especially in those that do not align with the AQGs, is essential in order to inform actions to reduce air pollution globally.

Using epidemiology to estimate the impact and burden of exposure to air pollutants.

This paper focuses on the use of results of epidemiological studies to quantify the effects on health, particularly on mortality, of long-term exposure to air pollutants. It introduces health impact assessment methods, used to predict the benefits that can be expected from implementation of interventions to reduce emissions of pollutants. It also explains the estimation of annual mortality burdens attributable to current levels of pollution. Burden estimates are intended to meet the need to communicate the size of the effect of air pollution on public health to policy makers and others. The implications, for the interpretation of the estimates, of the assumptions and approximations underlying the methods are discussed. The paper starts with quantification based on results obtained from studies of the association of mortality risk with long-term average concentrations of particulate air pollution. It then tackles the additional methodological considerations that need to be addressed when also considering the mortality effects of other pollutants such as nitrogen dioxide (NO2). Finally, approaches that could be used to integrate morbidity and mortality endpoints in the same assessment are touched upon. This article is part of a discussion meeting issue 'Air quality, past present and future'.

The Lancet Countdown on health benefits from the UK Climate Change Act: a modelling study for Great Britain.

BACKGROUND: Climate change poses a dangerous and immediate threat to the health of populations in the UK and worldwide. We aimed to model different scenarios to assess the health co-benefits that result from mitigation actions. METHODS: In this modelling study, we combined a detailed techno-economic energy systems model (UK TIMES), air pollutant emission inventories, a sophisticated air pollution model (Community Multi-scale Air Quality), and previously published associations between concentrations and health outcomes. We used four scenarios and focused on the air pollution implications from fine particulate matter (PM2·5), nitrogen dioxide (NO2) and ozone. The four scenarios were baseline, which assumed no further climate actions beyond those already achieved and did not meet the UK's Climate Change Act (at least an 80% reduction in carbon dioxide equivalent emissions by 2050 compared with 1990) target; nuclear power, which met the Climate Change Act target with a limited increase in nuclear power; low-greenhouse gas, which met the Climate Change Act target without any policy constraint on nuclear build; and a constant scenario that held 2011 air pollutant concentrations constant until 2050. We predicted the health and economic impacts from air pollution for the scenarios until 2050, and the inequalities in exposure across different socioeconomic groups. FINDINGS: NO2 concentrations declined leading to 4 892 000 life-years saved for the nuclear power scenario and 7 178 000 life-years saved for the low-greenhouse gas scenario from 2011 to 2154. However, the associations that we used might overestimate the effects of NO2 itself. PM2·5 concentrations in Great Britain are predicted to decrease between 42% and 44% by 2050 compared with 2011 in the scenarios that met the Climate Change Act targets, especially those from road traffic and off-road machinery. These reductions in PM2·5 are tempered by a 2035 peak (and subsequent decline) in biomass (wood burning), and by a large, projected increase in future demand for transport leading to potential increases in non-exhaust particulate matter emissions. The potential use of biomass in poorly controlled technologies to meet the Climate Change Act commitments would represent an important missed opportunity (resulting in 472 000 more life-years lost from PM2·5 in the low-greenhouse gas scenario and 1 122 000 more life-years lost in the nuclear power scenario from PM2·5 than the baseline scenario). Although substantial overall improvements in absolute amounts of exposure are seen compared with 2011, these outcomes mask the fact that health inequalities seen (in which socioeconomically disadvantaged populations are among the most exposed) are projected to be maintained up to 2050. INTERPRETATION: The modelling infrastructure created will help future researchers explore a wider range of climate policy scenarios, including local, European, and global scenarios. The need to strengthen the links between climate change policy objectives and public health imperatives, and the benefits to societal wellbeing that might result is urgent. FUNDING: National Institute for Health Research.

Advancing LGBT Health Care Policies and Clinical Care Within a Large Academic Health Care System: A Case Study.

Culturally competent health care is especially important among sexual and gender minority patients because poor cultural competence contributes to health disparities. There is a need to understand how to improve health care quality and delivery for lesbian, gay, bisexual, and transgender (LGBT) veterans in particular, because they have unique physical and mental health needs as both LGBT individuals and veterans. The following article is a case study that focuses on the policy and clinical care practices related to LGBT clinical competency, professional training, and ethical provision of care for veteran patients in the VA Boston Healthcare System. We apply Betancourt et al.'s (2003) cultural competence framework to outline the steps that VA Boston Healthcare System took to increase cultural competency at the organizational, structural, and clinical level. By sharing our experiences, we aim to provide a model and steps for other health care systems and programs, including other VA health care systems, large academic health care systems, community health care systems, and mental health care systems, interested in developing LGBT health initiatives.

The psychologist's role in transgender-specific care with U.S. veterans.

Psychologists are integral to the care of transgender individuals. This article details the many roles for psychologists in transgender-specific care, including diagnosing and treating gender dysphoria; providing treatment for comorbid conditions; referring to medical services such as gender confirmation surgeries, voice modification, and cross-sex hormone therapies; serving as consultants within health care systems; and advocating for addressing barriers in systems in which transgender individuals live and work. Transgender veterans have unique experiences and vulnerabilities related to their military service that are detailed from a review of the literature, and we make the case that Veterans Health Administration (VHA) and community psychologists are well-positioned to provide care to transgender veterans (trans-vets). In this article, the authors describe the experiences that many trans-vets have faced, identify the importance of treatment for gender dysphoria (and draw the distinction between gender identity disorder and gender dysphoria) as well as psychologists' roles, and clarify which transgender-related services are available to eligible veterans though VHA per policy and how VHA providers have access to training to provide that care. In addition, we describe how veterans can connect to the VHA, even if they have (and want to continue working with) non-VHA psychologists or other community providers.

Quantifying the health impacts of ambient air pollutants: recommendations of a WHO/Europe project.

OBJECTIVE: Quantitative estimates of air pollution health impacts have become an increasingly critical input to policy decisions. The WHO project "Health risks of air pollution in Europe--HRAPIE" was implemented to provide the evidence-based concentration-response functions for quantifying air pollution health impacts to support the 2013 revision of the air quality policy for the European Union (EU). METHODS: A group of experts convened by WHO Regional Office for Europe reviewed the accumulated primary research evidence together with some commissioned reviews and recommended concentration-response functions for air pollutant-health outcome pairs for which there was sufficient evidence for a causal association. RESULTS: The concentration-response functions link several indicators of mortality and morbidity with short- and long-term exposure to particulate matter, ozone and nitrogen dioxide. The project also provides guidance on the use of these functions and associated baseline health information in the cost-benefit analysis. CONCLUSIONS: The project results provide the scientific basis for formulating policy actions to improve air quality and thereby reduce the burden of disease associated with air pollution in Europe.

Monitoring air pollution: use of early warning systems for public health.

Research confirming the detrimental impact poor ambient air quality and episodes of abnormally high pollutants has on public health, plus differential susceptibility, calls for improved understanding of this complex topic among all walks of society. The public and particularly, vulnerable groups, should be aware of their quality of air, enabling action to be taken in the event of increased pollution. Policy makers must have a sound awareness of current air quality and future trends, to identify issues, guide policies and monitor their effectiveness. These attitudes are dependent upon air pollution monitoring, forecasting and reporting, serving all interested parties. Apart from the underlying national regulatory obligation a country has in reporting air quality information, data output serves several purposes. This review focuses on provision of real-time data and advanced warnings of potentially health-damaging events, in the form of national air quality indices and proactive alert services. Some of the challenges associated with designing these systems include technical issues associated with the complexity of air pollution and its science. These include inability to provide precise exposure concentrations or guidance on long-term/cumulative exposures or effects from pollutant combinations. Other issues relate to the degree to which people are aware and positively respond to these services. Looking to the future, mobile devices such as cellular phones, equipped with sensing applications have potential to provide dynamic, temporally and spatially precise exposure measures for the mass population. The ultimate aim should be to empower people to modify behaviour-for example, when to increase medication, the route/mode of transport taken to school or work or the appropriate time to pursue outdoor activities-in a way that protects their health as well as the quality of the air they breathe.

Are we there yet? The four-year impact of a VA fellowship program on the recovery orientation of rehabilitation programs.

OBJECTIVE: This study represents the first program evaluation of the impact of a Psychosocial Rehabilitation (PSR) fellowship program within the Veterans Health Administration (VHA). Specifically, it examines the recovery orientation of five mental health rehabilitation programs at the Edith Nourse Rogers Memorial VA Medical Center (ENRM VAMC) in Bedford, MA by comparing program stakeholder rating of the "recovery orientation" between the initial data and the four-year follow-up during which the PSR fellowship was in operation. The goal of this fellowship program is to increase the VHA's fidelity to recovery-oriented best practice recommendations. METHOD: Participants were mental health consumers and staff members within five key psychiatric rehabilitation programs at the ENRM VAMC. Perception of programs' recovery orientation was measured at the start of the fellowship (Time 1) and after the fellowship was in place for four years (Time 2). RESULTS: Results demonstrate that across the entire sample of stakeholders, perceptions of recovery orientation significantly improved from Time 1 to Time 2. Results also reveal a significant overall increase in program recovery orientation over time in three out of the five rehabilitation programs, with years of fellow involvement in particular programs significantly and positively correlating with increases in ratings of program recovery-orientation gains. DISCUSSION: Implications for using fellowships as agents of program change, and specifically, recovery-oriented change, are discussed.

An examination of interventions to reduce respiratory health and injury hazards in homes of low-income families.

We evaluated whether combining asthma trigger reduction with housing structural repairs, device disbursement and education in low-income households with children would improve self-reported respiratory health and reduce housing-related respiratory health and injury hazards (convenience sample of n=67 homes with 63 asthmatic and 121 non-asthmatic children). At baseline, a visual assessment of the home environment and a structured occupant interview were used to examine 29 potential injury hazards and 7 potential respiratory health hazards. A home-specific intervention was designed to provide the children's parents or caretakers with the knowledge, skills, motivation, supplies, equipment, and minimum housing conditions necessary for a healthy and safe home. The enrolled households were primarily Hispanic and owned their homes. On average, 8 injury hazards were observed in the homes at baseline. Four months following intervention, the average declined to 2.2 hazards per home (p<0.001), with 97% of the parents reporting that their homes were safer following the interventions. An average of 3.3 respiratory health hazards were observed in the homes at baseline. Four months following intervention, the average declined to 0.9 hazards per home (p<0.001), with 96% of parents reporting that the respiratory health of their asthmatic children improved. A tailored healthy homes improvement package significantly improves self-reported respiratory health and safety, reduces respiratory health and injury hazards, and can be implemented in concert with a mobile clinical setting.

Analysis of multiple exon-skipping mRNA splice variants using SYBR Green real-time RT-PCR.

Fluorescence-based PCR techniques are becoming an increasingly popular method for measuring low-abundance alternatively spliced mRNA transcripts. The dynamic range of real-time RT-PCR affords high sensitivity for the measurement of gene expression, but this mandates the need for strict controls to ensure assay validity. Primer design, reverse transcription, and cycling conditions need to be optimized to ensure an accurate and reproducible assay. Here, we describe a procedure for creating a cost effective and reliable method for the absolute quantification of several exon-skipping variants of human excitatory amino acid transporter-2 (EAAT2). We show that the cycling conditions can be adjusted to increase the specificity of primers that span exon-exon junctions, and that differences in the reverse transcription reaction can be minimized. Standard curves are stable and produce accurate absolute copy number data. We report that exon-skipping transcripts, EAAT2Delta7 and EAAT2Delta9, account for 5.8% of EAAT2 mRNA in autopsy human neocortex.