Personal exposure to air pollution and respiratory health of COPD patients in London.

Previous studies have investigated the effects of air pollution on chronic obstructive pulmonary disease (COPD) patients using either fixed-site measurements or a limited number of personal measurements, usually for one pollutant and a short time period. These limitations may introduce bias and distort the epidemiological associations as they do not account for all the potential sources or the temporal variability of pollution.We used detailed information on individuals' exposure to various pollutants measured at fine spatiotemporal scale to obtain more reliable effect estimates. A panel of 115 patients was followed up for an average continuous period of 128 days carrying a personal monitor specifically designed for this project that measured temperature, nitrogen dioxide (NO2), ozone (O3), nitric oxide (NO), carbon monoxide (CO), and particulate matter with aerodynamic diameter <2.5 and <10 µm at 1-min time resolution. Each patient recorded daily information on respiratory symptoms and measured peak expiratory flow (PEF). A pulmonologist combined related data to define a binary variable denoting an "exacerbation". The exposure-response associations were assessed with mixed effects models.We found that gaseous pollutants were associated with a deterioration in patients' health. We observed an increase of 16.4% (95% CI 8.6-24.6%), 9.4% (95% CI 5.4-13.6%) and 7.6% (95% CI 3.0-12.4%) in the odds of exacerbation for an interquartile range increase in NO2, NO and CO, respectively. Similar results were obtained for cough and sputum. O3 was found to have adverse associations with PEF and breathlessness. No association was observed between particulate matter and any outcome.Our findings suggest that, when considering total personal exposure to air pollutants, mainly the gaseous pollutants affect COPD patients' health.

Quantifying the short-term effects of air pollution on health in the presence of exposure measurement error: a simulation study of multi-pollutant model results.

BACKGROUND: Most epidemiological studies estimate associations without considering exposure measurement error. While some studies have estimated the impact of error in single-exposure models we aimed to quantify the effect of measurement error in multi-exposure models, specifically in time-series analysis of PM2.5, NO2, and mortality using simulations, under various plausible scenarios for exposure errors. Measurement error in multi-exposure models can lead to effect transfer where the effect estimate is overestimated for the pollutant estimated with more error to the one estimated with less error. This complicates interpretation of the independent effects of different pollutants and thus the relative importance of reducing their concentrations in air pollution policy. METHODS: Measurement error was defined as the difference between ambient concentrations and personal exposure from outdoor sources. Simulation inputs for error magnitude and variability were informed by the literature. Error-free exposures with their consequent health outcome and error-prone exposures of various error types (classical/Berkson) were generated. Bias was quantified as the relative difference in effect estimates of the error-free and error-prone exposures. RESULTS: Mortality effect estimates were generally underestimated with greater bias observed when low ratios of the true exposure variance over the error variance were assumed (27.4% underestimation for NO2). Higher ratios resulted in smaller, but still substantial bias (up to 19% for both pollutants). Effect transfer was observed indicating that less precise measurements for one pollutant (NO2) yield more bias, while the co-pollutant (PM2.5) associations were found closer to the true. Interestingly, the sum of single-pollutant model effect estimates was found closer to the summed true associations than those from multi-pollutant models, due to cancelling out of confounding and measurement error bias. CONCLUSIONS: Our simulation study indicated an underestimation of true independent health effects of multiple exposures due to measurement error. Using error parameter information in future epidemiological studies should provide more accurate concentration-response functions.

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'.

London Hybrid Exposure Model: Improving Human Exposure Estimates to NO2 and PM2.5 in an Urban Setting.

Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM2.5 and 63% lower for NO2 than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (∼95%), and the mode and duration of travel in London. We find that an individual's exposure to PM2.5 and NO2 outside their residential address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure estimates for PM2.5 and NO2 suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO2 and PM2.5.

Choices of morbidity outcomes and concentration-response functions for health risk assessment of long-term exposure to air pollution.

Background: Air pollution health risk assessment (HRA) has been typically conducted for all causes and cause-specific mortality based on concentration-response functions (CRFs) from meta-analyses that synthesize the evidence on air pollution health effects. There is a need for a similar systematic approach for HRA for morbidity outcomes, which have often been omitted from HRA of air pollution, thus underestimating the full air pollution burden. We aimed to compile from the existing systematic reviews and meta-analyses CRFs for the incidence of several diseases that could be applied in HRA. To achieve this goal, we have developed a comprehensive strategy for the appraisal of the systematic reviews and meta-analyses that examine the relationship between long-term exposure to particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM2.5), nitrogen dioxide (NO2), or ozone (O3) and incidence of various diseases. Methods: To establish the basis for our evaluation, we considered the causality determinations provided by the US Environmental Protection Agency Integrated Science Assessment for PM2.5, NO2, and O3. We developed a list of pollutant/outcome pairs based on these assessments and the evidence of a causal relationship between air pollutants and specific health outcomes. We conducted a comprehensive literature search using two databases and identified 75 relevant systematic reviews and meta-analyses for PM2.5 and NO2. We found no relevant reviews for long-term exposure to ozone. We evaluated the reliability of these studies using an adaptation of the AMSTAR 2 tool, which assesses various characteristics of the reviews, such as literature search, data extraction, statistical analysis, and bias evaluation. The tool's adaptation focused on issues relevant to studies on the health effects of air pollution. Based on our assessment, we selected reviews that could be credible sources of CRF for HRA. We also assessed the confidence in the findings of the selected systematic reviews and meta-analyses as the sources of CRF for HRA. We developed specific criteria for the evaluation, considering factors such as the number of included studies, their geographical distribution, heterogeneity of study results, the statistical significance and precision of the pooled risk estimate in the meta-analysis, and consistency with more recent studies. Based on our assessment, we classified the outcomes into three lists: list A (a reliable quantification of health effects is possible in an HRA), list B+ (HRA is possible, but there is greater uncertainty around the reliability of the CRF compared to those included on list A), and list B- (HRA is not recommended because of the substantial uncertainty of the CRF). Results: In our final evaluation, list A includes six CRFs for PM2.5 (asthma in children, chronic obstructive pulmonary disease, ischemic heart disease events, stroke, hypertension, and lung cancer) and three outcomes for NO2 (asthma in children and in adults, and acute lower respiratory infections in children). Three additional outcomes (diabetes, dementia, and autism spectrum disorders) for PM2.5 were included in list B+. Recommended CRFs are related to the incidence (onset) of the diseases. The International Classification of Diseases, 10th revision codes, age ranges, and suggested concentration ranges are also specified to ensure consistency and applicability in an HRA. No specific suggestions were given for ozone because of the lack of relevant systematic reviews. Conclusion: The suggestions formulated in this study, including CRFs selected from the available systematic reviews, can assist in conducting reliable HRAs and contribute to evidence-based decision-making in public health and environmental policy. Future research should continue to update and refine these suggestions as new evidence becomes available and methodologies evolve.

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).

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.

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.

Associations between sources of particle number and mortality in four European cities.

BACKGROUND: The evidence on the association between ultrafine (UFP) particles and mortality is still inconsistent. Moreover, health effects of specific UFP sources have not been explored. We assessed the impact of UFP sources on daily mortality in Barcelona, Helsinki, London, and Zurich. METHODS: UFP sources were previously identified and quantified for the four cities: daily contributions of photonucleation, two traffic sources (fresh traffic and urban, with size mode around 30 nm and 70 nm, respectively), and secondary aerosols were obtained from data from an urban background station. Different periods were investigated in each city: Barcelona 2013-2016, Helsinki 2009-2016, London 2010-2016, and Zurich 2011-2014. The associations between total particle number concentrations (PNC) and UFP sources and daily (natural, cardiovascular [CVD], and respiratory) mortality were investigated using city-specific generalized linear models (GLM) with quasi-Poisson regression. RESULTS: We found inconsistent results across cities, sources, and lags for associations with natural, CVD, and respiratory mortality. Increased risk was observed for total PNC and natural mortality in Helsinki (lag 2; 1.3% [0.07%, 2.5%]), CVD mortality in Barcelona (lag 1; 3.7% [0.17%, 7.4%]) and Zurich (lag 0; 3.8% [0.31%, 7.4%]), and respiratory mortality in London (lag 3; 2.6% [0.84%, 4.45%]) and Zurich (lag 1; 9.4% [1.0%, 17.9%]). A similar pattern of associations between health outcomes and total PNC was followed by the fresh traffic source, for which we also found the same associations and lags as for total PNC. The urban source (mostly aged traffic) was associated with respiratory mortality in Zurich (lag 1; 12.5% [1.7%, 24.2%]) and London (lag 3; 2.4% [0.90%, 4.0%]) while the secondary source was associated with respiratory mortality in Zurich (lag 1: 12.0% [0.63%, 24.5%]) and Helsinki (4.7% [0.11%, 9.5%]). Reduced risk for the photonucleation source was observed for respiratory mortality in Barcelona (lag 2, -8.6% [-14.5%, -2.4%]) and for CVD mortality in Helsinki, as this source is present only in clean atmospheres (lag 1, -1.48 [-2.75, -0.21]). CONCLUSIONS: We found inconsistent results across cities, sources and lags for associations with natural, CVD, and respiratory mortality.

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.

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.

PM2.5 and NO2 exposure errors using proxy measures, including derived personal exposure from outdoor sources: A systematic review and meta-analysis.

BACKGROUND: The use of proxy exposure estimates for PM2.5 and NO2 in air pollution studies instead of personal exposures, introduces measurement error, which can produce biased epidemiological effect estimates. Most studies consider total personal exposure as the gold standard. However, when studying the effects of ambient air pollution, personal exposure from outdoor sources is the exposure of interest. OBJECTIVES: We assessed the magnitude and variability of exposure measurement error by conducting a systematic review of the differences between personal exposures from outdoor sources and the corresponding measurements for ambient concentrations in order to increase understanding of the measurement error structures of the pollutants. DATA SOURCES AND ELIGIBILITY CRITERIA: We reviewed the literature (ISI Web of Science, Medline, 2000-2016) for English language studies (in any age group in any location (NO2) or Europe and North America (PM2.5)) that reported repeated measurements over time both for personal and ambient PM2.5 or NO2 concentrations. Only a few studies reported personal exposure from outdoor sources. We also collected data for infiltration factors and time-activity patterns of the individuals in order to estimate personal exposures from outdoor sources in every study. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies using modelled rather than monitored exposures were excluded. Type of personal exposure monitor was assessed. Random effects meta-analysis was conducted to quantify exposure error as the mean difference between "true" and proxy measures. RESULTS: Thirty-two papers for PM2.5 and 24 for NO2 were identified. Outdoor sources were found to contribute 44% (range: 33-55%) of total personal exposure to PM2.5 and 74% (range: 57-88%) to NO2. Overall estimates of personal exposure (24-hour averages) from outdoor sources were 9.3 µg/m3 and 12.0 ppb for PM2.5 and NO2 respectively, while the corresponding difference between these exposures and the ambient concentrations (i.e. the measurement error) was 5.72 µg/m3 and 7.17 ppb. Our findings indicated also higher error variability for NO2 than PM2.5. Large heterogeneity was observed which was not explained sufficiently by geographical location or age group of the study sample. LIMITATIONS, CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Relying only on information available in published studies led to some limitations: the contribution of outdoor sources to total personal exposure for NO2 had to be inferred, individual variation in exposure misclassification was unavailable and instrument error could not be addressed. The larger magnitude and variability of errors for NO2 compared with PM2.5 has implications for biases in the health effect estimates of multi-pollutant epidemiological models. Results suggest that further research is needed regarding personal exposure studies and measurement error bias in epidemiological models.

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.

The effect of evidence and theory-based health advice accompanying smartphone air quality alerts on adherence to preventative recommendations during poor air quality days: A randomised controlled trial.

Although poor air quality can have a negative impact on human health, studies have shown suboptimal levels of adherence to health advice associated with air quality alerts. The present study compared the behavioural impact of the UK Air Quality Index (DAQI) with an alternative message format, using a 2 (general population vs. at-risk individuals) X 2 (usual DAQI messages vs. behaviourally enhanced messages) factorial design. Messages were sent via a smartphone application. Eighty-two participants were randomly allocated to the experimental groups. It was found that the enhanced messages (targeting messages specificity and psychosocial predictors of behaviour change) increased intentions to make permanent behavioural changes to reduce exposure, compared to the control group (V = 0.23). This effect was mediated by a reduced perception of not having enough time to follow the health advice received (b = -0.769, BCa CI [-2.588, 0.533]). It was also found that higher worry about air pollution, perceived severity, perceived efficacy of the recommended behaviour and self-efficacy were predictive of self-reported behaviour change at four weeks. In response to a real moderate air quality alert, among those with a pre-existing lung condition, more respondents in the intervention group reported to have used their preventer inhaler compared to the control group (V = 0.49). On the other hand, the two message formats performed similarly when intentions were collected in relation to a hypothetical high air pollution scenario, with all groups showing relatively high intentions to change behaviours. This study expands the currently limited understanding of how to improve the behavioural impact of existing air quality alerts.

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.

Glutamate-glutamine cycling in Alzheimer's disease.

In addition to its definitive pathological characteristics, neuritic plaques and neurofibrillary tangles, Alzheimer's disease (AD) brain exhibits regionally variable neuronal loss and synaptic dysfunction that are likely to underlie the symptomatic memory loss and language abnormalities. A number of mechanisms that could give rise to this localized damage have been proposed, amongst which excitotoxicity figures prominently. This is the process, well attested in experimental systems, whereby brain cells are excited to death by the pathophysiological action of the brain's most-abundant excitatory transmitter, glutamate. Glutamate transmission is mediated by a range of ionotropic and metabotropic receptors which, when activated, can lead to depolarization and increased intracellular Ca2+ ion concentration in the cells on which they are located. The action of glutamate is terminated by its removal from these receptor sites by transport into nearby cells, most commonly perisynaptic astrocytes. There it is converted to physiologically inert glutamine and shuttled back to excitatory nerve terminals. Malfunctions in components of the glutamate-glutamine cycle could result in a self-perpetuating neuronal death cascade mediated by glutamate. The approval by the FDA of an ionotropic glutamate receptor antagonist to treat late-stage AD has led to renewed interest in the contribution of altered glutamatergic neurotransmission to disease pathogenesis. This review encompasses those aspects of glutamate-glutamine cycling that are altered in AD.

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.

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.