Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9-10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence.

BACKGROUND: Air pollution is linked to neurodevelopmental delays, but its association with longitudinal changes in brain network development has yet to be investigated. We aimed to characterize the effect of PM2.5, O3, and NO2 exposure at ages 9-10 years on changes in functional connectivity (FC) over a 2-year follow-up period, with a focus on the salience (SN), frontoparietal (FPN), and default-mode (DMN) brain networks as well as the amygdala and hippocampus given their importance in emotional and cognitive functioning. METHODS: A sample of children (N = 9,497; with 1-2 scans each for a total of 13,824 scans; 45.6% with two brain scans) from the Adolescent Brain Cognitive Development (ABCD) Study® were included. Annual averages of pollutant concentrations were assigned to the child's primary residential address using an ensemble-based exposure modeling approach. Resting-state functional MRI was collected on 3T MRI scanners. First, developmental linear mixed-effect models were performed to characterize typical FC development within our sample. Next, single- and multi-pollutant linear mixed-effect models were constructed to examine the association between exposure and intra-network, inter-network, and subcortical-to-network FC change over time, adjusting for sex, race/ethnicity, income, parental education, handedness, scanner type, and motion. RESULTS: Developmental profiles of FC over the 2-year follow-up included intra-network integration within the DMN and FPN as well as inter-network integration between the SN-FPN; along with intra-network segregation in the SN as well as subcortical-to-network segregation more broadly. Higher PM2.5 exposure resulted in greater inter-network and subcortical-to-network FC over time. In contrast, higher O3 concentrations resulted in greater intra-network, but less subcortical-to-network FC over time. Lastly, higher NO2 exposure led to less inter-network and subcortical-to-network FC over the 2-year follow-up period. CONCLUSION: Taken together, PM2.5, O3, and NO2 exposure in childhood relate to distinct changes in patterns of network maturation over time. This is the first study to show outdoor ambient air pollution during childhood is linked to longitudinal changes in brain network connectivity development.

Barriers and facilitators of naloxone and safe injection facility interventions to reduce opioid drug-related deaths: A qualitative analysis.

BACKGROUND: Opioid drug-related deaths continue to be a significant public health concern in the Republic of Ireland (ROI) and Northern Ireland (NI). While both regions have implemented naloxone to reduce drug related deaths, there remains a gap in the implementation of a supervised injection facility (SIF). This study aimed to identify barriers and facilitators to implementing naloxone and a SIF to reduce opioid drug-related deaths in ROI and NI. METHODS: Semi-structured interviews (n=23) were conducted in ROI and NI with experts by experience (n=8), staff from low threshold services (n=9), and individuals involved in policy making (n= 6). Data were analyzed using coding reliability Thematic Analysis and were informed by the Risk Environmental Framework. RESULTS: The findings illustrated that stigma within the media, health centers, and the community was a significant barrier to naloxone distribution and SIF implementation. Policing and community intimidation were reported to hinder naloxone carriage in both the ROI and NI, while threats of paramilitary violence towards people who use drugs were unique to NI. Municipal government delays and policy maker apathy were reported to hinder SIF implementation in the ROI. Participants suggested peer-to-peer naloxone delivery and amending legislation to facilitate non-prescription naloxone would increase naloxone uptake. Participants recommended using webinars, Town Halls, and a Citizens' Assembly as tools to advocate for SIF implementation. CONCLUSION: Local and regional stigma reduction campaigns are needed in conjunction with policy changes to advance naloxone and a SIF. Tailoring stigma campaigns to incorporate the lived experience of people who use drugs, their family members, and the general community can aid in educating the public and change negative perceptions. This study highlights the need for ongoing efforts to reduce stigma and increase accessibility to evidence-based interventions to address opioid drug-related deaths in the ROI, NI, and internationally.

Air pollution and emotional behavior in adolescents across the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study examines how annual average PM2.5 and NO2 exposure at ages 9-10 years relates to internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at baseline and annually for two follow-up sessions for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Overall, the pollution effects moderated the main effects of age with higher levels of PM2.5 and NO2 leading to an even greater likelihood of having no behavioral problems (i.e., score of zero) with age over time, as well as fewer problems when problems are present as the child ages. Albeit this was on the order equal to or less than a 1-point change. Thus, one year of annual exposure at 9-10 years is linked with very small change in emotional behaviors in early adolescence, which may be of little clinical relevance.

Effect of Pharmacist Interventions on Hospital Readmissions for Home-Based Primary Care Veterans.

Background: Several studies indicate that when patients transition from one level of care to another, errors may occur. Pharmacists can play an integral role in the transitions of care process. At Michael E. DeBakey Veteran Affairs Medical Center, the Home-Based Primary Care (HBPC) service has implemented a streamlined hospital discharge plan to improve 30-day readmission rates after 1 year of HBPC enrollment. Methods: Our aim was to identify specific pharmacist interventions to improve the HBPC discharge process and ultimately, improve hospital readmission rates. A Plan-Do-Study-Act quality improvement project was initiated. We conducted a review of veterans enrolled in HBPC from October 2019 to March 2020. Results: Of 175 patients assessed postdischarge, a medication reconciliation was completed by an HBPC pharmacist in 118 (67.4%) patients. Of the 118 medication reconciliations completed, 92 (78%) interventions were made by HBPC pharmacists. During the 6-month study period, 30-day hospital readmission rates decreased from 19% to 13%. Conclusions: This study demonstrates several opportunities for interventions to lower readmission rates. Using the results from this study, education has been provided for the HBPC service and its readmission committee.

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK.

Objective: To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity. Design: General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases. Results: 325 subjects engaged in the programme and had sufficient data for analysis. Baseline characteristics were: age 47.8±12. 8 years; body mass index (BMI) 36.1±6.8 kg/m2; 79.1% female/20.9% male; 13.5% had type 2 diabetes. After 15±4 years weight had changed from 97.9±19 kg at baseline to 100±20.8 kg. 10 with diabetes at baseline were in remission at 3 months, but only two remained in remission at 5 years. 50 new cases of type 2 diabetes and 11 of impaired fasting glucose developed during follow-up. Only 5.9% who remained healthy at follow-up had maintained >10% body weight reduction. Neither diabetes incidence nor diabetes free survival were related to percentage body weight lost during VLCD. Only baseline BMI was related to development of new impaired fasting glucose or diabetes by 15 years (p=0.007). 37 subjects had a cardiovascular event. Age (p=0.000002) and degree of weight loss after VLCD (p=0.03) were significantly associated with subsequent vascular events. Conclusion: Long-term maintenance of weight loss after VLCD was rare in this single centre retrospective study 15 years later. Glucose intolerance developed in 21.4%. Lasting remission of type 2 diabetes or prevention of later glucose intolerance were not achieved. Vascular events were more frequent in those who lost most weight. Risk management during weight regain should be studied in future to assess potential for reduction in adverse cardiovascular outcomes.

How do naloxone-based interventions work to reduce overdose deaths: a realist review.

BACKGROUND: Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone; however, the role of context and mechanisms for its use has not been explored. This realist systematic review aims to identify a theory of how naloxone works based on the contexts and mechanisms that contribute to the success of the intervention for improved outcomes. METHODS: Pre-registered at PROSPERO, this realist review followed RAMESES standards of reporting. Keywords included 'naloxone' and ' opioid overdose'. All study designs were included. Data extraction using 55 relevant outputs based on realist logic produced evidence of two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory. RESULTS: Harm reduction and/or low threshold contexts provide a non-judgemental approach which support in-group norms of helping and empower the social identity of the trained and untrained bystander. This context also creates the conditions necessary for skills transfer and diffusion of the intervention into social networks. Stigma and negative attitudes held by first responders and stakeholders involved in the implementation process, such as police or GPs, can prohibit the bystander response by inducing fear in responding. This interferes with skills transfer, naloxone use and carriage of naloxone kits. CONCLUSIONS: The findings provide theoretically informed guidance regarding the harm reduction contexts that are essential for the successful implementation of naloxone-based interventions. Peer-to-peer models of training are helpful as it reinforces social identity and successful skills transfer between bystanders. Health systems may want to assess the prevalence of, and take steps to reduce opioid-related stigma with key stakeholders in contexts using a low threshold training approach to build an environment  to support positive naloxone outcomes. TRIAL REGISTRATION: PROSPERO 2019 CRD42019141003.

Associations between testosterone, estradiol, and androgen receptor genotype with amygdala subregions in adolescents.

Much is known about the development of the whole amygdala, but less is known about its structurally and functionally diverse subregions. One notable distinguishing feature is their wide range of androgen and estrogen receptor densities. Given the rise in pubertal hormones during adolescence, sex steroid levels as well as receptor sensitivity could influence age-related subregion volumes. Therefore, our goal was to evaluate the associations between the total amygdala and its subregion volumes in relation to sex hormones - estradiol and free testosterone (FT) - as a function of age and genetic differences in androgen receptor (AR) sensitivity in a sample of 297 adolescents (46% female). In males, we found small effects of FT-by-age interactions in the total amygdala, portions of the basolateral complex, and the cortical and medial nuclei (CMN), with the CMN effects being moderated by AR sensitivity. For females, small effects were seen with increased genetic AR sensitivity relating to smaller basolateral complexes. However, none of these small effects passed multiple comparisons. Future larger studies are necessary to replicate these small, yet possibly meaningful effects of FT-by-age associations and modulation by AR sensitivity on amygdala development to ultimately determine if they contribute to known sex differences in emotional neurodevelopment.

Microstructural properties within the amygdala and affiliated white matter tracts across adolescence.

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8-22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Implementing Health Care Quality Measures in Electronic Health Records: A Conceptual Model.

BACKGROUND/OBJECTIVES: There is significant literature on the development and validation of quality measures, but comparably less on their implementation into learning health systems. Electronic Health Records (EHRs) have made vast amounts of data available for quality improvement purposes. In this paper we describe a conceptual model for EHR implementation of quality measures. DESIGN: The model involves five steps: (1) select a measure; (2) define measure criteria; (3) validate criteria and measurement process; (4) improve recording of measure-related activity; and (5) engage quality improvement processes. The model was used to develop and implement a quality measure in the Home-Based Medical Care (HBMC) setting. SETTING: Harris Health House Call Program (HHHC) provides primary medical and palliative care for homebound patients in Houston. PARTICIPANTS: Four-hundred twenty-four primary care patients followed in the HHHC. MEASUREMENT: Completion rate of the 9-item Patient Health Questionnaire (PHQ-9) within the Electronic Health Record of newly enrolled HHHC patients. RESULTS: Use of the conceptual model to guide implementation of a quality measure of depression screening in a HMBC practice was successful. Additional components of early leadership and clinician buy-in were required, as well as strong relationships with IT to ease implementation and limit disruptions in clinicians' work-flow. CONCLUSION: This conceptual model was feasible for guiding implementation of a quality measure for depression care of HBMC patients, and it can guide broader implementation of EHR-based quality measures in the future.

Restructuring of amygdala subregion apportion across adolescence.

Total amygdala volumes develop in association with sex and puberty, and postmortem studies find neuronal numbers increase in a nuclei specific fashion across development. Thus, amygdala subregions and composition may evolve with age. Our goal was to examine if amygdala subregion absolute volumes and/or relative proportion varies as a function of age, sex, or puberty in a large sample of typically developing adolescents (N = 408, 43 % female, 10-17 years). Utilizing the in vivo CIT168 atlas, we quantified 9 subregions and implemented Generalized Additive Mixed Models to capture potential non-linear associations with age and pubertal status between sexes. Only males showed significant age associations with the basolateral ventral and paralaminar subdivision (BLVPL), central nucleus (CEN), and amygdala transition area (ATA). Again, only males showed relative differences in the proportion of the BLVPL, CEN, ATA, along with lateral (LA) and amygdalostriatal transition area (ASTA), with age. Using a best-fit modeling approach, age, and not puberty, was found to drive these associations. The results suggest that amygdala subregions show unique variations with age in males across adolescence. Future research is warranted to determine if our findings may contribute to sex differences in mental health that emerge across adolescence.

Supporting people who have eating and drinking difficulties.

Eating and drinking are essential for maintenance of nutrition and hydration, but are also important for pleasure and social interactions. The ability to eat and drink hinges on a complex and coordinated system, resulting in significant potential for things to go wrong.The Royal College of Physicians (RCP) has published updated guidance on how to support people who have eating and drinking difficulties, particularly towards the end of life.Decisions about nutrition and hydration and when to start, continue or stop treatment are some of the most challenging to make in medical practice. The newly updated guidance aims to support healthcare professionals to work together with patients, their families and carers to make decisions around nutrition and hydration that are in the best interests of the patient. It covers the factors affecting our ability to eat and drink, strategies to support oral nutrition and hydration, techniques of clinically-assisted nutrition and hydration, and the legal and ethical framework to guide decisions about giving and withholding treatment, emphasising the two key concepts of capacity and best interests.This article aims to provide an executive summary of the guidance.

The Roles of Physical Activity, Exercise, and Fitness in Promoting Resilience During Adolescence: Effects on Mental Well-Being and Brain Development.

Adolescence is a critical yet vulnerable period for developing behaviors important for mental well-being. The existing literature suggests that physical activity (PA), exercise, and aerobic fitness promote well-being and reduce risk of mental health problems. In this review, we focus on PA, exercise, and fitness as modifiable resilience factors that may help promote self-regulation via strengthening of top-down control of bottom-up processes in the brain, thereby acting as a buffer against mental health problems during this period of vulnerability. First, we briefly review the link between PA, exercise, and aerobic fitness with mental well-being and reduced mental health problems in adolescence. Then we present how impairments in self-regulation, which involves top-down control to modulate bottom-up processes, are common across a wide range of mental health disorders. Finally, we use the extant neuroimaging literature to highlight how neural systems underlying top-down control continue to develop across adolescence, and propose that PA, exercise, and aerobic fitness may facilitate resilience through strengthening individual brain regions as well as large-scale neural circuits to improve emotional and behavioral regulation. Future neuroimaging studies assessing the effects of PA, exercise, and aerobic fitness at various developmental stages in each sex and studies considering the characteristics (e.g., frequency, intensity, type) and social context of PA and exercise are vital to better understand both macro- and microscale mechanisms by which these behaviors and attributes may facilitate mental health resilience during adolescent development.

Prefrontal Cortex and Amygdala Subregion Morphology Are Associated With Obesity and Dietary Self-control in Children and Adolescents.

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex (PFC; involved in cognitive control) and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8-22 years (17.35 ± 4.76 years, 51% female, 56% were overweight or obese) participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant's self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary "self-control" was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions (p < 0.05, corrected for multiple comparisons). We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala (p = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity.

Framing the Clinical Encounter: Shared Decision-Making, Mammography Screening, and Decision Satisfaction.

The study examines whether physicians' framing of clinical interactions is related to patient shared decision-making (SDM) satisfaction when using a clinical decision support tool (CDST) concerning mammographic screening. To answer this question, we combined (a) system log data from a CDST, (b) content coding of the physicians' message framing while using the CDST, and (c) a post-visit patient survey to assess SDM satisfaction concerning screening mammography. Results suggest that two types of message frames - consequence frames and numerical frames - moderated the relationship of the CDST on SDM satisfaction. When the CDST displayed low risk of breast cancer for a patient, physicians were able to improve the cognitive aspects of SDM satisfaction by framing the consequences of mammography screening in positive terms. However, when the physician delivered the numerical information in relative, rather than absolute terms, the patient's SDM satisfaction was reduced. Our study advances previous message framing effect research in health communication from experimental settings to clinical encounters. It also discusses the importance of delivering risk-congruent frames in clinical settings.

Decreasing Heart Failure Readmissions Among Older Patients With Cognitive Impairment by Engaging Caregivers.

BACKGROUND: Cognitive impairment is common in older patients with heart failure (HF), leading to higher 30-day readmission rates than those without cognitive impairment. OBJECTIVES: The aim of this study was to determine whether increased readmissions in older adults with cognitive impairment are related to HF severity and whether readmissions can be modified by caregiver inclusion in nursing discharge education. METHODS: This study used prospective quality improvement program of cognitive testing and inclusion of caregivers in discharge education with chart review. Two hundred thirty-two patients older than 70 years admitted with HF were screened for cognitive impairment using the Mini-Cog; if score was less than 4, nurses were asked to include caregivers in education on 2 cardiovascular units with an enhanced discharge program. Individuals with ventricular assist device, transplant, or hospice were excluded. Measurements include Mini-Cog score, 30-day readmissions, readmission risk score, ejection fraction, brain natriuretic peptide, and medical comorbidities. RESULTS: Readmission Risk Scores for HF did not correlate with Mini-Cog scores, but admission brain natriuretic peptide levels were less abnormal in those with better Mini-Cog scores. Only for patients with cognitive impairment, involving caregivers in discharge teaching given by registered and advanced practice nurses was associated with decreased 30-day readmissions from 35% to 16% (P = .01). Readmission rates without/with cognitive impairment were 14.1% and 23.8%, respectively (P = .09). Abnormal Mini-Cog screen was associated with a significantly increased risk of 30-day readmission (odds ratio, 2.23; 95% confidence interval, 1.06-4.68; P = .03), whereas nurse documentation of education with family was associated with a significantly decreased risk of 30-day readmission (odds ratio, 0.46; 95% confidence interval, 0.24-0.90; P = .02). CONCLUSIONS: Involving caregivers in discharge education significantly reduced 30-day readmission rates for patients with HF and cognitive impairment. The Readmission Risk Score was similar between patients older than 70 years with and without cognitive impairment. We have hypothesis-generating evidence that identification of cognitive impairment and targeted caregiver engagement by nurses may be critical in the reduction of readmission rates for older patients with HF.

Using a Logic Model to Design and Evaluate a Quality Improvement Leadership Course.

Strong leadership is an essential factor in the success of quality improvement (QI) initiatives that generate and sustain improvements in patient outcomes. Notably, there is a rising need for frontline clinicians, who are often charged with leading QI efforts, to receive training in blended QI and leadership methods and skills. The Leading Healthcare Improvement (LHI) course is a longitudinal leadership course embedded within the Department of Veterans Affairs Quality Scholars (VAQS) program, a multisite interprofessional QI fellowship program. The LHI course was developed to provide frontline clinicians who are emerging QI leaders with the skills to lead and advance improvement efforts at their institutions. It consists of eight 60-minute online sessions and was implemented and delivered to a cohort of interprofessional fellows at 9 sites during the 2017-2018 academic year.This article describes the use of a logic model as a framework to guide the planning, implementation, and evaluation of the LHI course. The authors developed 5 logic model components: inputs, activities, outputs, short-term outcomes, and long-term outcomes. They defined the short-term outcomes using feedback from fellows and an evaluation of the fellows' abstract submissions to the VAQS Summer Institute. Submissions were reviewed to identify how fellows applied the LHI course concepts to QI projects at their respective sites. The authors also collected preliminary impact data from fellows to determine long-term outcomes.Finally, they used the logic model to inform changes to the LHI course based on the evaluation data they collected and developed plans to measure the impact of the course on learners, patients, and the health care system. The authors conclude with lessons learned to guide others who are implementing similar QI efforts.

Outdoor Air Pollution and Brain Structure and Function From Across Childhood to Young Adulthood: A Methodological Review of Brain MRI Studies.

Outdoor air pollution has been recognized as a novel environmental neurotoxin. Studies have begun to use brain Magnetic Resonance Imaging (MRI) to investigate how air pollution may adversely impact developing brains. A systematic review was conducted to evaluate and synthesize the reported evidence from MRI studies on how early-life exposure to outdoor air pollution affects neurodevelopment. Using PubMed and Web of Knowledge, we conducted a systematic search, followed by structural review of original articles with individual-level exposure data and that met other inclusion criteria. Six studies were identified, each sampled from 3 cohorts of children in Spain, The Netherlands, and the United States. All studies included a one-time assessment of brain MRI when children were 6-12 years old. Air pollutants from traffic and/or regional sources, including polycyclic aromatic hydrocarbons (PAHs), nitrogen dioxide, elemental carbon, particulate matter (<2.5 or <10 µm), and copper, were estimated prenatally (n = 1), during childhood (n = 3), or both (n = 2), using personal monitoring and urinary biomarkers (n = 1), air sampling at schools (n = 4), or a land-use regression (LUR) modeling based on residences (n = 2). Associations between exposure and brain were noted, including: smaller white matter surface area (n = 1) and microstructure (n = 1); region-specific patterns of cortical thinness (n = 1) and smaller volumes and/or less density within the caudate (n = 3); altered resting-state functional connectivity (n = 2) and brain activity to sensory stimuli (n = 1). Preliminary findings suggest that outdoor air pollutants may impact MRI brain structure and function, but limitations highlight that the design of future air pollution-neuroimaging studies needs to incorporate a developmental neurosciences perspective, considering the exposure timing, age of study population, and the most appropriate neurodevelopmental milestones.

A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth.

The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR's functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1ß and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPß). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.

What is the most ecologically-meaningful metric of nitrogen deposition?

Nitrogen (N) deposition poses a severe risk to global terrestrial ecosystems, and managing this threat is an important focus for air pollution science and policy. To understand and manage the impacts of N deposition, we need metrics which accurately reflect N deposition pressure on the environment, and are responsive to changes in both N deposition and its impacts over time. In the UK, the metric typically used is a measure of total N deposition over 1-3 years, despite evidence that N accumulates in many ecosystems and impacts from low-level exposure can take considerable time to develop. Improvements in N deposition modelling now allow the development of metrics which incorporate the long-term history of pollution, as well as current exposure. Here we test the potential of alternative N deposition metrics to explain vegetation compositional variability in British semi-natural habitats. We assembled 36 individual datasets representing 48,332 occurrence records in 5479 quadrats from 1683 sites, and used redundancy analyses to test the explanatory power of 33 alternative N metrics based on national pollutant deposition models. We find convincing evidence for N deposition impacts across datasets and habitats, even when accounting for other large-scale drivers of vegetation change. Metrics that incorporate long-term N deposition trajectories consistently explain greater compositional variance than 1-3 year N deposition. There is considerable variability in results across habitats and between similar metrics, but overall we propose that a thirty-year moving window of cumulative deposition is optimal to represent impacts on plant communities for application in science, policy and management.