Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater than grade 3. Most anti-MM activity occurred within 2-4 weeks of FHVH-T infusion as shown by decreases in the rapidly changing MM markers serum free light chains, urine light chains, and bone marrow plasma cells. Blood CAR+ cell levels peaked during the time that MM elimination was occurring, between 7 and 15 days after FHVH-T infusion. C-C chemokine receptor type 7 (CCR7) expression on infusion CD4+ FHVH-T correlated with peak blood FHVH-T levels. Single-cell RNA sequencing revealed a shift toward more differentiated FHVH-T after infusion. Anti-CAR antibody responses were detected in 4 of 12 patients assessed. FHVH-T has powerful, rapid, and durable anti-MM activity.

Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Associations between prenatal and early-life air pollution exposure and lung function in young children: Exploring influential windows of exposure on lung development.

BACKGROUND: Evidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood. OBJECTIVES: We evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6-9, in an effort to identify potentially influential windows of exposure for lung development. METHODS: Our study population consisted of 222 children aged 6-9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates. RESULTS: PM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 µg/m3) to the median observed exposure (12.69 µg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): -0.82, -0.03) and 0.38 L lower FEV1 (95% CI: -0.75, -0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null. CONCLUSIONS: Our findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

Traffic-related air pollution is associated with glucose dysregulation, blood pressure, and oxidative stress in children.

BACKGROUND: Metabolic syndrome increases the risk of cardiovascular disease in adults. Antecedents likely begin in childhood and whether childhood exposure to air pollution plays a contributory role is not well understood. OBJECTIVES: To assess whether children's exposure to air pollution is associated with markers of risk for metabolic syndrome and oxidative stress, a hypothesized mediator of air pollution-related health effects. METHODS: We studied 299 children (ages 6-8) living in the Fresno, CA area. At a study center visit, questionnaire and biomarker data were collected. Outcomes included hemoglobin A1c (HbA1c), urinary 8-isoprostane, systolic blood pressure (SBP), and BMI. Individual-level exposure estimates for a set of four pollutants that are constituents of traffic-related air pollution (TRAP) - the sum of 4-, 5-, and 6-ring polycyclic aromatic hydrocarbon compounds (PAH456), NO2, elemental carbon, and fine particulate matter (PM2.5) - were modeled at the primary residential location for 1-day lag, and 1-week, 1-month, 3-month, 6-month, and 1-year averages prior to each participant's visit date. Generalized additive models were used to estimate associations between each air pollutant exposure and outcome. RESULTS: The study population was 53% male, 80% Latinx, 11% Black and largely low-income (6% were White and 3% were Asian/Pacific Islander). HbA1c percentage was associated with longer-term increases in TRAP; for example a 4.42 ng/m3 increase in 6-month average PAH456 was associated with a 0.07% increase (95% CI: 0.01, 0.14) and a 3.62 µg/m3 increase in 6-month average PM2.5 was associated with a 0.06% increase (95% CI: 0.01, 0.10). The influence of air pollutants on blood pressure was strongest at 3 months; for example, a 6.2 ppb increase in 3-month average NO2 was associated with a 9.4 mmHg increase in SBP (95% CI: 2.8, 15.9). TRAP concentrations were not significantly associated with anthropometric or adipokine measures. Short-term TRAP exposure averages were significantly associated with creatinine-adjusted urinary 8-isoprostane. DISCUSSION: Our results suggest that both short- and longer-term estimated individual-level outdoor residential exposures to several traffic-related air pollutants, including ambient PAHs, are associated with biomarkers of risk for metabolic syndrome and oxidative stress in children.

Impact of an integrated community-based model of care for older people with complex conditions on hospital emergency presentations and admissions: a step-wedged cluster randomized trial.

BACKGROUND: Health systems must reorient towards preventative and co-ordinated care to reduce hospital demand and achieve positive and fiscally responsible outcomes for older persons with complex needs. Integrated care models can improve outcomes by aligning primary practice with the specialist health and social services required to manage complex needs. This paper describes the impact of a community-facing program that integrates care at the primary-secondary interface on the rate of Emergency Department (ED) presentation and hospital admissions among older people with complex needs. METHODS: The Older Persons Enablement and Rehabilitation for Complex Health Conditions (OPEN ARCH) study is a multicentre randomised controlled trial with a stepped wedge cluster design. General practitioners (GPs; n = 14) in primary practice within the Cairns region are considered 'clusters' each comprising a mixed number of participants. 80 community-dwelling persons over 70 years of age if non-Indigenous and over 50 years of age if Indigenous were included at baseline with no new participants added during the study. Clusters were randomly assigned to one of three steps that represent the time at which they would commence the OPEN ARCH intervention, and the subsequent intervention duration (3, 6, or 9 months). Each participant was its own control. GPs and participants were not blinded. The primary outcomes were ED presentations and hospital admissions. Data were collected from Queensland Health Casemix data and analysed with multilevel mixed-effects Poisson regression modelling to estimate the effectiveness of the OPEN ARCH intervention. Data were analysed at the cluster and participant levels. RESULTS: Five clusters were randomised to steps 1 and 2, and 4 clusters randomised to step 3. All clusters (n = 14) completed the trial accounting for 80 participants. An effect size of 9% in service use (95% CI) was expected. The OPEN ARCH intervention was found to not make a statistically significant difference to ED presentations or admissions. However, a stabilising of ED presentations and a trend toward lower hospitalisation rates over time was observed. CONCLUSIONS: While this study detected no statistically significant change in ED presentations or hospital admissions, a plateauing of ED presentation and admission rates is a clinically significant finding for older persons with complex needs. Multi-sectoral integrated programs of care require an adequate preparation period and sufficient duration of intervention for effectiveness to be measured. TRIAL REGISTRATION: The OPEN ARCH study received ethical approval from the Far North Queensland Human Research Ethics Committee, HREC/17/QCH/104-1174 and is registered on the Australian and New Zealand Trials Registry, ACTRN12617000198325p .

Investigation burden for patients with fibrotic interstitial lung disease at the end of life.

Fibrotic interstitial lung disease (f-ILD) has a guarded prognosis, and the goal of therapy in advanced-stage disease should be symptom-based. Despite this, patients may still undergo burdensome investigation at the end of life. A retrospective audit was performed on 67 patients who died from f-ILD at the Royal Melbourne and Austin Hospitals between 2012 and 2016. Increased investigation burden was associated with lack of outpatient palliative care referral and documented advance care plan, and admission to a high-dependency unit. Eighteen per cent of patients underwent ongoing investigations after the institution of comfort care. These findings highlight the unmet end-of-life care needs of people with f-ILD.

A Case Report of Pediatric Paraneoplastic Dysautonomia.

We present the case of a 16-year-old girl who presented with severe refractory orthostatic hypotension secondary to pandysautonomia. Initially, she was treated for Guillain-Barré syndrome given clinical symptoms and increased protein on cerebrospinal fluid, but the severity of symptoms and lack of response to intravenous immunoglobulin prompted further evaluation for an autoimmune etiology. She was ultimately diagnosed with paraneoplastic neuropathy secondary to Hodgkin lymphoma. Paraneoplastic neurologic phenomena are rare, occurring in just 0.01% of cancers, and prompt recognition is crucial for initiating appropriate therapy. Rapid progression of severe disabling symptoms should raise suspicion for an underlying malignancy. The patient had limited response to splanchnic vasoconstrictors in addition to α-agonists, anticholinergics, and mineralocorticoids until initiation of modified Hodgkin lymphoma directed chemotherapy plus rituximab.

The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission.

BACKGROUND: The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016. OBJECTIVE: Among thunderstorm-affected patients presenting to emergency rooms (ERs), we investigated risk factors predicting severe attacks requiring admission to hospital. METHODS: Thunderstorm-affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed. RESULTS: We interviewed 1435/2248 (64%) of thunderstorm-affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [aOR] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission (aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non-Asian patients (aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia (OR = 5.42, 95% CI 1.56, 18.83). CONCLUSIONS: In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions.

Probing alkenoxy radical electronic structure using anion PEI spectroscopy.

Photoelectron imaging spectra of three alkenoxide radical anions (3-buten-1-oxide, 3-buten-2-oxide, and 2-propenoxide) are presented and analyzed with supporting results of density functional theory calculations. In all spectra, intense detachment features are observed at approximately 2 eV electron binding energy, which is similar to the electron affinities of saturated neutral alkoxy radicals [Ramond et al., J. Chem. Phys. 112, 1158 (2000)]. Photoelectron angular distributions suggest the presence of several overlapping transitions which are assigned to the X̃ and à states of multiple energetically competitive conformers. The term energy of the à state of the 2-propenoxy radical, 0.17 eV, is higher than that of 3-buten-2-oxy (0.13 eV) and 3-buten-1-oxy (0.05 eV) radicals. Comparing the butenoxy radicals, we infer that stronger interactions between the non-bonding O 2p orbitals and the π bond increase the splitting between the ground and the first excited state in the 3-buten-2-oxy radical relative to the 3-buten-1-oxy radical.

Are we there yet? Exploring the journey to quality stroke care for Aboriginal and Torres Strait Islander peoples in rural and remote Queensland.

INTRODUCTION: The burden of stroke for Aboriginal and Torres Strait Islander peoples in Australia is significant. The National Stroke Foundation has identified that Aboriginal and Torres Strait Islander people are more likely to have a stroke at a younger age than the non-Indigenous population and are twice as likely for stroke to result in death, and that those Aboriginal and Torres Strait Islander people living in rural and remote areas are less likely to have access to an acute stroke unit. The only acute stroke unit in Far North Queensland treats six times more Aboriginal and Torres Strait Islander patients than the Queensland average, a large proportion of whom reside in the rural and remote communities of the Cape and Torres Strait. This article describes part of the qualitative phase of a project titled 'Culturally appropriate stroke services for Aboriginal and Torres Strait Islander people', received Closing the Gap funding to identify the needs of Aboriginal and Torres Strait Islander stroke survivors in Far North Queensland and establish a model of care that is responsive to these needs. METHOD: Data were collected from 24 stroke survivors, 10 carers and 70 stakeholders through surveys. The surveys incorporated open-ended questions and were administered through face to face interviews with participants from across 18 diverse Aboriginal and Torres Strait Islander communities within Far North Queensland. Guided by the principles of thematic analysis the data were coded, categories created and themes and subthemes identified. RESULTS: This study emphasises the need for an inclusive coordinated and culturally responsive approach to Aboriginal and Torres Strait Islander stroke care that values the role of the client, their family and community. The Aboriginal and Torres Strait Islander liaison officer has a pivotal role within the multidisciplinary team. Resources specific to the language, literacy and cultural needs of Aboriginal and Torres Strait Islander stroke survivors are required as is advocacy for the availability and use of Aboriginal and Torres Strait Islander language interpreters. Aboriginal and Torres Strait Islander stroke survivors have limited opportunity to fulfil their rehabilitation potential after hospital discharge. CONCLUSION: An integrated patient centred model of care that spans the care continuum and places value on an extended role for the Aboriginal and Torres Strait Islander health worker workforce is indicated, as is an increased utilisation of allied health and specialist follow-up close to home.

Bolstering Community Cooperation in Ebola Resurgence Protocols: Combining Field Blood Draw and Point-of-Care Diagnosis.

Alison Galvani and colleagues describe a community-based protocol to improve cooperation with Ebola testing as well as contact tracing, quarantining, and treatment.

O2-·[Polar VOC] Complexes: H-Bonding versus Charge-Dipole Interactions, and the Noninnocence of Formaldehyde.

Anion photoelectron imaging was used to measure the photodetachment spectra of molecular complexes formed between O2- and a range of atmospherically relevant polar molecules, including species with a carbonyl group (acetone, formaldehyde) and alcohols (ethanol, propenol, butenol). Experimental spectra are analyzed using a combination of Franck-Condon simulations and electronic structure calculations. Strong charge-dipole interactions and H-bonding stabilize the complex anions relative to the neutrals, resulting in a ca. 1 eV increase in electron binding energy relative to bare O2-, an effect more pronounced in complexes with H-bonding. In addition, broken degeneracy of the O2-local πg orbitals in the complexes results in the stabilization of the low-lying excited O2 (a 1Δg)·[polar VOC] state relative to the ground O2 (X 3Σg-)·[polar VOC] state when compared to bare O2. The spectra of the O2-·[polar VOC] complexes exhibit less pronounced laser photoelectron angular distribution (PADs). The spectrum of O2-·formaldehyde is unique in terms of both spectral profile and PAD. On the basis of these experimental results in addition to computational results, the complex anion cannot be described as a distinct O2- anion partnered with an innocent solvent molecule; the molecules are more strongly coupled through charge delocalization. Overall, the results underscore how the symmetry of the O2 πg orbitals is broken by different polar partners, which may have implications for atmospheric photochemistry and models of solar radiation absorption that include collision-induced absorption.

Lung function in woodsmoke-exposed Guatemalan children following a chimney stove intervention.

RATIONALE: Household air pollution (HAP) from solid fuel combustion is a major contributor to the global burden of disease, with considerable impact from respiratory infections in children. The impact of HAP on lung function is unknown. OBJECTIVES: The Childhood Exposure to Respirable Particulate Matter (CRECER) prospective cohort study followed Guatemalan children who participated in the Randomised Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) trial of a chimney stove intervention to determine the effect of early childhood HAP exposure on growth of lung function. METHODS: RESPIRE households with pregnant women or infant children were randomised to receive a chimney stove at the beginning or at the end of the 18-month trial. During CRECER, a subset of these children, as well as children from households with newly installed stoves, were followed with spirometry beginning at age 5. Biomass smoke exposure was measured using personal carbon monoxide tubes. Two-stage regression models were employed to analyse associations with lung function growth. MEASUREMENTS AND MAIN RESULTS: Longitudinal peak expiratory flow (PEF) and FEV1 data were available for 443 and 437 children, respectively, aged 5-8 (mean follow-up 1.3 years). Decreases in PEF growth of 173 mL/min/year (95% CI -341 to -7) and FEV1 of 44 mL/year (95% CI -91 to 4) were observed with stove installation at 18 months compared with stove installation at birth in analyses adjusted for multiple covariates. No statistically significant associations were observed between personal HAP exposure and lung function. CONCLUSIONS: A significant decrease in PEF growth and a large non-significant decrease in FEV1 growth were observed with later stove installation. Additional studies including longer follow-up and cleaner stoves or fuels are needed.

Photoelectron Imaging Spectra of O2-·VOC and O4-·VOC Complexes.

The anion photoelectron imaging spectra of O2-·VOC and O4-·VOC (VOC = hexane, isoprene, benzene, and benzene-d6) complexes measured using 3.49 eV photon energy, along with the results of ab initio and density functional theory results are reported and analyzed. Photodetachment of these anionic complexes accesses neutrals that model collision complexes, offering a probe of the effects of symmetry-breaking collision events on the electronic structure of normally transparent neutral molecules. The energies of O2-·VOC spectral features compared to the bare O2- indicate that photodetachment of the anion accesses a modestly repulsive region of the O2-VOC potential energy surface, with subtle VOC dependence on the relative energies of the O2 (X 3Σg-)·VOC ground state and O2 (a 1Δg)·VOC excited state. In contrast, a significantly higher intensity of the transition to the O2 (a 1Δg)·VOC excited state relative to the O2 (X 3Σg-)·VOC ground state is observed for VOC = benzene, with a less pronounced effect observed for VOC = isoprene. Similar spectral effects are observed in the O4-·benzene and O4-·isoprene PE spectra. Several explanations are considered, with involvement of a temporary anion state emerging as the most plausible.

Differential respiratory health effects from the 2008 northern California wildfires: A spatiotemporal approach.

We investigated health effects associated with fine particulate matter during a long-lived, large wildfire complex in northern California in the summer of 2008. We estimated exposure to PM2.5 for each day using an exposure prediction model created through data-adaptive machine learning methods from a large set of spatiotemporal data sets. We then used Poisson generalized estimating equations to calculate the effect of exposure to 24-hour average PM2.5 on cardiovascular and respiratory hospitalizations and ED visits. We further assessed effect modification by sex, age, and area-level socioeconomic status (SES). We observed a linear increase in risk for asthma hospitalizations (RR=1.07, 95% CI=(1.05, 1.10) per 5µg/m(3) increase) and asthma ED visits (RR=1.06, 95% CI=(1.05, 1.07) per 5µg/m(3) increase) with increasing PM2.5 during the wildfires. ED visits for chronic obstructive pulmonary disease (COPD) were associated with PM2.5 during the fires (RR=1.02 (95% CI=(1.01, 1.04) per 5µg/m(3) increase) and this effect was significantly different from that found before the fires but not after. We did not find consistent effects of wildfire smoke on other health outcomes. The effect of PM2.5 during the wildfire period was more pronounced in women compared to men and in adults, ages 20-64, compared to children and adults 65 or older. We also found some effect modification by area-level median income for respiratory ED visits during the wildfires, with the highest effects observed in the ZIP codes with the lowest median income. Using a novel spatiotemporal exposure model, we found some evidence of differential susceptibility to exposure to wildfire smoke.

Underrecognition of Dengue during 2013 Epidemic in Luanda, Angola.

During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic test-positive cases were reported to the Ministry of Health. To better understand the magnitude of the epidemic and identify risk factors for dengue virus (DENV) infection, we conducted cluster surveys around households of case-patients and randomly selected households 6 weeks after the peak of the epidemic. Of 173 case cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247 random cluster participants, 25 (10%) had evidence of recent DENV infection. Of 13 recently infected participants who had a recent febrile illness, 7 (54%) had sought medical care, and 1 (14%) was hospitalized with symptoms consistent with severe dengue; however, none received a diagnosis of dengue. Behavior associated with protection from DENV infection included recent use of mosquito repellent or a bed net. These findings suggest that the 2013 dengue epidemic was larger than indicated by passive surveillance data.

Photoelectron imaging and photodissociation of ozonide in O3(-)⋠(O2)n (n = 1-4) clusters.

The photoelectron images of O3 (-) and O3 (-) ⋅ (O2)n (n = 1-4) have been measured using 3.49 eV photon energy. The spectra exhibit several processes, including direct photodetachment and photodissociation with photodetachment of O(-) photofragments. Several spectra also exhibit autodetachment of vibrationally excited O2 (-) photofragments. Comparison of the bare O3 (-) photoelectron spectra to that of the complexes shows that the O3 (-) core is preserved upon clustering with several O2 molecules, though subtle changes in the Franck-Condon profile of the ground state photodetachment transition suggest some charge transfer from O3 (-) to the O2 molecules. The electron affinities of the complexes increase by less than 0.1 eV with each additional O2 molecule, which is comparable to the corresponding binding energy [K. Hiraoka, Chem. Phys. 125, 439-444 (1988)]. The relative intensity of the photofragment O(-) detachment signal to the O3 (-) ⋅ (O2)n direct detachment signal increases with cluster size. O2 (-) autodetachment signal is only observed in the O3 (-), O3 (-) ⋅ (O2)3, and O3 (-) ⋅ (O2)4 spectra, suggesting that the energy of the dissociative state also varies with the number of O2 molecules present in the cluster.

Diurnal temperature range and short-term mortality in large US communities.

Research has shown that diurnal temperature range (DTR) is significantly associated with mortality and morbidity in regions of Asia; however, few studies have been conducted in other regions such as North America. Thus, we examined DTR effects on mortality in the USA. We used mortality and environmental data from the National Morbidity Mortality Air Pollution Study (NMMAPS). The data are daily mortality, air pollution, and temperature statistics from 95 large US communities collected between 1987 and 2000. To assess community-specific DTR effects on mortality, we used Poisson generalized linear models allowing for over-dispersion. After assessing community-specific DTR effects on mortality, we estimated region- and age-specific effects of DTR using two-level normal independent sampling estimation. We found a significant increase of 0.27 % [95 % confidence intervals (CI), 0.24-0.30 %] in nonaccidental mortality across 95 communities in the USA associated with a 1 °C increase in DTR, controlling for apparent temperature, day of the week, and time trend. This overall effect was driven mainly by effects of DTR on cardiovascular and respiratory mortality in the elderly: Mortality in the above 65 age group increased by 0.39 % (95 % CI, 0.33-0.44 %) and 0.33 % (95 % CI, 0.22-0.44 %), respectively. We found some evidence of regional differences in the effects of DTR on nonaccidental mortality with the highest effects in Southern California [0.31 % (95 % CI, 0.21-0.42 %)] and smallest effects in the Northwest and Upper Midwest regions [0.22 % (95 % CI, 0.11-0.33 %) and 0.22 % (95 % CI, 0.07-0.37 %), respectively]. These results indicate a statistically significant association between DTR and mortality on average for 95 large US communities. The findings indicate that DTR impacts on nonaccidental and cardiovascular-related mortality in most US regions and the elderly population was most vulnerable to the effects of DTR.

Developing small-area predictions for smoking and obesity prevalence in the United States for use in Environmental Public Health Tracking.

BACKGROUND: Globally and in the United States, smoking and obesity are leading causes of death and disability. Reliable estimates of prevalence for these risk factors are often missing variables in public health surveillance programs. This may limit the capacity of public health surveillance to target interventions or to assess associations between other environmental risk factors (e.g., air pollution) and health because smoking and obesity are often important confounders. OBJECTIVES: To generate prevalence estimates of smoking and obesity rates over small areas for the United States (i.e., at the ZIP code and census tract levels). METHODS: We predicted smoking and obesity prevalence using a combined approach first using a lasso-based variable selection procedure followed by a two-level random effects regression with a Poisson link clustered on state and county. We used data from the Behavioral Risk Factor Surveillance System (BRFSS) from 1991 to 2010 to estimate the model. We used 10-fold cross-validated mean squared errors and the variance of the residuals to test our model. To downscale the estimates we combined the prediction equations with 1990 and 2000 U.S. Census data for each of the four five-year time periods in this time range at the ZIP code and census tract levels. Several sensitivity analyses were conducted using models that included only basic terms, that accounted for spatial autocorrelation, and used Generalized Linear Models that did not include random effects. RESULTS: The two-level random effects model produced improved estimates compared to the fixed effects-only models. Estimates were particularly improved for the two-thirds of the conterminous U.S. where BRFSS data were available to estimate the county level random effects. We downscaled the smoking and obesity rate predictions to derive ZIP code and census tract estimates. CONCLUSIONS: To our knowledge these smoking and obesity predictions are the first to be developed for the entire conterminous U.S. for census tracts and ZIP codes. Our estimates could have significant utility for public health surveillance.