Association of Gaseous Ambient Air Pollution and Dementia-Related Neuroimaging Markers in the ARIC Cohort, Comparing Exposure Estimation Methods and Confounding by Study Site.

BACKGROUND: Evidence linking gaseous air pollution to late-life brain health is mixed. OBJECTIVE: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. METHODS: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (NO2), nitrogen oxides (NOx), and 8- and 24-h ozone (O3) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. RESULTS: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher NO2 and NOx and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. DISCUSSION: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, NOx, and NO2 and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906.

A comparison of PM2.5 exposure estimates from different estimation methods and their associations with cognitive testing and brain MRI outcomes.

BACKGROUND: Reported associations between particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity. OBJECTIVES: To assess agreement between PM2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM2.5 and cognitive or MRI outcomes. METHODS: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors. RESULTS: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM2.5-cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors. DISCUSSION: PM2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health.

Influence of Four Veterinary Antibiotics on Constructed Treatment Wetland Nitrogen Transformation.

The use of wetlands as a treatment approach for nitrogen in runoff is a common practice in agroecosystems. However, nitrate is not the sole constituent present in agricultural runoff and other biologically active contaminants have the potential to affect nitrate removal efficiency. In this study, the impacts of the combined effects of four common veterinary antibiotics (chlortetracycline, sulfamethazine, lincomycin, monensin) on nitrate-N treatment efficiency in saturated sediments and wetlands were evaluated in a coupled microcosm/mesocosm scale experiment. Veterinary antibiotics were hypothesized to significantly impact nitrogen speciation (e.g., nitrate and ammonium) and nitrogen uptake and transformation processes (e.g., plant uptake and denitrification) within the wetland ecosystems. To test this hypothesis, the coupled study had three objectives: 1. assess veterinary antibiotic impact on nitrogen cycle processes in wetland sediments using microcosm incubations, 2. measure nitrate-N reduction in water of floating treatment wetland systems over time following the introduction of veterinary antibiotic residues, and 3. identify the fate of veterinary antibiotics in floating treatment wetlands using mesocosms. Microcosms containing added mixtures of the veterinary antibiotics had little to no effect at lower concentrations but stimulated denitrification potential rates at higher concentrations. Based on observed changes in the nitrogen loss in the microcosm experiments, floating treatment wetland mesocosms were enriched with 1000 µg L-1 of the antibiotic mixture. Rates of nitrate-N loss observed in mesocosms with the veterinary antibiotic enrichment were consistent with the microcosm experiments in that denitrification was not inhibited, even at the high dosage. In the mesocosm experiments, average nitrate-N removal rates were not found to be impacted by the veterinary antibiotics. Further, veterinary antibiotics were primarily found in the roots of the floating treatment wetland biomass, accumulating approximately 190 mg m-2 of the antibiotic mixture. These findings provide new insight into the impact that veterinary antibiotic mixtures may have on nutrient management strategies for large-scale agricultural operations and the potential for veterinary antibiotic removal in these wetlands.

Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC-HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel.

Analysis was conducted to compare levodopa/carbidopa pharmacokinetics and drug-related material in plasma of healthy participants after receiving a continuous infusion of Levodopa/Carbidopa Intestinal Gel (LCIG) to a continuous subcutaneous infusion of foslevodopa/foscarbidopa. Study samples were from a randomized, open-label, 2-period crossover study in 20 healthy participants. Participants received either 24-h foslevodopa/foscarbidopa SC infusion to the abdomen or LCIG delivered for 24 h to the jejunum through a nasogastric tube with jejunal extension. Serial blood samples were collected for PK. Comparability of the LD PK parameters between the two treatment regimens was determined. Selected plasma samples were pooled per treatment group and per time point for metabolite profiling. LC-MSn was performed using high-resolution mass spectrometry to identify drug-related material across the dosing regimens and time points. The LD PK parameter central values and 90% confidence intervals following the foslevodopa/foscarbidopa subcutaneous infusion were between 0.8 and 1.25 relative to the LCIG infusion. With LCIG administration, LD, CD, 3-OMD, DHPA, DOPAC, and vanillacetic acid were identified in plasma at early and late time points (0.75 and 24 h); the metabolic profile after administration of foslevodopa/foscarbidopa demonstrated the same drug-related compounds with the exception of the administered foslevodopa. 3-OMD and vanillacetic acid levels increased over time in both treatment regimens. Relative quantification of LC-MS peak areas showed no major differences in the metabolite profiles. These results indicate that neither the addition of monophosphate prodrug moieties nor SC administration affects the circulating metabolite profile of foslevodopa/foscarbidopa compared to LCIG.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

High accuracy of positioning custom triflange acetabular components in tumour and total hip arthroplasty revision surgery.

Aims: Custom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions. Methods: A multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed. Results: CTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance. Conclusion: This study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival.

Comparison of PM2.5 Air Pollution Exposures and Health Effects Associations Using 11 Different Modeling Approaches in the Women's Health Initiative Memory Study (WHIMS).

BACKGROUND: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear. OBJECTIVES: Our objective is to compare particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses. METHODS: We assigned annual PM2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women's Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region. RESULTS: With a few exceptions, relative agreement of approach-specific PM2.5 exposure estimates was high for PM2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM2.5. There was no evidence of large differences in health effects associations with PM2.5 among estimation approaches in analyses adjusted for climate region. CONCLUSIONS: Different estimation approaches produced similar spatial patterns of PM2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM2.5-health effects associations were similar among estimation approaches. PM2.5 estimates and PM2.5-health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest. https://doi.org/10.1289/EHP12995.

The association of long-term exposure to criteria air pollutants, fine particulate matter components, and airborne trace metals with late-life brain amyloid burden in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer's disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants. METHODS: We used a chemical transport model with data fusion to estimate ambient concentrations of PM2.5 and its components, NO2, NOx, O3 (24-hour and 8-hour), CO, and airborne trace metals. We linked concentrations to geocoded participant addresses and calculated 10-year mean exposures (2002 to 2011). Brain amyloid deposition was measured using florbetapir amyloid positron emission tomography (PET) scans in 346 participants without dementia in 2012-2014, and we defined amyloid positivity as a global cortical standardized uptake value ratio ≥ the sample median of 1.2. We used logistic regression models to quantify the association between amyloid positivity and each air pollutant, adjusting for putative confounders. In sensitivity analyses, we considered whether use of alternate air pollution estimation approaches impacted findings for PM2.5, NO2, NOx, and 24-hour O3. RESULTS: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We did not find evidence of associations between long-term exposure to any pollutant and brain amyloid positivity in adjusted models. Findings were materially unchanged in sensitivity analyses using alternate air pollution estimation approaches for PM2.5, NO2, NOx, and 24-hour O3. CONCLUSIONS: Air pollution may impact cognition and dementia independent of amyloid accumulation, though whether air pollution influences AD pathogenesis later in the disease course or at higher exposure levels deserves further consideration.

Electrocatalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid via metal-organic framework-structured hierarchical Co3O4 nanoplate arrays.

Electrocatalytic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) was examined as an alternative to thermocatalytic methods in which two-dimensional (2D) cobalt-metal-organic framework (Co-MOF, ZIF-L-Co) nanoplate arrays were prepared on nickel foam (NF) and then transformed into hierarchical porous Co3O4 nanostructures by chemical etching and low temperature annealing to form electrode materials. Hierarchical porous nanoarrays formed during synthesis enlarged the surface area of the as-prepared catalysts introduced a large number of defects and exposed active sites leading to reduced charge diffusion, improved mass transfer and efficient HMF oxidation. Co3O4/NF electrode materials were able to achieve a current density of 10 mA·cm-2 at an overpotential of 105 mV in 1 M KOH with 10 mM HMF, which was reduced by 175 mV compared with water oxidation. Electrocatalytic oxidation experiments afforded 100 % HMF conversion and 96.7 % FDCA yields with a minimum 96.5 % faradaic efficiency at 1.43 V vs RHE. The proposed MOF-structured synthesis method fundamentally reduces charge diffusion, improves mass transfer of electrodes and is generally applicable to fabrication of hierarchical porous nanostructured materials.

Synthesis of self-renewing Fe(0)-dispersed ordered mesoporous carbon for electrocatalytic reduction of nitrates to nitrogen.

In electrocatalytic reduction of nitrates to nitrogen, key issues are electrode activity, sustainable materials, preparation methods and cost. Herein, lignin, Fe3+ ion, and non-ionic surfactant were combined with evaporation-induced self-assembly (EISA) to prepare zero-valent Fe-dispersed ordered mesoporous carbon (OMC) electrode materials denoted as Fe#OMC. The method developed for preparing Fe-coordinated OMC material avoids the use of toxic phenols, aldehyde reagents and metal doping compounds. When synthesized Fe#OMC samples were applied as electrode materials for the electrocatalytic reduction of nitrate in aqueous solutions, maximum nitrate nitrogen removal was as high as 5373 mg N·g-1 Fe from aqueous solutions containing 400 mg·L-1 NO3--N, while nitrogen selectivity was close to 100%, exceeding catalytic performance of comparable materials. Active hydrogen produced by electrolysis of water during the reaction re-reduced Fe ions formed in the OMC material and stabilized Fe#OMC electrode performance and recycle. The Fe#OMC electrode is self-renewing with respect to its Fe zero-valent state, is simple to prepare from sustainable materials and is effective for electrocatalytic reduction of nitrate or nitrogen-containing compounds in water.

Characteristics of movers and predictors of residential mobility in the Atherosclerosis Risk in Communities (ARIC) cohort.

Current efforts to characterize movers and identify predictors of moving have been limited. We used the ARIC cohort to characterize non-movers, short-distance movers, and long-distance movers, and employed best subset algorithms to identify important predictors of moving, including interactions between characteristics. Short- and long-distance movers were notably different from non-movers, and important predictors of moving differed based on the distance of the residential move. Importantly, systematic inclusion of interaction terms enhanced model fit and was substantively meaningful. This work has important implications for epidemiologic studies of contextual exposures and those treating residential mobility as an exposure.

The Associations of Dietary Copper With Cognitive Outcomes.

Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using 3 cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996-1998 to 2016-2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazard ratio = 1.49, 95% confidence interval: 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta = -0.12, 95% confidence interval: -0.23, -0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment.

Nitrogen biogeochemistry in a boreal headwater stream network in interior Alaska.

High latitude, boreal watersheds are nitrogen (N)-limited ecosystems that export large amounts of organic carbon (C). Key controls on C cycling in these environments are the biogeochemical processes affecting the N cycle. A study was conducted in Nome Creek, an upland tributary of the Yukon River, and two headwater tributaries to Nome Creek, to examine the relation between seasonal and transport-associated changes in C and N pools and N-cycling processes using laboratory bioassays of water and sediment samples and in-stream tracer tests. Dissolved organic nitrogen (DON) exceeded dissolved inorganic nitrogen (DIN) in Nome Creek except late in the summer season, with little variation in organic C:N ratios with time or transport distance. DIN was dominant in the headwater tributaries. Rates of organic N mineralization and denitrification in laboratory incubations were positively correlated with sediment organic C content, while nitrification rates differed greatly between two headwater tributaries with similar drainages. Additions of DIN or urea did not stimulate microbial activity. In-stream tracer tests with nitrate and urea indicated that uptake rates were slow relative to transport rates; simulated rates of uptake in stream storage zones were higher than rates assessed in the laboratory bioassays. In general, N-cycle processes were more active and had a greater overall impact in the headwater tributaries and were minimized in Nome Creek, the larger, higher velocity, transport-dominated stream. Given expectations of permafrost thaw and increased hydrologic cycling that will flush more inorganic N from headwater streams, our results suggest higher N loads from these systems in the future.

Black liquor-derived calcium-activated biochar for recovery of phosphate from aqueous solutions.

Black liquor-derived calcium-activated biochars (Ca-biochar) were synthesized by treating rice straw with Ca(OH)2 to create an adsorbent that was effective for removing phosphate from aqueous waste streams. The Ca(OH)2 acts to separate lignin from the biomass, create pores in the biochar solids and form active adsorption sites. The Ca-biochar adsorbent was efficient for the removal of phosphate from aqueous solutions (pH 1.0 to pH 13.0) with a highest phosphate adsorption capacity of 197 mg/g. Phosphate adsorption was correlated with pseudo-second-order kinetics and the Langmuir model with primary mechanisms being attributed to chemical precipitation and ligand exchange. Application of the Ca-biochar (0.2 g/L) to actual wastewater from a cattle farm (phosphorus content 3.78 mg/L) reduced the phosphorus content to 0.021 mg/L. This work utilizes waste black liquor to prepare functionalized biochar materials, providing a promising approach for black liquor reuse and phosphate removal and recovery from phosphorus-rich waste streams.

Methane and nitrous oxide temporal and spatial variability in two midwestern USA streams containing high nitrate concentrations.

Concentrations and emissions of greenhouse gases CO2, CH4, and N2O commonly are examined individually in aquatic environments in which each is expected to be relatively important; however, their co-occurrence and dynamic interactions in fluvial settings could provide important information about their controlling biogeochemical processes and potential contributions to global climate change. Spatial and temporal variability of CH4, N2O, and CO2 concentrations were measured from June 1999 to September 2003 in two nitrate-rich (40-1200 µM) streams draining agricultural land in the midwestern USA that differed ~13-fold in flow. Seasonal (biweekly), diel (hourly), and transport-oriented (reach-scale) sampling approaches were compared. Dissolved gas concentrations exceeded atmospheric equilibrium values up to 700- and 16-fold, for CH4 and N2O, respectively. Mean concentrations were higher in the larger stream than in the smaller stream. In both streams, CH4 emissions were generally higher in summer-fall and negatively correlated with flow and NO3- concentration while N2O emissions were generally higher in winter/spring and positively correlated with flow and NO3-. In the small stream, diel variations in the concentrations, emissions, and isotopic compositions of CH4, N2O, and NO2- resulted from diel variations in sources, sinks, and air-water gas exchange velocities. Seasonal mean total (CH4 + N2O) area-normalized emission rates, expressed as CO2 warming potential equivalents, were similar for the two streams, but the total reach-scale emission rate for the larger stream, including CO2, was about 2.9 times that of the smaller stream (131.6 vs 46.0 kg CO2 equivalents km-1 day-1, respectively). The CH4 contribution to this flux was 9-28%, despite the relatively high NO3- and O2 concentrations in the streams, indicating contributions from upwelling groundwater or reactions in streambed sediment.

Constraining the Oxygen Isotopic Composition of Nitrate Produced by Nitrification.

Measurements of the stable isotope ratios of nitrogen (15N/14N) and oxygen (18O/16O) in nitrate (NO3-) enable identification of sources, dispersal, and fate of natural and contaminant NO3- in aquatic environments. The 18O/16O of NO3- produced by nitrification is often assumed to reflect the proportional contribution of oxygen atom sources, water, and molecular oxygen, in a 2:1 ratio. Culture and seawater incubations, however, indicate oxygen isotopic equilibration between nitrite (NO2-) and water, and kinetic isotope effects for oxygen atom incorporation, which modulate the NO3- 18O/16O produced during nitrification. To investigate the influence of kinetic and equilibrium effects on the isotopic composition of NO3- produced from the nitrification of ammonia (NH3), we incubated streamwater supplemented with ammonium (NH4+) and increments of 18O-enriched water. Resulting NO3- 18O/16O ratios showed (1) a disproportionate sensitivity to the 18O/16O ratio of water, mediated by isotopic equilibration between water and NO2-, as well as (2) kinetic isotope discrimination during O atom incorporation from molecular oxygen and water. Empirically, the NO3- 18O/16O ratios thus produced fortuitously converge near the 18O/16O ratio of water. More elevated NO3- 18O/16O values commonly reported in soils and oxic groundwater may thus derive from processes additional to nitrification, including NO3- reduction.

School start times and teenage driver motor vehicle crashes.

INTRODUCTION: Shifting school start times to 8:30 am or later has been found to improve academic performance and reduce behavior problems. Limited research suggests this may also reduce adolescent driver motor vehicle crashes. A change in the school start time from 7:30 am to 8:45 am for all public high schools in one North Carolina county presented the opportunity to address this question with greater methodologic rigor. METHOD: We conducted ARIMA interrupted time-series analyses to examine motor vehicle crash rates of high school age drivers in the intervention county and 3 similar comparison counties with comparable urban-rural population distribution. To focus on crashes most likely to be affected, we limited analysis to crashes involving 16- & 17-year-old drivers occurring on days when school was in session. RESULTS: In the intervention county, there was a 14% downward shift in the time-series following the 75 min delay in school start times (p = .076). There was no change approaching statistical significance in any of the other three counties. Further analysis indicated marked, statistically significant shifts in hourly crash rates in the intervention county, reflecting effects of the change in school start time on young driver exposure. Crashes from 7 to 7:59 am decreased sharply (-25%, p = .008), but increased similarly from 8 to 8:59 am (21%, p = .004). Crashes from 2 to 2:59 pm declined dramatically (-48%, p = .000), then increased to a lesser degree from 3 to 3:59 pm (32%, p = .024) and non-significantly from 4 to 4:59 (19%, p = .102). There was no meaningful change in early morning or nighttime crashes, when drowsiness-induced crashes might have been expected to be most common. DISCUSSION: The small decrease in crashes among high school age drivers following the shift in school start time is consistent with the findings of other studies of teen driver crashes and school start times. All these studies, including the present one, have limitations, but the similar findings suggest that crashes and school start times are indeed related, with earlier start times equating to more crashes. CONCLUSION: Later high school start times (>8:30 am) appear to be associated with lower adolescent driver crash rates, but additional research is needed to confirm this and to identify the mechanism by which this occurs (reduced drowsiness or reduced exposure).

The reliability of identifying the Omega sign using axial T2-weighted magnetic resonance imaging.

Preoperative identification of the eloquent brain is important for neurosurgical planning. One common method of finding the motor cortex is by localizing "the Omega sign." No studies have tested the reliability of imaging to identify the Omega sign. We identified 40 recent and consecutive patients who had undergone preoperative functional magnetic resonance imaging for identification of the hand motor area prior to tumor resection. We recruited 11 neurosurgical residents of various levels of training and one board-certified neurosurgeon to identify the hand motor cortex Omega. Testees were given axial images of T2-weighted MRI and placed marks where they expected to find the Omega. Two board-certified radiologists graded and quantified the localization attempts. Inter-rater reliability was assessed using the kappa statistic, and Rao-Scott chi-square tests were used to examine the relationship between clinical factors and testees' experience with correct identification of the Omega sign. The overall correct identification rate was 69.9% (95% CI = 63.4-75.7), ranging from 36.6% to 92.7% among all raters for the tumor side and from 46.2% to 97.4% for the non-tumor side. Anatomic distortion greatly affected correct identification ( p < 0.005). Senior residents had a significantly higher rate of identification of the Omega than junior residents ( p < 0.001). Overall, inter-rater reliability for the Omega sign is poor, with a Fleiss kappa of 0.23. We concluded that correct identification of the Omega sign is affected by tumor distortion and experience but overall is not reliable. This underscores the limitations of anatomic landmarks and the importance of utilizing multiple scanning planes and preoperative fMRI for appropriate localization.

Air quality and acute deaths in California, 2000-2012.

Many studies have shown an association between air quality and acute deaths, and such associations are widely interpreted as causal. Several factors call causation and even association into question, for example multiple testing and multiple modeling, publication bias and confirmation bias. Many published studies are difficult or impossible to reproduce because of lack of access to confidential data sources. Here we make publically available a dataset containing daily air quality levels, PM2.5 and ozone, daily temperature levels, minimum and maximum and daily maximum relative humidity levels for the eight most populous California air basins, thirteen years, >2M deaths, over 37,000 exposure days. The data are analyzed using standard time series analysis, and a sensitivity analysis is computed varying model parameters, locations and years. Our analysis finds little evidence for association between air quality and acute deaths. These results are consistent with those for the widely cited NMMAPS dataset when the latter are restricted to California. The daily death variability was mostly explained by time of year or weather variables; Neither PM2.5 nor ozone added appreciably to the prediction of daily deaths. These results call into question the widespread belief that association between air quality and acute deaths is causal/near-universal.