Substantial increases in wildfire activity have been recorded in recent decades. Wildfires influence the chemical composition and concentration of particulate matter ≤2.5 μm in aerodynamic diameter ...(PM2.5). However, relatively few epidemiologic studies focus on the health impacts of wildfire smoke PM2.5 compared with the number of studies focusing on total PM2.5 exposure.
We estimated the associations between cardiorespiratory acute events and exposure to smoke PM2.5 in Colorado using a novel exposure model to separate smoke PM2.5 from background ambient PM2.5 levels.
We obtained emergency department visits and hospitalizations for acute cardiorespiratory outcomes from Colorado for May–August 2011–2014, geocoded to a 4 km geographic grid. Combining ground measurements, chemical transport models, and remote sensing data, we estimated smoke PM2.5 and non-smoke PM2.5 on a 1 km spatial grid and aggregated to match the resolution of the health data. Time-stratified, case-crossover models were fit using conditional logistic regression to estimate associations between fire smoke PM2.5 and non-smoke PM2.5 for overall and age-stratified outcomes using 2-day averaging windows for cardiovascular disease and 3-day windows for respiratory disease.
Per 1 μg/m3 increase in fire smoke PM2.5, statistically significant associations were observed for asthma (OR = 1.081 (1.058, 1.105)) and combined respiratory disease (OR = 1.021 (1.012, 1.031)). No significant relationships were evident for cardiovascular diseases and smoke PM2.5. Associations with non-smoke PM2.5 were null for all outcomes. Positive age-specific associations related to smoke PM2.5 were observed for asthma and combined respiratory disease in children, and for asthma, bronchitis, COPD, and combined respiratory disease in adults. No significant associations were found in older adults.
This is the first multi-year, high-resolution epidemiologic study to incorporate statistical and chemical transport modeling methods to estimate PM2.5 exposure due to wildfires. Our results allow for a more precise assessment of the population health impact of wildfire-related PM2.5 exposure in a changing climate.
•Wildfire PM2.5 associated with asthma and combined respiratory diseases•Children displayed significant associations between smoke exposure and asthma.•Wildfire PM2.5 associated with asthma, bronchitis, combined respiratory in adults•Older adults did not exhibit associations with examined respiratory outcomes.•Cardiovascular outcomes not associated in grouped or stratified analysis
In this paper, the lateral migration of a neutrally buoyant spherical particle in the pressure-driven rectangular channel flow of an Oldroyd-B fluid is numerically investigated with a fictitious ...domain method. The aspect ratio of the channel cross-section considered is 1 and 2, respectively. The particle lateral motion trajectories are shown for the bulk Reynolds number ranging from 1 to 100, the ratio of the solvent viscosity to the total viscosity being 0.5, and a Weissenberg number up to 1.5. Our results indicate that the lateral equilibrium positions located on the cross-section midline, diagonal line, corner and channel centreline occur successively as the fluid elasticity is increased, for particle migration in square channel flow with finite fluid inertia. The transition of the equilibrium position depends strongly on the elasticity number (the ratio of the Weissenberg number to the Reynolds number) and weakly on the Reynolds number. The diagonal-line equilibrium position occurs at an elasticity number ranging from roughly 0.001 to 0.02, and can coexist with the midline and corner equilibrium positions. When the fluid inertia is negligibly small, particles migrate towards the channel centreline, or the closest corner, depending on their initial positions and the Weissenberg number, and the corner attractive area first increases and then decreases as the Weissenberg number increases. For particle migration in a rectangular channel with an aspect ratio of 2, the transition of the equilibrium position from the midline, ‘diagonal line’ (the line where two lateral shear rates are equal to each other), off-centre long midline and channel centreline takes place as the Weissenberg number increases at moderate Reynolds numbers. An off-centre equilibrium position on the long midline is observed for a large blockage ratio of 0.3 (i.e. the ratio of the particle diameter to the channel height is 0.3) at a low Reynolds number. This off-centre migration is driven by shear forces, unlike the elasticity-induced rapid inward migration, which is driven by the normal force (pressure or first normal stress difference).
Summary Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in ...vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study–Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov ( NCT01689246 ) and the European Union Clinical Trials Registry (2012-002866-11). Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control n=354, 6·32, 95% CI 5·31−7·34: 75 mg LMTM twice a day n=257 −0·02, −1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day n=250 −0·43, −2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control −8·22, 95% CI −9·63 to −6·82: 75 mg LMTM twice a day −0·93, −3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day −0·34, −2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. Funding TauRx Therapeutics.
Abstract The National Institute on Aging and the Alzheimer’s Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer’s disease (AD), ...referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.
Objectives: To review a series of noninvasive encapsulated follicular variant of papillary thyroid carcinomas (FVPTCs) in an attempt to further define the role of cytopathology in the diagnosis of ...noninvasive follicular thyroid neoplasm with papillary-like nuclear features and invasive FVPTC.
Methods: Surgical pathology cases diagnosed as FVPTC with correlating thyroid fine-needle aspiration (FNA) were identified and divided into two FVPTC groups: noninvasive and invasive. Cytologic diagnoses were compared between them.
Results: We identified 23 cases that met the criteria for noninvasive FVPTC and 27 cases that were typical infiltrative FVPTC (n = 16) or encapsulated FVPTC with either capsular and/or lymphovascular invasion (n = 11). Of the noninvasive FVPTC cases, there were four benign lesions, 14 follicular lesions of undetermined significance (FLUS), four follicular neoplasms (FNs), one suspicious case, and no papillary thyroid carcinomas (PTCs). In the invasive FVPTC group, there were no benign cases, four FLUS, three FNs, 12 suspicious cases, and eight PTCs.
Conclusions: There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC (P < .05).
The ability of certain components of particulate matter to induce oxidative stress through the generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed ...linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and report here the development of a similar semi-automated system for the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed for a host of aerosol species, along with AA and DTT activities. We present a detailed contrast in findings from these two assays. Water-soluble AA activity was higher in summer and fall than in winter, with highest levels near heavily trafficked highways, whereas DTT activity was higher in winter compared to summer and fall and more spatially homogeneous. AA activity was nearly exclusively correlated with water-soluble Cu (r- = -0.70-0.94 at most sites), whereas DTT activity was correlated with organic and metal species. Source apportionment models, positive matrix factorization (PMF) and a chemical mass balance method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from traffic emissions and secondary processes (e.g., organic aerosol oxidation or metals mobilization by secondary acids) to both AA and DTT activities in urban Atlanta. In contrast, biomass burning was a large source for DTT activity, but insignificant for AA. AA activity was not correlated with PM2.5 mass, while DTT activity co-varied strongly with mass (r- = -0.49-0.86 across sites and seasons). Various linear models were developed to estimate AA and DTT activities for the central Atlanta Jefferson Street site, based on the CMB-E sources. The models were then used to estimate daily oxidative potential at this site over the 1998-2009 period. Time series epidemiological analyses were conducted to assess daily emergency department (ED) visits data for the five-county Atlanta metropolitan area based on the estimated 10-year backcast oxidative potential. Estimated AA activity was not statistically associated with any tested health outcome, while DTT activity was associated with ED visits for both asthma or wheeze and congestive heart failure. The findings point to the importance of both organic components and transition metals from biomass burning and mobile sources to adverse health outcomes in this region.
While the growth of mobile applications brings enjoyment to daily life, it also imposes more complicated traffic situations on wireless networks. A complete understanding of the impact from the ...traffic profile is thus essential for network operators to deploy next generation small cell networks. In this paper, based on stochastic geometry and queuing theory, we develop a mathematical framework that captures the interplay between the spatial location of small access points, which determines the magnitude of mutual interference, and their temporal traffic dynamic. We derive a tractable expression for the SINR distribution, and verify its accuracy via simulations. Based on our analysis, we find that: 1) under the same configuration, when traffic condition changes from light to heavy, the corresponding SINR requirement can differ by more than 10 dB for the network to maintain coverage; 2) the SINR coverage probability varies largely with traffic fluctuation in the sub-medium load regime, whereas in a scenario with a very light traffic load, the SINR outage probability increases linearly with the packet arrival rate; and 3) spatial densification can boost the cell-edge rate almost linearly in the dense regime, and thus confirms the appeal for ultra-dense deployment of small cells in the next generation wireless network.
The accuracy in estimated fine particulate matter concentrations (PM2.5), obtained by fusing of station-based measurements and satellite-based aerosol optical depth (AOD), is often reduced without ...accounting for the spatial and temporal variations in PM2.5 and missing AOD observations. In this study, a city-specific linear regression model was first developed to fill in missing AOD data. A novel interpolation-based variable, PM2.5 spatial interpolator (PMSI2.5), was also introduced to account for the spatial dependence in PM2.5 across grid cells. A Bayesian hierarchical model was then developed to estimate spatiotemporal relationships between AOD and PM2.5. These methods were evaluated through a city-specific 10-fold cross-validation procedure in a case study in North China in 2014. The cross validation R 2 was 0.61 when PMSI2.5 was included and 0.48 when PMSI2.5 was excluded. The gap-filled AOD values also effectively improved predicted PM2.5 concentrations with an R 2 = 0.78. Daily ground-level PM2.5 concentration fields at a 12 km resolution were predicted with complete spatial and temporal coverage. This study also indicates that model prediction performance should be assessed by accounting for monitor clustering due to the potential misinterpretation of model accuracy in spatial prediction when validation monitors are randomly selected.
PDF
