Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Predictors of betel quid chewing behavior and cessation patterns in Taiwan aborigines

BACKGROUND: Betel quid, chewed by about 600 million people worldwide, is one of the most widely used addictive substances. Cessation factors in betel quid chewers are unknown. The present study explores prevalence and the quit rate of betel quid chewing in Taiwan aborigines. Our goal was to delineate potential predictors of chewing cessation. METHODS: A stratified random community-based survey was designed for the entire aborigines communities in Taiwan. A total of 7144 participants were included between June 2003 and May 2004 in this study. Information on sociodemographic characteristics, such as gender, age, obesity, education years, marital status, ethnicity, and habits of betel quid chewing, smoking and drinking was collected by trained interviewers. RESULTS: The prevalence of betel quid chewers was 46.1%. Betel quid chewing was closely associated with obesity (OR = 1.61; 95% CI: 1.40–1.85). Betel quid chewers were most likely to use alcohol and cigarettes together. Quit rate of betel quid chewers was 7.6%. Betel quid chewers who did not drink alcohol were more likely to quit (OR = 1.89; 95% CI: 1.43–2.50). Alcohol use is a significant factor related to cessation of betel quid chewing, but smoking is not. CONCLUSION: Taiwan aborigines have a high prevalence of betel quid chewers and a low quit rate. Alcohol use is strongly association with betel quid chewing. Efforts to reduce habitual alcohol consumption might be of benefit in cessation of betel quid chewing

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil

BACKGROUND: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil. METHODS: Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression. RESULTS: Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model. CONCLUSION: Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption

Geocoding rural addresses in a community contaminated by PFOA: a comparison of methods

BACKGROUND: Location is often an important component of exposure assessment, and positional errors in geocoding may result in exposure misclassification. In rural areas, successful geocoding to a street address is limited by rural route boxes. Communities have assigned physical street addresses to rural route boxes as part of E911 readdressing projects for improved emergency response. Our study compared automated and E911 methods for recovering and geocoding valid street addresses and assessed the impact of positional errors on exposure classification. METHODS: The current study is a secondary analysis of existing data that included 135 addresses self-reported by participants of a rural community study who were exposed via public drinking water to perfluorooctanoate (PFOA) released from a DuPont facility in Parkersburg, West Virginia. We converted pre-E911 to post-E911 addresses using two methods: automated ZP4 address-correction software with the U.S. Postal Service LACS database and E911 data provided by Wood County, West Virginia. Addresses were geocoded using TeleAtlas, an online commercial service, and ArcView with StreetMap Premium North America NAVTEQ 2008 enhanced street dataset. We calculated positional errors using GPS measurements collected at each address and assessed exposure based on geocoded location in relation to public water pipes. RESULTS: The county E911 data converted 89% of the eligible addresses compared to 35% by ZP4 LACS. ArcView/NAVTEQ geocoded more addresses (n = 130) and with smaller median distance between geocodes and GPS coordinates (39 meters) than TeleAtlas (n = 85, 188 meters). Without E911 address conversion, 25% of the geocodes would have been more than 1000 meters from the true location. Positional errors in TeleAtlas geocoding resulted in exposure misclassification of seven addresses whereas ArcView/NAVTEQ methods did not misclassify any addresses. CONCLUSIONS: Although the study was limited by small numbers, our results suggest that the use of county E911 data in rural areas increases the rate of successful geocoding. Furthermore, positional accuracy of rural addresses in the study area appears to vary by geocoding method. In a large epidemiological study investigating the health effects of PFOA-contaminated public drinking water, this could potentially result in exposure misclassification if addresses are incorrectly geocoded to a street segment not serviced by public water

Optical Control of Mammalian Endogenous Transcription and Epigenetic States

The dynamic nature of gene expression enables cellular programming, homeostasis, and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high precision spatiotemporal control of many cellular functions1-11. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here, we describe the development of Light-Inducible Transcriptional Effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain12-14 with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical co-factors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility3,4,6,7,15. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of awake mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin

Frequency-stabilization to 6x10^-16 via spectral-hole burning

We demonstrate two-stage laser stabilization based on a combination of Fabry- Perot and spectral-hole burning techniques. The laser is first pre-stabilized by the Fabry-Perot cavity to a fractional-frequency stability of sigma_y(tau) < 10^-13. A pattern of spectral holes written in the absorption spectrum of Eu3+:Y2SiO5 serves to further stabilize the laser to sigma_y(tau) = 6x10^-16 for 2 s < tau < 8 s. Measurements characterizing the frequency sensitivity of Eu3+:Y2SiO5 spectral holes to environmental perturbations suggest that they can be more frequency stable than Fabry-Perot cavities

Multidisciplinary team meetings and their impact on workflow in radiology and pathology departments

<p>Abstract</p> <p>Background</p> <p>The development of multidisciplinary team meetings (MDTMs) for radiology and pathology is a burgeoning area that increasingly impacts on work processes in both of these departments. The aim of this study was to examine work processes and quantify the time demands on radiologists and pathologists associated with MDTM practices at a large teaching hospital. The observations reported in this paper reflect a general trend affecting hospitals and our conclusions will have relevance for others implementing clinical practice guidelines.</p> <p>Methods</p> <p>For one month, all work related to clinical meetings between pathology and radiology with clinical staff was documented and later analysed.</p> <p>Results</p> <p>The number of meetings to which pathology and radiology contribute at a large university teaching hospital, ranges from two to eight per day, excluding grand rounds, and amounts to approximately 50 meetings per month for each department. For one month, over 300 h were spent by pathologists and radiologists on 81 meetings, where almost 1000 patients were discussed. For each meeting hour, there were, on average, 2.4 pathology hours and 2 radiology hours spent in preparation. Two to three meetings per week are conducted over a teleconferencing link. Average meeting time is 1 h. Preparation time per meeting ranges from 0.3 to 6 h for pathology, and 0.5 to 4 for radiology. The review process in preparation for meetings improves internal quality standards. Materials produced externally (for example imaging) can amount to almost 50% of the material to be reviewed on a single patient. The number of meetings per month has increased by 50% over the past two years. Further increase is expected in both the numbers and duration of meetings when scheduling issues are resolved. A changing trend in the management of referred patients with the development of MDTMs and the introduction of teleconferencing was noted.</p> <p>Conclusion</p> <p>Difficulties are being experienced by pathology and radiology departments participating fully in several multidisciplinary teams. Time spent at meetings, and in preparation for MDTMs is significant. Issues of timing and the coordination of materials to be reviewed are sometimes irreconcilable. The exchange of patient materials with outside institutions is a cause for concern when full data are not made available in a timely fashion. The process of preparation for meetings is having a positive influence on quality, but more resources are needed in pathology and radiology to realise the full benefits of multidisciplinary team working.</p