Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States.

Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. fumigatus infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant A. fumigatus has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in A. fumigatus are tandem repeats (TR) in the cyp51A promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant A. fumigatus has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant A. fumigatus in the U.S., we collected isolates from agricultural sites in eight states and tested 202 isolates for sensitivity to azoles. We found azole-resistant A. fumigatus in agricultural environments in seven states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades, and TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow indicating recombination between clades highlighting the potential for azole-resistance to continue spreading in the U.S.IMPORTANCEAspergillus fumigatus is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris, and compost. Azoles are the first line of defense antifungal drugs against A. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant A. fumigatus has been a problem in Europe and Asia for 20 years and has recently been reported in patients in the United States (U.S.). Until this study, we did not know much about azole-resistant A. fumigatus in agricultural settings in the U.S. In this study, we isolated azole-resistant A. fumigatus from multiple states and compared it to isolates from around the world. We show that A. fumigatus which is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.

Active school transport and fast food intake: Are there racial and ethnic differences?

OBJECTIVES: To investigate whether active school transport was associated with fast food consumption, and to examine differences across racial/ethnic groups. METHODS: Adolescent data (n=3194) from the 2009 California Health Interview Survey were analyzed with logistic regression models to examine the association between active school transport (AST) and fast food intake across racial/ethnic groups. RESULTS: In the overall sample, AST during 1-2days in the past week was associated with greater likelihood of fast food intake (OR: 1.58; 95% CI: 1.03-2.43), compared with zero days of AST, controlling for demographic and other factors. The association between AST and fast food intake differed significantly by race/ethnicity (p<0.01). Among Latino adolescents, greater frequency of AST was significantly associated with greater likelihood of fast food intake (1-2days OR, 2.37, 95%CI: 1.05-5.35; 3-4days OR, 2.78, 95% CI: 1.04-7.43; 5days OR, 2.20, 95%CI: 1.23-3.93). Among White and Asian adolescents, there was a curvilinear pattern: relative to adolescents who reported zero days of AST, those who did AST 1-2days/week had greater likelihood of fast food intake, but AST of 3-4days and 5days/week was associated respectively, with higher and lower likelihood of fast food intake among both groups. CONCLUSIONS: AST appears to be a risk factor for fast food intake, and may expose some ethnic groups more than others to increased opportunity to purchase and consume fast food. Programs and policies to promote AST among adolescents should incorporate efforts to encourage healthy eating and discourage concentration of fast food outlets near schools.

A method for measuring the interfacial tension for density-matched liquids.

We propose a method to measure the interfacial tension characterizing the interface between two immiscible liquids of practically the same density. In this method, a cylindrical liquid bridge made of one the liquids is vibrated laterally inside a tank filled with the other. The first resonance frequency is determined and equated to the first eigenfrequency of the m=1 linear mode to infer the interfacial tension value. The method does not involve the density jump across the interface. Therefore, its accuracy is affected neither by the smallness of the Bond number nor by errors of the density difference. The experimental setup is relatively simple, and the procedure does not use image processing techniques. The results satisfactorily agree with those measured by TIFA-AI (Theoretical Fitting Image Analysis-Axisymmetric Interfaces) for the same liquid bridges when the density difference is sufficiently large for TIFA-AI to be valid. We conduct numerical simulations of the Navier-Stokes equations to determine the best parameter conditions for the proposed method. The transfer function characterizing the frequency response of the fluid configuration is measured in some experiments to quantify non-linear effects and to study the role played by the outer bath vibration.

Predicting ischaemic stroke subtype from presenting systolic blood pressure: the BASIC Project.

OBJECTIVE: We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. DESIGN: Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population-based study. Multinomial logistic regression was used to examine the association between stroke subtype and first documented SBP in the medical record. SETTING: Nueces County, TX, USA (313,645 residents in 2000). The community is urban with the majority of the population residing in the city of Corpus Christi. The area is served by seven adult acute care hospitals. PATIENTS: Three hundred and eight cases with completed ischaemic stroke and determined subtype aetiology between January 2000 and December 2002. RESULTS: Lower presenting SBP was associated with stroke subtype (P = 0.001). This association remained significant in the final model adjusted for age and history of coronary artery disease. The odds of cardioembolic versus small vessel occlusion increased by 20% (OR = 1.20, 95% CI: 1.07-1.35) for every 10 mmHg decrease in presenting SBP. Other covariates including race/ethnicity, gender, history of hypertension, and diabetes were neither significant predictors of stroke subtype, nor did they confound the association of SBP and stroke subtype. A 5 year increase in age increased the odds of cardioembolic subtype by 25% (OR = 1.25, 95% CI: 1.07-1.47). CONCLUSIONS: Lower initial SBP and older age at ischaemic stroke presentation were associated with cardioembolic stroke. Suspicion of cardioembolic stroke should be increased in those presenting with low SBP.

Residual-based diagnostics for structural equation models.

Classical diagnostics for structural equation models are based on aggregate forms of the data and are ill suited for checking distributional or linearity assumptions. We extend recently developed goodness-of-fit tests for correlated data based on subject-specific residuals to structural equation models with latent variables. The proposed tests lend themselves to graphical displays and are designed to detect misspecified distributional or linearity assumptions. To complement graphical displays, test statistics are defined; the null distributions of the test statistics are approximated using computationally efficient simulation techniques. The properties of the proposed tests are examined via simulation studies. We illustrate the methods using data from a study of in utero lead exposure.

Exposure to Bisphenol A and phthalates metabolites in the third trimester of pregnancy and BMI trajectories.

BACKGROUND: Bisphenol A (BPA) and phthalates metabolites are linked to a variety of adverse health consequences but studies have not explored their association with growth trajectories. OBJECTIVE: Explore body mass index (BMI) trajectories for tertile exposures to BPA and phthalates metabolites in the third trimester of pregnancy. METHODS: We constructed BMI (kg/m2 ) trajectories from birth to 14 years in a birth cohort of 249 children from Mexico City using tertiles of third trimester maternal urinary concentrations of BPA and phthalates metabolites. Fractional age polynomials and mixed effects models were fit separately by sex. Predicted models were plotted for each metabolite tertile with the covariates mother's education and BMI centered at average values. RESULTS: Highest predicted BMI trajectories for female children were observed for third tertile exposure to the phthalate metabolite mono(2-ethyl-5-carboxypentyl) phthalate. In male children, first tertile exposure to mono-isobutyl phthalate and monobenzyl phthalate and second tertile exposure to mono(2-ethylhexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate predicted the highest BMI trajectory by adolescence. There was no relationshsip between BPA and child growth trajectory. CONCLUSIONS: These results suggest sex-specific differences in BMI trajectories by levels of metabolite exposure. Additional studies are needed to consider growth through adolescence in assessing the association of pregnancy exposures on child's BMI.

Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City.

Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36-47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28-0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.

Generation of micro-sized PDMS particles by a flow focusing technique for biomicrofluidics applications.

Polydimethylsiloxane (PDMS), due to its remarkable properties, is one of the most widely used polymers in many industrial and medical applications. In this work, a technique based on a flow focusing technique is used to produce PDMS spherical particles with sizes of a few microns. PDMS precursor is injected through a hypodermic needle to form a film/reservoir over the needle's outer surface. This film flows towards the needle tip until a liquid ligament is steadily ejected thanks to the action of a coflowing viscous liquid stream. The outcome is a capillary jet which breaks up into PDMS precursor droplets due to the growth of capillary waves producing a micrometer emulsion. The PDMS liquid droplets in the solution are thermally cured into solid microparticles. The size distribution of the particles is analyzed before and after curing, showing an acceptable degree of monodispersity. The PDMS liquid droplets suffer shrinkage while curing. These microparticles can be used in very varied technological fields, such as biomedicine, biotechnology, pharmacy, and industrial engineering.

Enrollment of women and minorities in NINDS trials.

OBJECTIVE: To determine policy-associated changes over time in 1) the enrollment of women and minorities in National Institute of Neurological Disorders and Stroke (NINDS)-funded clinical trials and 2) the trial publication reporting of race/ethnicity and gender. METHODS: All NINDS-funded phase III trials published between 1985 and 2008 were identified. Percent of African Americans, Hispanic Americans, and women enrolled in the trials was calculated for those trials with available data. Z tests were used to compare reporting and enrollment data from before (period 1) and after (period 2) 1995 when NIH enacted their policies regarding race, ethnicity, and gender. Percent of main trial publications reporting enrollment of African Americans, Hispanic Americans, and women was also calculated. RESULTS: Of the 56 trials identified, 100%, 48%, and 25% reported enrollment by gender, race, and ethnicity. Women constituted 42.1% of the trial population. Enrollment of women increased over time (36.9% period 1; 49.0% period 2, p < 0.001). African Americans constituted 19.8% of the enrollees in trials with available data and enrollment increased over time (11.6% period 1; 30.7% period 2, p < 0.001). Hispanic Americans constituted 5.8% of subjects in trials with available data and enrollment decreased over time (7.4% period 1; 5.0% period 2, p < 0.001). CONCLUSIONS: Improvements in reporting of race/ethnicity in publications and enrollment of Hispanics in NINDS trials are needed. While African American representation is above population levels, Hispanic Americans are underrepresented in NINDS trials and representation is declining despite Hispanics' increasing representation in the US population.

Associations of salivary cortisol levels with metabolic syndrome and its components: the multi-ethnic study of atherosclerosis.

CONTEXT: Prior research has identified associations between social-environmental factors and metabolic syndrome (MetS) components. The physiological mechanisms underlying these associations are not fully understood, but alterations in activity of the hypothalamic-pituitary-adrenal axis, a stress-responsive biological system, have been hypothesized to play a role. OBJECTIVE: The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, high-density lipoproteins, glucose, and blood pressure) are associated with cortisol levels. DESIGN AND SETTING: We conducted cross-sectional analyses of data from the Multi-Ethnic Study of Atherosclerosis (MESA) study in the general community. PATIENTS OR OTHER PARTICIPANTS: We studied a population-based sample of 726 adults (ages 48 to 89 yr) who do not have clinical diabetes. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): Cortisol awakening response, cortisol decline across the waking day, and total cortisol output were analyzed (using 18 timed measures of salivary cortisol over 3 d). RESULTS: Overall, we found little evidence that the presence of MetS or its components is related to cortisol output or patterns. Contrary to expectation, the presence of MetS was associated with lower rather than higher area under the curve, and no consistent pattern was observed when MetS components or subsets of components were examined in relation to cortisol. CONCLUSIONS: Our findings do not support the hypothesis that differences in level or diurnal pattern of salivary cortisol output are associated with MetS among persons without clinical diabetes.

Do-not-resuscitate orders and predictive models after intracerebral hemorrhage.

OBJECTIVE: To quantify the accuracy of commonly used intracerebral hemorrhage (ICH) predictive models in ICH patients with and without early do-not-resuscitate orders (DNR). METHODS: Spontaneous ICH cases (n = 487) from the Brain Attack Surveillance in Corpus Christi study (2000-2003) and the University of California, San Francisco (June 2001-May 2004) were included. Three models (the ICH Score, the Cincinnati model, and the ICH grading scale [ICH-GS]) were compared to observed 30-day mortality with a chi(2) goodness-of-fit test first overall and then stratified by early DNR orders. RESULTS: Median age was 71 years, 49% were female, median Glasgow Coma Scale score was 12, median ICH volume was 13 cm(3), and 35% had early DNR orders. Overall observed 30-day mortality was 42.7% (95% confidence interval [CI] 38.3-47.1), with the average model-predicted 30-day mortality for the ICH Score, Cincinnati model, and ICH-GS at 39.9% (p = 0.005), 40.4% (p = 0.007), and 53.9% (p < 0.001). However, for patients with early DNR orders, the observed 30-day mortality was 83.5% (95% CI 78.0-89.1), with the models predicting mortality of 64.8% (p < 0.001), 57.2% (p < 0.001), and 77.8% (p = 0.02). For patients without early DNR orders, the observed 30-day mortality was 20.8% (95% CI 16.5-25.7), with the models predicting mortality of 26.6% (p = 0.05), 31.4% (p < 0.001), and 41.1% (p < 0.001). CONCLUSIONS: ICH prognostic model performance is substantially impacted when stratifying by early DNR status, possibly giving a false sense of model accuracy when DNR status is not considered. Clinicians should be cautious when applying these predictive models to individual patients.

Combining data from primary and ancillary surveys to assess the association between neighborhood-level characteristics and health outcomes: the Multi-Ethnic Study of Artherosclerosis.

There is increasing interest in understanding the role of neighborhood-level factors on the health of individuals. Many large-scale epidemiological studies that accurately measure health status of individuals and individual risk factors exist. Sometimes these studies are linked to area-level databases (e.g. census) to assess the association between crude area-level characteristics and health. However, information from such databases may not measure the neighborhood-level constructs of interest. More recently, large-scale epidemiological studies have begun collecting data to measure specific features of neighborhoods using ancillary surveys. The ancillary surveys are composed of a separate, typically larger, set of individuals. The challenge is then to combine information from these two surveys to assess the role of neighborhood-level factors. We propose a method for combining information from the two data sources using a likelihood-based framework. We compare it with currently used ad hoc approaches via a simulation study. The simulation study shows that the proposed approach yields estimates with better sampling properties (less bias and better coverage probabilities) compared with the other approaches. However, there are cases where some ad hoc approaches may provide adequate estimates. We also compare the methods by applying them to the Multi-Ethnic Study of Atherosclerosis and its Neighborhood Ancillary Survey.

Gender and ethnic differences in subarachnoid hemorrhage.

BACKGROUND: Mexican Americans (MAs) comprise the largest component of the largest minority group within the United States. The purpose of this study was to examine ethnic and gender differences in the epidemiology, presentation, and outcomes after subarachnoid hemorrhage (SAH) in a representative United States community. Targeted public health interventions are dependent on accurate assessments of groups at highest disease risk. METHODS: All patients with nontraumatic SAH older than 44 years were prospectively identified from January 1, 2000, to December 31, 2006, as part of the Brain Attack Surveillance In Corpus Christi project, an urban population-based study in southeast Texas. Risk ratios for cumulative SAH incidence comparing MAs with non Hispanic whites (NHWs) and women with men were calculated. Descriptive statistics for other clinical and demographic variables were computed overall, by gender, and by ethnicity. RESULTS: A total of 107 patients had a SAH during the time period (7-year cumulative incidence: 11/10,000); of these, 43 were NHW (40% of cases vs 53% of the population) and 64 were MA (60% of cases vs 48% of the population). The overall age-adjusted risk ratio for SAH in MAs compared with NHWs was 1.67 (95% CI: 1.13, 2.47), and in women compared to men was 1.74 (95% CI 1.16, 2.62). Overall in-hospital mortality was 32.2%. No ethnic difference was observed for discharge disability or in-hospital mortality. CONCLUSIONS: Subarachnoid hemorrhage disproportionately affects Mexican Americans and women. Public health interventions should target these groups to reduce the impact of this severe disease.