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Abstract Background The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations. Methods Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case–control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses. Results Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV1/FVC ( $$\beta$$ β 0.020, SE 0.004, p 4.97 × 10–08), with suggestive evidence of association with FEV1 ( $$\beta$$ β 0.092, SE 0.018, p 3.40 × 10–07). Sex-stratified analyses revealed X chromosome variants that were differentially trending in one sex, with significantly different effect sizes or directions. Conclusions This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.

The ability to image strain fields in composite materials is an indispensable necessity for structural health monitoring. Embedded electromagnetic metamaterials sensitive to applied stresses and operating in the terahertz regime have been proposed as a solution, but they have traditionally relied on slight amplitude or frequency shifts of their terahertz spectral resonance relative to a presumably unchanging, unstrained reference spectral map. Here, we demonstrate a facile, reference-free imaging technique to map the currently active local strain throughout a composite structure using a reversible passive terahertz metamaterial laminate with a tailored polarimetric signature. Only two orthogonal polarizations and a few frequencies are required to measure this strong terahertz response, from which the local strain environment may be rapidly and quantitatively mapped over large areas.

In this letter, we discuss how to prepare millions of uniform p-type silicon (Si) microparticles using top-down fabrication processes and how to remotely control their dynamics when they are suspended in water and powered by external alternating current (AC) electric fields. These microparticles present positively charged carrier types (majority carriers from boron atom doping in the intrinsic Si) and negatively charged carrier types (minority carriers from the free electrons in the Si lattice), which electrostatically affects their negatively charged surfaces and enables a variety of programmable behaviors, such as directional assembly and propulsion. At high AC electric field frequencies ( f > 10 kHz), the microparticles assemble by attractive dielectrophoretic polarization forces. At low electric field frequencies ( f ≤ 10 kHz), the microparticles propel by induced-charge electrophoretic flows. The ability to manipulate the electrostatic potential distribution within and around the microparticles (i.e., by controlling electronic carrier types through doping) is useful for designing a number of new dynamic systems and devices with precise control over their behaviors.

The Centers for Disease Control and Prevention and Healthy People 2020 call for improvements in meeting men’s reproductive health needs but little is known about the proportion of men in need. This study describes men aged 35 to 39 in need of family planning and preconception care, demographic correlates of these needs, and contraception use among men in need of family planning. Using data from Wave 4 (2008-2010) of the National Survey of Adolescent Males, men were classified in need of family planning and preconception care if they reported sex with a female in the last year and believed that they and their partner were fecund; the former included men who were neither intentionally pregnant nor intending future children and the latter included men intending future children. Men were classified as being in need of both if they reported multiple sex partners in the past year. About 40% of men aged 35 to 39 were in need of family planning and about 33% in need of preconception care with 12% in need of both. Current partner’s age, current union type, and sexually transmitted infection health risk differentiated men in need of family planning and preconception care (all p s < .01) and participants’ race/ethnicity further differentiated men in need of preconception care ( p < .01). More than half of men in need of family planning reported none of the time current partner hormonal use (55%) or condom use (52%) during the past year. This study identified that many men in their mid-30s are in need of family planning or preconception care.

Portable point-of-care (POC) medical diagnostic devices demand low power consumption, efficient use of low sample and reagent volumes, and small size. A “digital” electrowetting-on-dielectric (EWD) microfluidics system with integrated optical sensors is a promising platform for portable POC diagnostic devices that integrate sample preparation with sensing. Herein is reported the highest sensitivity and figure of merit (FOM) microresonator sensor integrated with an EWD system to date [FOM is the product of the quality (Q) factor and the sensitivity (S)]. The EWD system embedded microresonator sensor had a measured FOM of 0.60 × 106 nm/RIU (Q = 8,400, S = 72 nm/RIU) in 2-cSt silicone oil and water, which is nearly double the best FOM previously reported for an microresonator placed on top of an EWD system. Additionally, a nominal FOM of 1.2 × 106 nm/RIU (Q = 15 000, S = 82 nm/RIU) was measured for the vertically coupled sensor fabricated on a standard SiO2/Si substrate. This FOM is the highest reported to date for SU-8 microresonators probed at wavelengths around 1550 nm. These results indicate that high-performance polymer sensors can be integrated with low-power-consumption EWD microfluidics sample preparation systems toward the development of portable POC diagnostic devices.

OBJETIVO: Evaluar la validez y reproducibilidad de un cuestionario autoaplicado de actividad e inactividad física en escolares de 10 a 14 años de la ciudad de México. MATERIAL Y MÉTODOS: Se desarrolló un cuestionario autoaplicado sobre la actividad e inactividad física que se aplicó dos veces a una muestra de 114 estudiantes, de 10 a 14 años de edad, en una población de bajos y medianos ingresos de la ciudad de México, entre mayo y diciembre de 1996. Las madres de los estudiantes llenaron el mismo cuestionario, mientras que aquéllos completaron dos recordatorios de actividad física de 24 horas, que se usaron como criterio de comparación. Se calcularon medidas de tendencia central y de dispersión y se estimó correlación de Pearson. RESULTADOS: Las correlaciones entre las horas al día dedicadas a la actividad e inactividad física del cuestionario de los estudiantes y las de los recordatorios de 24 horas ajustadas por edad, sexo, zona de residencia y enfermedad anterior a la administración del cuestionario fueron de 0.03 para la actividad moderada, de 0.15 para la actividad vigorosa y de 0.51 (p=0.001) para el tiempo dedicado a ver televisión. Al comparar con los recordatorios de 24 horas, el cuestionario sobrestimó el tiempo de ver televisión, leer o participar en actividades vigorosas, y subestimó el tiempo de actividad moderada. Se observaron coeficientes de reproducibilidad en seis meses aceptables para el tiempo de ver televisión (r=0.53), dormir (r=0.40), actividad moderada (r=0.38) y actividad vigorosa (r=0.55) (pOBJECTIVE: To assess the validity and reproducibility of a self-reported questionnaire on physical activity and inactivity, developed for children aged 10-14 in Mexico City. MATERIAL AND METHODS: Between May and December 1996, a self-reported physical activity and inactivity questionnaire was developed and applied twice to a sample of 114 students aged 10 to 14, from a low and middle income population of Mexico City. The children's mothers completed the same questionnaire, and two 24-hour recalls of physical activity were used for comparison. Statistical analysis consisted of central tendency and dispersion measures and Pearson's correlation coefficient. RESULTS: Correlations between hours per day spent in physical activity and inactivity from the children's questionnaire and the 24-hour recall data, were 0.03 for moderate activity, 0.15 for vigorous activity, and 0.51 (p=0.001) for watching television, adjusted by age, gender, town, and illness prior to the administration of the questionnaire. Compared to the 24-hour recall data, the questionnaire overestimated the time spent watching television, reading or participating in vigorous activity, and underestimated the time engaged in moderate activity. Statistically significant (p

A wavelength selection method that combines an inverse Monte Carlo model of reflectance and a genetic algorithm for global optimization was developed for the application of spectral imaging of breast tumor margins. The selection of wavelengths impacts system design in cost, size, and accuracy of tissue quantitation. The minimum number of wavelengths required for the accurate quantitation of tissue optical properties is 8, with diminishing gains for additional wavelengths. The resulting wavelength choices for the specific probe geometry used for the breast tumor margin spectral imaging application were tested in an independent pathology-confirmed ex vivo breast tissue data set and in tissue-mimicking phantoms. In breast tissue, the optical endpoints (hemoglobin, β-carotene, and scattering) that provide the contrast between normal and malignant tissue specimens are extracted with the optimized 8-wavelength set with

Rapid advances in sequencing technologies set the stage for the large-scale medical sequencing efforts to be performed in the near future, with the goal of assessing the importance of rare variants in complex diseases. The discovery of new disease susceptibility genes requires powerful statistical methods for rare variant analysis. The low frequency and the expected large number of such variants pose great difficulties for the analysis of these data. We propose here a robust and powerful testing strategy to study the role rare variants may play in affecting susceptibility to complex traits. The strategy is based on assessing whether rare variants in a genetic region collectively occur at significantly higher frequencies in cases compared with controls (or vice versa). A main feature of the proposed methodology is that, although it is an overall test assessing a possibly large number of rare variants simultaneously, the disease variants can be both protective and risk variants, with moderate decreases in statistical power when both types of variants are present. Using simulations, we show that this approach can be powerful under complex and general disease models, as well as in larger genetic regions where the proportion of disease susceptibility variants may be small. Comparisons with previously published tests on simulated data show that the proposed approach can have better power than the existing methods. An application to a recently published study on Type-1 Diabetes finds rare variants in gene IFIH1 to be protective against Type-1 Diabetes.

The fgui R package is designed for developers of R packages, to help rapidly, and sometimes fully automatically, create a graphical user interface for a command line R package. The interface is built upon the Tcl/Tk graphical interface included in R. The package further facilitates the developer by loading in the help files from the command line functions to provide context sensitive help to the user with no additional effort from the developer. Passing a function as the argument to the routines in the fgui package creates a graphical interface for the function, and further options are available to tweak this interface for those who want more flexibility.

BackgroundPulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532).ResultsAmong NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10(-11)), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10(-10)); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 9 [DBH] (p-value = 9.69 × 10(-9)) and 19 [CYP2A6/7] (p-value = 3.49 × 10(-8)) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10(-9)), 4 [FAM13A] (p-value = 3.88 × 10(-12)), 11 [MMP3/12] (p-value = 3.29 × 10(-10)) and 14 [RIN3] (p-value = 5.64 × 10(-9)).ConclusionsIn a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations.

The article provides information on a study which examined discrepancies in the health history form that incorporated the adverse childhood experiences (ACEs) reported by caregivers on the health history form versus those told to the social workers during therapy. Topics discussed include methodology of the study, ACEs with the greatest change, and limitations of the study.

The field of electrical and computer engineering has evolved significantly in the past two decades. This evolution has broadened the field of ECE, and subfields have seen deep penetration into very specialized areas. Remarkable devices and systems arising from innovative processes, exotic materials, high speed computer simulations, and complex algorithms make ECE an exciting career field. These fascinating developments present greater opportunities for undergraduates to explore the field of ECE as well as greater challenges for them to navigate the curriculum because of the myriad of course and areas of concentration choices they have to make. Reflecting innovations in the field and capitalizing on the collective faculty research expertise, the Department of Electrical and Computer Engineering at Duke University has redesigned its undergraduate curriculum around the theme of "Integrated Sensing and Information Processing." This paper presents details of the ECE curriculum redesign at Duke University including its philosophy and implementation as well as elements of the redesign that are transferable to other universities. Evidence of increased student ability to design a system or component and to work effectively in teams is presented through statistical analyses of student end-of-course course evaluations. Student design project complexity evolution as the curriculum redesign unfolded is also presented, and this provides further evidence that design and teamwork have enhanced student learning throughout the new curriculum.

BackgroundThe genetic risk factors for susceptibility to chronic obstructive pulmonary disease (COPD) are still largely unknown. Additional genetic variants are likely to be identified by genome-wide association studies in larger cohorts or specific subgroups. We sought to identify risk loci for moderate to severe and severe COPD with data from several cohort studies.MethodsWe combined genome-wide association analysis data from participants in the COPDGene study (non-Hispanic white and African-American ethnic origin) and the ECLIPSE, NETT/NAS, and Norway GenKOLS studies (self-described white ethnic origin). We did analyses comparing control individuals with individuals with moderate to severe COPD and with a subset of individuals with severe COPD. Single nucleotide polymorphisms yielding a p value of less than 5 × 10(-7) in the meta-analysis at loci not previously described were genotyped in individuals from the family-based ICGN study. We combined results in a joint meta-analysis (threshold for significance p