Pairwise Fused Lasso

In the last decade several estimators have been proposed that enforce the grouping property. A regularized estimate exhibits the grouping property if it selects groups of highly correlated predictor rather than selecting one representative. The pairwise fused lasso is related to fusion methods but does not assume that predictors have to be ordered. By penalizing parameters and differences between pairs of coefficients it selects predictors and enforces the grouping property. Two methods how to obtain estimates are given. The first is based on LARS and works for the linear model, the second is based on quadratic approximations and works in the more general case of generalized linear models. The method is evaluated in simulation studies and applied to real data sets

Reference values of impulse oscillometric lung function indices in adults of advanced age.

Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. IOS was performed in a population-based sample of 1990 subjects, aged 45-91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5-R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between -1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between -34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction

Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies

BACKGROUND: Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. METHODS: Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF25-75)) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. RESULTS: A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF25-75. Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (</=23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. CONCLUSIONS: Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents

Early age exposure to moisture and mould is related to FeNO at the age of 6 years

Background Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. Methods Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.Peer reviewe

Impact of Residential Green Space on Sleep Quality and Sufficiency in Children and Adolescents Residing in Australia and Germany

Increasing evidence suggests adults living in greener areas tend to have more favourable sleep-related outcomes, but children and adolescents are under-researched. We hypothesised that children and adolescents living in greener areas would have better quality and more sufficient levels of sleep on average, especially within the context of high traffic noise exposure. These hypotheses were tested using multilevel logistic regressions fitted on samples from the nationally representative Longitudinal Study of Australian Children (10-11 years old,n= 3469, and 14-15 years old,n= 2814) and the GINIplus and LISA cohorts (10 years old,n= 1461, and 15 years old,n= 4172) from the Munich, Wesel, and Leipzig areas of Germany. Questionnaire-based binary indicators of sleep sufficiency and sleep quality in each cohort were assessed with respect to objectively measured green space exposures adjusting for age, sex, and maternal education. Models were augmented with proxy measures of traffic noise and two-way interaction terms to test for effect modification. Cross-tabulations illustrated little convincing evidence of association between green space and insufficient sleep or poor sleep quality in either sample, except for insufficient sleep among 10 year old participants in Germany. These null findings were replicated in adjusted models. The proxy for traffic noise was associated with poor quality sleep in 15 year old participants in Germany, but no convincing evidence of modified association with green space was observed

Opinion Cascades and Echo-Chambers in Online Networks: A Proof of Concept Agent-Based Model

In online networks, the polarization of opinions (e.g., regarding presidential elections or referenda) has been associated with the creation of “echo-chambers” of like-minded peers, secluded from those of contrary viewpoints. Previous work has commonly attributed such phenomena to self-regarding preferences (e.g., confirmation bias), individual differences, and the pre-dispositions of users, with clusters forming over repeated interactions. The present work provides a proof of concept Agent-Based Model that demonstrates online networks are susceptible to echo-chambers from a single opinion cascade, due to the spatiotemporal order induced by lateral transmission. This susceptibility is found to vary as a function of degree of interconnectivity and opinion strength. Critically, such effects are found despite globally proportionate levels of opinions, equally rational agents (i.e. absent conformity, confirmation bias or pre-disposition architecture), and prior to cyclical interactions. The assumptions and implications of this work, including the value of Agent-Based Modelling to cognitive psychology, are discussed

Effect of fetal and infant growth on respiratory symptoms in preterm-born children

Objectives: Fetal growth and rapid postnatal weight gain are associated with adverse respiratory outcomes in childhood. However, the preterm-born population is less well studied. We assessed if the increased respiratory symptoms associated with altered fetal growth and infant weight gain were mediated by early factors. Study Design: Weused data from our cohort of preterm- and term-born (n = 4284 and 2865) children, aged 1-10 years. Respiratory outcomes obtained from a respiratory questionnaire were regressed on measures of fetal growth and infant weight gain, defined as >0.67 SD change in fetal measurement or weight between birth and nine months of age, then adjusted for covariates.Weused mediation analysis to investigate which variables were effect modifiers. Results: Accelerated fetal growth between the 1st trimester and birth (OR 2.01; 95%CI 1.25, 2.32), and between the 2nd trimester and birth (1.60; 1.15, 2.22) was associated with increased wheeze-ever in preterm-born children. Rapid infant weight gain was associated with increased wheeze-ever (1.22; 1.02, 1.45); children born ≤32 weeks’ gestation exhibiting rapid weight gain had fivefold higher risk of wheeze-ever compared to term-born without weight gain. Current maternal smoking and gestational age were identified as candidate mediating effects. Conclusions: Our study suggested that antenatal and postnatal growth rates are important for future respiratory health in preterm-born children, and that their effects may be mediated by modifiable factors. Minimizing exposure to environmental pollutants, especially maternal tobacco smoking, may improve outcomes

Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were s