Robust Sure Independence Screening for Non-polynomial dimensional Generalized Linear Models

We consider the problem of variable screening in ultra-high dimensional (of non-polynomial order) generalized linear models (GLMs). Since the popular SIS approach is extremely unstable in the presence of contamination and noises, which may frequently arise in the large scale sample data (e.g., Omics data), we discuss a new robust screening procedure based on the minimum density power divergence estimator (MDPDE) of the marginal regression coefficients. Our proposed screening procedure performs extremely well both under pure and contaminated data scenarios. We also theoretically justify the use of this marginal MDPDEs for variable screening from the population as well as sample aspects; in particular, we prove that these marginal MDPDEs are uniformly consistent leading to the sure screening property of our proposed algorithm. We have also proposed an appropriate MDPDE based extension for robust conditional screening in the GLMs along with the derivation of its sure screening property.Comment: Work in Progres

Robust sure independence screening for nonpolynomial dimensional generalized linear models

We consider the problem of variable screening in ultra-high-dimensional generalized linear models (GLMs) of nonpolynomial orders. Since the popular SIS approach is extremely unstable in the presence of contamination and noise, we discuss a new robust screening procedure based on the minimum density power divergence estimator (MDPDE) of the marginal regression coefficients. Our proposed screening procedure performs well under pure and contaminated data scenarios. We provide a theoretical motivation for the use of marginal MDPDEs for variable screening from both population as well as sample aspects; in particular, we prove that the marginal MDPDEs are uniformly consistent leading to the sure screening property of our proposed algorithm. Finally, we propose an appropriate MDPDE-based extension for robust conditional screening in GLMs along with the derivation of its sure screening property. Our proposed methods are illustrated through extensive numerical studies along with an interesting real data application

Dietary Predictors and Plasma Concentrations of Perfluorinated Compounds in a Coastal Population from Northern Norway

Dietary intake, age, gender, and body mass index were investigated as possible predictors of perfluorinated compounds in a study population from northern Norway (44 women and 16 men). In addition to donating a blood sample, the participants answered a detailed questionnaire about diet and lifestyle. Perfluorooctane sulfonate (PFOS) (29 ng/mL), perfluorooctanoate (PFOA) (3.9 ng/mL), perfluorohexane sulfonate (PFHxS) (0.5 ng/mL), perfluorononanoate (PFNA) (0.8 ng/mL), and perfluoroheptane sulfonate (PFHpS) (1.1 ng/mL) were detected in more than 95% of all samples. Of the dietary items investigated, fruit and vegetables significantly reduced the concentrations of PFOS and PFHpS, whereas fatty fish to a smaller extent significantly increased the levels of the same compounds. Men had significantly higher concentrations of PFOS, PFOA, PFHxS, and PFHpS than women. There were significant differences in PFOS isomer pattern between genders, with women having the largest proportion of linear PFOS. PFOS, PFHxS, and PFHpS concentrations also increased with age

Time trends of perfluoroalkyl substances in blood in 30-year old Norwegian men and women in the period 1986–2007

Biomonitoring studies are helpful tools and can increase our knowledge on time trends in human blood concentrations of PFASs: how they relate to emission trends and the potential prenatal exposure for future generations. In this study, serum was sampled in cross-sections of men and women who were 30 years old in each of the years 1986, 1994, 2001, and 2007 in Northern Norway and analyzed for 23 PFASs. Differences in serum concentrations across sampling years were investigated graphically and with significance testing and compared with those observed in our previous longitudinal study using repeated individual measurements in older men in the same years. The results demonstrate overall increasing blood burdens of PFASs in men and women in reproductively active ages during 1986–2001 and decreases until 2007. However, longer chained PFASs were still increasing in 2007 indicating divergent time trends between the different PFASs, underlining the importance of continued biomonitoring. Comparisons between 30-year-old men and older men within the same population demonstrated variation in time trends in the exact same years, underlining that biomonitoring studies must regard historic exposures and birth cohort effects

Indications of decreasing human PTS concentrations in North West Russia

The Russian Arctic covers an enormous landmass with diverse environments. It inhabits more than 20 different ethnic groups, all of them with various living conditions and food traditions. Indigenous populations with a traditional way of living are exposed to a large number of anthropogenic pollutants, such as persistent organic pollutants (POPs) and toxic metals, mainly through the diet. Human monitoring of persistent organic pollutants (POPs) and heavy metals in the Russian Arctic has only been performed on irregular intervals over the past 15 years, thus, there is still a lack of baseline data from many ethnic groups and geographical regions. The aim of the current study was to investigate concentrations of POPs and toxic metals in three groups of indigenous people from the Russian Arctic. Plasma concentrations of POPs were measured in one of the locations (Nelmin-Nos) in 2001–2003 which gave the unique opportunity to compare concentrations over time in a small Russian arctic community. During 2009 and early 2010, 209 blood samples were collected from three different study sites in North West Russia; Nelmin-Nos, Izhma and Usinsk. The three study sites are geographically separated and the inhabitants are expected to have different dietary habits and living conditions. All blood samples were analyzed for POPs and toxic metals. PCB 153 was present in highest concentrations of the 18 PCBs analyzed. p,p′-DDE and HCB were the two most dominating OC pesticides. Males had higher concentrations of PCB 138, 153 and 180 than women and age was a significant predictor of PCB 153, 180, HCB and p,p′-DDD. Males from Izhma had significantly higher concentrations of HCB than males from the other study sites and women from Usinsk had higher concentrations of p,p′-DDE. Parity was a significant predictor of p,p′-DDE. Hg and Pb concentrations increased with increasing age and males had significantly higher concentrations of Pb than women. The study group from Izhma had significantly higher concentrations of Cd when controlling for age and gender and the study group from Usinsk had higher concentrations of Se than the others. Compared to the results from Nelmin-Nos in 2001–2003, a clear decrease in p,p′-DDE concentrations for both women and men was observed. The current study indicates a significant reduction of several PTSs in human blood samples from North West Russia over the past 10 years

Space Weather impact on the degradation of NOAA POES MEPED proton detectors

The Medium Energy Proton and Electron Detector (MEPED) on board the National Oceanic and Atmospheric Administration Polar Orbiting Environmental Satellites (NOAA POES) is known to degrade with time. In recent years a lot of effort has been put into calibrating the degraded proton detectors. We make use of previous work and show that the degradation of the detectors can be attributed to the radiation dose of each individual instrument. However, the effectiveness of the radiation in degrading the detector is modulated when it is weighted by the mean $\textit{ap}$ index, increasing the degradation rate in periods with high geomagnetic activity, and decreasing it through periods of low activity. When taking $\textit{ap}$ and the radiation dose into account, we find that the degradation rate is independent of spacecraft and detector pointing direction. We have developed a model to estimate the correction factor for all the MEPED detectors as a function of accumulated corrected flux and the $\textit{ap}$ index. We apply the routine to NOAA POES spacecraft starting with NOAA-15, including the European satellites MetOp-02 and MetOp-01, and estimate correction factors

Combined Lifestyle Behaviors and the Incidence of Common Cancer Types in the Norwegian Women and Cancer Study (NOWAC)

Introduction: Only a small number of studies have examined the impact of combined lifestyle behaviors on cancer incidence, and never in a Norwegian population. Purpose: To examine linear and nonlinear associations of combined lifestyle factors, assessed through a healthy lifestyle index (HLI), with the incidence of postmenopausal breast, colorectal, lung, postmenopausal endometrial, postmenopausal ovarian, pancreatic, and kidney cancer among women in Norway. Methods: This prospective study included 96,869 women enrolled in the Norwegian Women and Cancer (NOWAC) cohort. Baseline information on lifestyle factors was collected between 1996 and 2004. The HLI was constructed from five lifestyle factors: physical activity level, body mass index, smoking, alcohol consumption, and diet. Each factor contributed 0 to 4 points to the HLI score, which ranged from 0 to 20, with higher scores representing a healthier lifestyle. Multiple imputation was used to handle missing data. Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Restricted cubic splines were used to examine nonlinearity in the associations. Results: The HRs for a one-point increment on the HLI score were 0.97 (95% CI: 0.96– 0.98) for postmenopausal breast cancer, 0.98 (0.96– 1.00) for colorectal cancer, 0.86 (0.84– 0.87) for lung cancer, 0.93 (0.91– 0.95) for postmenopausal endometrial cancer, 0.99 (0.96– 1.02) for postmenopausal ovarian cancer, 0.92 (0.89– 0.95) for pancreatic cancer, and 0.94 (0.91– 0.97) for kidney cancer. Nonlinearity was observed for the inverse associations between HLI score and the incidence of lung cancer and postmenopausal breast cancer. Conclusion: Based on our results, healthier lifestyle, as assessed by the HLI score, was associated with lower incidence of postmenopausal breast, colorectal, lung, postmenopausal endometrial, pancreatic, and kidney cancer among women, although the magnitude and linearity varied. Adoption of healthier lifestyle behaviors should be a public health priority to reduce the cancer burden among Norwegian women

Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach

Accepted manuscript version. Published version available at https://doi.org/10.1016/j.envint.2015.01.007. Accepted manuscript version, licensed CC BY-NC-ND 4.0.The mechanisms involved in thyroid homeostasis are complex, and perfluoroalkyl substances (PFASs) have been indicated to interfere at several levels in this endocrine system. Disruption of the maternal thyroid homeostasis during early pregnancy is of particular concern, where subclinical changes in maternal thyroid hormones (THs) may affect embryonic and foetal development. The present study investigated associations between THs, thyroid binding proteins (TH-BPs) and PFAS concentrations in pregnant women from Northern Norway. Women participating in The Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood sample at three visits related to their pregnancy and postpartum period (during the second trimester, 3 days and 6 weeks after delivery) in the period 2007–2009. Participants were assigned to quartiles according to PFAS concentrations during the second trimester and mixed effects linear models were used to investigate potential associations between PFASs and repeated measurements of THs, TH-BPs, thyroxin binding capacity and thyroid peroxidase antibodies (anti-TPOs). Women within the highest perfluorooctane sulfonate (PFOS) quartile had 24% higher mean concentrations of thyroid stimulating hormone (TSH) compared to the first quartile at all sampling points. Women within the highest quartiles of perfluorodecanoate (PFDA) had 4% lower mean concentrations of triiodothyronine (T3) and women within the highest quartile of perfluoroundecanoate (PFUnDA) had 3% lower mean concentrations of free triiodothyronine (FT3). Further, the difference in concentrations and the changes between three time points were the same for the PFAS quartiles. Thyroxin binding capacity was associated with all the THs and TH-BPs, and was selected as a holistic adjustment for individual changes in TH homeostasis during pregnancy. Finally, adjusting for maternal iodine status did not influence the model predictions. Findings in the present study suggest modifications of TH homeostasis by PFASs in a background exposed maternal population. The variation in levels of THs between PFAS quartiles was within normal reference ranges and may not be of clinical significance in the pregnant woman. However, subtle individual changes in maternal THs may have significant consequences for foetal health

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Persistent Organic Pollutants and the Association with Maternal and Infant Thyroid Homeostasis: A Multipollutant Assessment

Source: doi: 10.1289/EHP152.Reproduced with permission from Environmental Health Perspectives.Background:Disruption of thyroid homeostasis has been indicated in human studies targeting effects of persistent organic pollutants (POPs). Influence on the maternal thyroid system by POPs is of special interest during pregnancy because such effects could impair infant thyroid homeostasis. Objectives:We investigated the association between POPs and thyroid-stimulating hormone (TSH) and thyroid hormones (THs) in mother and child pairs from the Northern Norway Motherand- Child Contaminant Cohort Study (MISA). Methods:Nineteen POPs and 10 thyroid parameters were analyzed in serum from 391 pregnant women in their second trimester. In addition, TSH concentrations in heel-prick samples from the infants were analyzed by the Norwegian Newborn Screening program. Association studies with a multipollutant approach were performed using multivariate analyses; partial least squares (PLS) regression, hierarchical clustering, and principal component analysis (PCA). Results:Several POPs were significantly associated with TSH and THs: a) PFOS was positively associated with TSH; b) PCBs, HCB, and nonachlors were inversely associated with T3, T4, and FT4; and, c) PFDA and PFUnDA were inversely associated with T3 and FT3. After mutual adjustments for the other contaminants, only PFDA and PFUnDA remained significantly associated with T3 and FT3, respectively. Infants born to mothers within the highest TSH quartile had 10% higher mean concentrations of TSH compared with children born to mothers in the lowest TSH quartile. Conclusion:The present results suggest that background exposures to POPs can alter maternal thyroid homeostasis. This research contributes to the understanding of multipollutant exposures using multivariate statistical approaches and highlights the complexity of investigating environmental concentrations and mixtures in regard to maternal and infant thyroid function