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Intake of sweet and fatty snacks may partly contribute to the occurrence of obesity and other health conditions in childhood. Traditional dietary assessment methods may be limited in accurately assessing the intake of sweet and fatty snacks in children. Metabolite biomarkers may aid the objective assessment of children’s food intake and support establishing diet–disease relationships.

High consumption of ultraprocessed foods (UPFs) continues to draw significant public health interest because of the associated negative health outcomes. Metabolomics can contribute to the understanding of the biological mechanisms through which UPFs may influence health.

The associations of sweetened beverages (SBs) and added sugar (AS) intake with adiposity are still debated. Metabolomics could provide insights into the mechanisms linking their intake to adiposity.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2exposure and perturbation of the microbiome-related pathways.

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation. Linear regression and partial least-squares analyses were conducted for chloroform, brominated THMs, total THMs, and nitrate among controls and for case-control status, together with a N-integration model discriminating colorectal cancer cases from controls through interrogation of correlations between the exposure variables and the metabolomic features. Results revealed a total of 568 metabolomic features associated with at least one water contaminant or colorectal cancer. Annotated metabolites and pathway analysis suggest a number of pathways as potentially involved in the link between exposure to these water contaminants and colorectal cancer, including nicotinamide, cytochrome P-450, and tyrosine metabolism. These findings provide insights into the underlying biological mechanisms and potential biomarkers associated with water contaminant exposure and colorectal cancer risk. Further research in this area is needed to better understand the causal relationship and the public health implications.

Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and untargeted metabolomics are increasingly used in exposome studies to study the interactions between nongenetic factors and the blood metabolome. To reliably and efficiently link detected compounds to exposures and health phenotypes in such studies, it is important to understand the variability in metabolome measures. We assessed the within- and between-subject variability of untargeted LC-HRMS measurements in 298 nonfasting human serum samples collected on two occasions from 157 subjects. Samples were collected ca. 107 (IQR: 34) days apart as part of the multicenter EXPOsOMICS Personal Exposure Monitoring study. In total, 4294 metabolic features were detected, and 184 unique compounds could be identified with high confidence. The median intraclass correlation coefficient (ICC) across all metabolic features was 0.51 (IQR: 0.29) and 0.64 (IQR: 0.25) for the 184 uniquely identified compounds. For this group, the median ICC marginally changed (0.63) when we included common confounders (age, sex, and body mass index) in the regression model. When grouping compounds by compound class, the ICC was largest among glycerophospholipids (median ICC 0.70) and steroids (0.67), and lowest for amino acids (0.61) and the O-acylcarnitine class (0.44). ICCs varied substantially within chemical classes. Our results suggest that the metabolome as measured with untargeted LC-HRMS is fairly stable (ICC > 0.5) over 100 days for more than half of the features monitored in our study, to reflect average levels across this time period. Variance across the metabolome will result in differential measurement error across the metabolome, which needs to be considered in the interpretation of metabolome results.

Microelectromechanical systems accelerometers have opened new possibilities for vibration monitoring of a rotating machinery. They enable mounting accelerometers directly to the rotating component of the machine, e.g., shaft. This enables not only the measurement of a lateral vibration but also a torsional vibration of the machine. This increases the vibration data gathered from the machine by one measurement instrument. This article presents an on-shaft wireless universal measurement unit (UMU) with innovative combination of features, such as a high measurement range and easy mounting. The UMU has a two-sensor configuration where two accelerometers are mounted to the opposite sides of a shaft. This enables to utilize a novel signal processing method to separate torsional and lateral vibration from the data. The signal processing method combines and modifies methods presented in the published literature. The results presented in this article demonstrate that the UMU together with the presented signal processing method can measure frequencies of torsional and lateral vibration accurately. However, the amplitude comparison between the UMU and reference sensors cannot be done adequately because they are measuring either different components of the machine or different physical properties.

Ultrasonic scanning of large spiral bevel gears and the subsequent fracture analyses of early-stage tooth flank fractures imply a mode II crack initiation under surface-parallel, orthogonal shear stresses. An iteration of the Dang Van criterion is presented that focuses exclusively on surface-parallel material planes, yielding a standardizable approach for the study of tooth flank fracture in spiral bevel gears. It is shown that Dang Van’s shear stress amplitude and maximum hydrostatic stress along a surface-perpendicular path can adequately be described by the Hertzian orthogonal shear stress amplitude and Lang’s compressive residual stress. The fatigue properties along the same path are estimated from Thomas’ hardness model and augmented by ISO-inspired lifetime, size and conversion factors. The article closes with a comparison between the commonly used Witzig-Boiadjiev, Hertter-Wirth, DNV subsurface fatigue and the herein proposed, rationalized Dang Van criterion.

Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.

Purpose: High levels of physical activity have been documented in eating disorder patients. Our aim was to examine whether adolescent leisure-time physical activity is prospectively associated with eating disorders in adolescence and young adulthood. Methods: Finnish twins born in 1983–1987 reported their physical activity frequency at ages 12, 14, and 17. A subsample of participants underwent structured, retrospective interviews for eating disorders at the mean age of 22.4 years. Associations between female twins’ physical activity and future eating disorders (571–683 twins/wave) were investigated with the Cox proportional hazards model. To illustrate the physical activity similarity of the co-twins in a twin pair, we used cross-tabulation of eating disorder–discordant twin pairs (13–24 pairs/wave). Results: After adjusting for several covariates, we found no statistically significant longitudinal association between physical activity and eating disorders. This applied when all eating disorders were combined but also when assessed separately as restrictive and non-restrictive eating disorders. Co-twins’ physical activity in adolescence tended to be similar irrespective of their future eating disorder, supporting the results of the regression analysis. Conclusion: We observed no evidence of adolescent physical activity frequency being prospectively associated with eating disorders in female twins. Further longitudinal studies with larger sample sizes and more detailed physical activity data are needed.

Purpose: The association of bulimic symptoms with sensation seeking is uncertain; however, both behaviors have been linked to alcohol problems. We assessed in a longitudinal, community-based setting whether sensation seeking in adolescence is associated with bulimic symptoms in early adulthood, also accounting for alcohol problems. Methods: Finnish men (N= 2000) and women (N= 2467) born between 1974–1979 completed Zuckerman’s sensation seeking scale (SSS) at age 18. Alcohol problems (Malmö-modified Michigan alcoholism screening test (Mm-MAST) and bulimic symptoms [eating disorder inventory-2, bulimia subscale (EDI-Bulimia), population and clinical scoring systems] were defined at age 22–27. We examined relationships between SSS, Mm-MAST, and EDI-Bulimia using Pearson’s correlation coefficient (r) and linear regression. Results: Alcohol problems were moderately correlated with sensation seeking and bulimic symptoms (population scoring) among women and men (r= 0.21–0.31). The correlation between sensation seeking and bulimic symptoms (population scoring) was weak among men (r= 0.06, p= 0.006) and even weaker and non-significant among women (r= 0.03, p= 0.214). Adjustment for alcohol problems removed the association between sensation seeking and bulimic symptoms among men. Furthermore, there were no significant correlations between sensation seeking and bulimic symptoms when assessing EDI-Bulimia clinical scoring. Conclusion: Sensation seeking and bulimic symptoms were not associated among women. The association between sensation seeking and bulimic symptoms among men was entirely attributable to increased alcohol problems among those with higher sensation seeking. While this association may be important on the population level, its clinical significance may be minor. Level of evidence: Level III, well-designed cohort study.

Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NOx, ultrafine particles (UFP), and oxidative potential (OP) of PM2.5on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to −0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.

Birth weight is an important indicator of maternal and fetal health and a predictor of health in later life. However, the determinants of variance in birth weight are still poorly understood. We aimed to identify the biological pathways, which may be perturbed by environmental exposures, that are important in determining birth weight. We applied untargeted mass-spectrometry-based metabolomics to 481 cord blood samples collected at delivery in four birth cohorts from across Europe: ENVIRONAGE (Belgium), INMA (Spain), Piccolipiu (Italy), and Rhea (Greece). We performed a metabolome-wide association scan for birth weight on over 4000 metabolic features, controlling the false discovery rate at 5%. Annotation of compounds was conducted through reference to authentic standards. We identified 68 metabolites significantly associated with birth weight, including vitamin A, progesterone, docosahexaenoic acid, indolelactic acid, and multiple acylcarnitines and phosphatidylcholines. We observed enrichment (p< 0.05) of the tryptophan metabolism, prostaglandin formation, C21-steroid hormone signaling, carnitine shuttle, and glycerophospholipid metabolism pathways. Vitamin A was associated with both maternal smoking and birth weight, suggesting a mediation pathway. Our findings shed new light on the pathways central to fetal growth and will have implications for antenatal and perinatal care and potentially for health in later life.

ABSTRACTEndogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby Pvalues. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes. Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

In this paper, the problem of estimating unknown propeller torque excitations and angular velocities in an azimuth-thruster driveline is considered. A dynamical model of the driveline has been derived and is used to construct a fixed-lag Kalman-filter-type smoother for estimating the propeller torque from indirect measurements. The proposed method has been validated in a simulation case study.

Research in eating disorders in males has been active lately compared to the past. This review aims to provide an overview of the recently published studies of eating disorders in males.

Androgens are key factors involved in the development and progression of prostate cancer (PCa), and PCa growth can be suppressed by androgen deprivation therapy. In a considerable proportion of men receiving androgen deprivation therapy, however, PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies challenging. We used an orthotopic VCaP human PCa xenograft model to study cellular and molecular changes in tumors after androgen deprivation therapy (castration). Tumor growth was monitored through weekly serum prostate-specific antigen measurements, and mice with recurrent tumors after castration were randomized to treatment groups. Serum prostate-specific antigen concentrations showed significant correlation with tumor volume. Castration-resistant tumors retained concentrations of intratumoral androgen (androstenedione, testosterone, and 5α-dihydrotestosterone) at levels similar to tumors growing in intact hosts. Accordingly, castration induced up-regulation of enzymes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. The AR antagonists enzalutamide (MDV3100) and ARN-509 suppressed PSA production of castration-resistant tumors, confirming the androgen dependency of these tumors. Taken together, the findings demonstrate that our VCaP xenograft model exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC.

Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome‐wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive‐Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self‐report questionnaires completed by the TwinsUK population‐based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed‐up signals from various strata using a two‐stage replication strategy in two independent cohorts of European ancestry. We meta‐analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive‐Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED‐related phenotypes, we detected association of eight genetic variants with P< 10−5. Genetic variants that showed suggestive evidence of association were previously associated with several psychiatric disorders and ED‐related phenotypes. Our study indicates that larger‐scale collaborative studies will be needed to achieve the necessary power to detect loci underlying ED‐related traits. © 2012 Wiley Periodicals, Inc.

In a power plant a fire cell forms the basic subunit. Since the fire is initially located there, the full-scale time dependent fire simulation and estimation of target response must be performed within the fire cell. Conditional, time dependent damage probabilities in a fire cell can now be calculated for arbitrary targets (component or a subsystem) combining probabilistic (Monte Carlo) and deterministic simulation. For the latter a spectrum from simple correlations up to latest computational fluid dynamics models is available. Selection of the code is made according to the requirements from the target cell. Although calculations are numerically heavy, it is now economically possible and feasible to carry out quantitative fire-PSA for a complete plant iteratively with the main PSA. From real applications examples are shown on assessment of fire spread possibility in a relay room, and potential of fire spread on cables in a tunnel.

AbstractIn the population-based FinnTwin16study, proportions of genetic and environmental factors contributing to muscle dissatisfaction and muscle-enhancing substance use were assessed in 319 pairs of twin brothers: 141 monozygotic (MZ) and 178 dizygotic (DZ) pairs. In addition there were 86 twin individuals from pairs in which only one co-twin responded. Of all respondents, 30% experienced high muscle dissatisfaction. The corresponding proportion of muscle-enhancing substance use was 10%. The subjects were similar in age (23.8 years, 95% confidence interval [CI] 23.76?23.84), body mass index (23.7, 95% CI 23.5?23.9), and waist circumference (84.5 cm, 95% CI 83.7?85.2), independent of their muscle dissatisfaction or muscle-enhancing substance use status and independent of their zygosity. The MZ polychoric correlation for muscle dissatisfaction was .39 (95% CI .17?.58) and .27 for DZ pairs (95% CI .07?.46). The MZ tetrachoric correlation for muscle-enhancing substance use was .65 (95% CI .28?.87) and .56 for DZ pairs (95% CI .26?.78). The AE model, where additive genetic factors (A) accounted for 42% (95% CI .23?.59) and unique environmental factors (E) 58% (95% CI .41?.77) of the liability, provided the best fit for muscle dissatisfaction. The CE model, where common environmental factors (C) accounted for 60% (95% CI .37?.77) and unique environmental factors (E) 40% (95% CI .23?.63) of the liability, provided the best fit for muscle-enhancing substance use. Both genetic and unique (nonfamilial) environmental factors are involved in muscle dissatisfaction in the population. Nongenetic factors (both familial and non-familial) appear to best explain the use of muscle-enhancing substances.

Objective: To explore eating styles associated with intentional weight loss (IWL) and to determine whether the genetic liability in IWL is entirely shared with genetic liability affecting BMI. Research Methods and Procedures: As part of a longitudinal assessment of various health‐related behaviors in a large population‐based sample of twins, eating styles, BMI, and the number of times the study participants had intentionally lost ≥5 kg were assessed by questionnaire from 4667 male and female twins (22 to 27 years of age). Associations of eating styles and IWL were explored using polytomous logistic regression models adjusted for BMI. Sex‐specific bivariate structural equation modeling was used to explore genetic and environmental correlations of BMI and IWL. Results: Individuals who had engaged in IWL exhibited markedly more restricting, overeating, and alternating restricting/overeating than those in the no‐IWL group. Snacking and eating in the evening were characteristic of women with at least two IWL attempts. Eating in response to visual and emotional cues was very pronounced in women who had engaged in IWL but much less so in men. IWL was estimated to have a heritability of 38% [95% confidence interval (CI), 19% to 55%] in men and 66% (95% CI, 55% to 75%) in women. The genetic covariance of BMI and IWL was 0.38 (95% CI, 0.28 to 0.47) for men and 0.45 (95% CI, 0.41 to 0.52) for women. Discussion: Distinct sex differences exist in eating styles associated with IWL and in the heritability of IWL. Most genetic factors affecting BMI are different from those affecting IWL.

Ignition frequencies and ignition frequencies per floor area were determined for different building categories in Finland as total groups and as a function of the floor area of the building. These frequencies are needed as input for risk analysis using performance based fire safety design. It was found that differences between building categories or location within country were so small that a universal curve for the whole country could be determined. For ignition frequency per floor area for small buildings a strong dependence on size is observed, but it remains approximately constant for larger buildings. Additionally periodical variations of ignition frequency of buildings by month and week of year, day of week, and time of day were determined. Historical review of the development of ignition frequency models was made. Some evaluation on the generality of the results was made based on the theoretical models.

A systems approach to fire safety is a way to evaluate fire safety of buildings, especially large and complex buildings. One tool for building fire risk analysis is the computer programme FIRE (Fire Simulation Program) de veloped at Worcester Polytechnic Institute (WPI) in USA by Professor R. Fitz gerald and his group. The computational utility of the code was improved and adapted to the Finnish environment by Technical Research Centre of Finland (VTT) and two engineering consultants, Rakennus-Ekono and LCA-Engin eering.We simulated fires in a four-floor building where one wing (single fire com partment) was selected for simulation. We chose four representative room types in the building for which fire engineering data were selected. By simulation, we studied the impact of different design alternatives to fire risk of the total building. Fire risk in each design alternative was computed as expectation of loss. Costs caused by structural changes and active fire safety systems were taken into account. The compilations proved that it is possible to design differently from the current fire code and still reduce the fire risk level. FIRE does not yet support the evaluation of life safety, but the results can be used for that purpose indirectly.

Hepatocellular carcinoma (HCC) is characterised by increasing incidence, late diagnosis and high mortality rates. Changes in liver metabolism during HCC development may alter circulating metabolite levels, which could be identified years before HCC diagnosis. Also, a detailed understanding of metabolic dysfunction in HCC may lead to the identification of better prevention strategies. In this context, we aimed to characterise pre-diagnostic circulating biomarkers of HCC risk using an LC-MS untargeted metabolomics approach.