A heavy-tailed model for analyzing miRNA-seq raw read counts.

This article addresses the limitations of existing statistical models in analyzing and interpreting highly skewed miRNA-seq raw read count data that can range from zero to millions. A heavy-tailed model using discrete stable distributions is proposed as a novel approach to better capture the heterogeneity and extreme values commonly observed in miRNA-seq data. Additionally, the parameters of the discrete stable distribution are proposed as an alternative target for differential expression analysis. An R package for computing and estimating the discrete stable distribution is provided. The proposed model is applied to miRNA-seq raw counts from the Norwegian Women and Cancer Study (NOWAC) and the Cancer Genome Atlas (TCGA) databases. The goodness-of-fit is compared with the popular Poisson and negative binomial distributions, and the discrete stable distributions are found to give a better fit for both datasets. In conclusion, the use of discrete stable distributions is shown to potentially lead to more accurate modeling of the underlying biological processes.

penalizedclr: an R package for penalized conditional logistic regression for integration of multiple omics layers.

BACKGROUND: The matched case-control design, up until recently mostly pertinent to epidemiological studies, is becoming customary in biomedical applications as well. For instance, in omics studies, it is quite common to compare cancer and healthy tissue from the same patient. Furthermore, researchers today routinely collect data from various and variable sources that they wish to relate to the case-control status. This highlights the need to develop and implement statistical methods that can take these tendencies into account. RESULTS: We present an R package penalizedclr, that provides an implementation of the penalized conditional logistic regression model for analyzing matched case-control studies. It allows for different penalties for different blocks of covariates, and it is therefore particularly useful in the presence of multi-source omics data. Both L1 and L2 penalties are implemented. Additionally, the package implements stability selection for variable selection in the considered regression model. CONCLUSIONS: The proposed method fills a gap in the available software for fitting high-dimensional conditional logistic regression models accounting for the matched design and block structure of predictors/features. The output consists of a set of selected variables that are significantly associated with case-control status. These variables can then be investigated in terms of functional interpretation or validation in further, more targeted studies.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.

Euthanasia of animals - association with veterinarians' suicidal thoughts and attitudes towards assisted dying in humans: a nationwide cross-sectional survey (the NORVET study).

BACKGROUND: Veterinarians are an occupational group with an increased suicide risk. Euthanasing animals may influence both veterinarians' views on assisted dying in humans and their suicide risk. We investigated (I) attitudes towards assisted dying, (II) whether the field of work and the frequency of euthanasing animals were associated with positive attitudes towards human euthanasia, and (III) whether frequently euthanasing animals was associated with serious suicidal thoughts. METHODS: We conducted a nationwide cross-sectional study among veterinarians in Norway (response rate: 75%). Logistic regression models were used to calculate the odds ratios for both positive attitudes towards human euthanasia and serious suicidal thoughts. The analyses were adjusted for socio-demographic and work-related factors. RESULTS: Fifty-five percent of the veterinarians agreed that euthanasia should be permitted for humans with a fatal disease and short life expectancy. Working with companion animals was independently associated with positive attitudes towards human euthanasia (OR = 1.66 (95% CI: 1.23-2.23)), while veterinarians' frequency of euthanasing animals was not. Frequency of euthanasing animals was independently associated with serious suicidal thoughts, OR = 2.56 (95% CI: 1.35-4.87). CONCLUSIONS: Veterinarians' attitudes towards assisted dying in humans did not differ from those of the general population. Veterinarians' frequency of euthanasing animals was not associated with positive attitudes towards euthanasia in humans. However, veterinarians working in companion animal practices were more likely to have positive attitudes towards euthanasia in humans. Moreover, euthanising animals five times or more a week was associated with serious suicidal thoughts. We need more research to infer about causality in these findings.

Does the association between adiposity measures and pre-frailty among older adults vary by social position? Findings from the Tromsø study 2015/2016.

INTRODUCTION: Pre-frailty provides an ideal opportunity to prevent physical frailty and promote healthy ageing. Excess adiposity has been associated with an increased risk of pre-frailty, but limited studies have explored whether the association between adiposity measures and pre-frailty varies by social position. METHODS: We used data from the seventh survey of the Tromsø Study (Tromsø7) conducted in 2015-2016. Our primary sample consisted of 2,945 women and 2,794 men aged ≥ 65 years. Pre-frailty was defined as the presence of one or two of the five frailty components: low grip strength, slow walking speed, exhaustion, unintentional weight loss and low physical activity. Adiposity was defined by body mass index (BMI), waist circumference (WC), fat mass index (FMI) and visceral adipose tissue (VAT) mass. Education and subjective social position were used as measures of social position. Poisson regression with robust variance was used to assess the association between adiposity measures and pre-frailty, and the interaction term between adiposity measures and social position measures were utilised to explore whether the association varied by social position. RESULTS: In our sample, 28.7% of women and 25.5% of men were pre-frail. We found sub-multiplicative interaction of BMI-defined obesity with education in women and subjective social position in men with respect to development of pre-frailty. No other adiposity measures showed significant variation by education or subjective social position. Regardless of the levels of education or subjective social position, participants with excess adiposity (high BMI, high WC, high FMI and high VAT mass) had a higher risk of pre-frailty compared to those with low adiposity. CONCLUSION: We consistently observed that women and men with excess adiposity had a greater risk of pre-frailty than those with low adiposity, with only slight variation by social position. These results emphasize the importance of preventing excess adiposity to promote healthy ageing and prevent frailty among all older adults across social strata.

Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Numerous intrauterine factors may affect the offspring's growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. METHODS: This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). RESULTS: Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). CONCLUSIONS: Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Fish intake and pre-frailty in Norwegian older adults - a prospective cohort study: the Tromsø Study 1994-2016.

BACKGROUND: Pre-frailty is an intermediate, potentially reversible state before the onset of frailty. Healthy dietary choices may prevent pre-frailty. Fish is included in most healthy diets, but little is known about the association between long-term habitual fish intake and pre-frailty. We aimed to elucidate the longitudinal association between the frequency of fish intake and pre-frailty in a cohort of older adults in Norway. METHODS: 4350 participants (52% women, ≥65 years at follow-up) were included in this prospective cohort study. Data was obtained from three waves of the population-based Tromsø Study in Norway; Tromsø4 (1994-1995), Tromsø6 (2007-2008) and Tromsø7 (follow-up, 2015-2016). Frailty status at follow-up was defined by a modified version of Fried's phenotype. Fish intake was self-reported in the three surveys and assessed as three levels of frequency of intake: low (0-3 times/month), medium (1-3 times/week) and high (≥ 4 times/week). The fish-pre-frailty association was analysed using multivariable logistic regression in two ways; (1) frequency of intake of lean, fatty and total fish in Tromsø6 and pre-frailty at follow-up, and (2) patterns of total fish intake across the three surveys and pre-frailty at follow-up. RESULTS: At follow-up, 28% (n = 1124) were pre-frail. Participants with a higher frequency of lean, fatty and total fish intake had 28% (odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.53, 0.97), 37% (OR = 0.63, 95% CI = 0.43, 0.91) and 31% (OR = 0.69, 95% CI = 0.52, 0.91) lower odds of pre-frailty 8 years later compared with those with a low intake, respectively. A pattern of stable high fish intake over 21 years was associated with 41% (OR = 0.59, 95% CI = 0.38, 0.91) lower odds of pre-frailty compared with a stable low intake. CONCLUSIONS: A higher frequency of intake of lean, fatty and total fish, and a pattern of consistent frequent fish intake over time, were associated with lower odds of pre-frailty in older community-dwelling Norwegian adults. These results emphasise the important role of fish in a healthy diet and that a frequent fish intake should be promoted to facilitate healthy ageing.

Professional help-seeking behaviour for mental health problems among veterinarians in Norway: a nationwide, cross-sectional study (The NORVET study).

BACKGROUND: Veterinarians have a relatively high prevalence of mental health problems; however, research on professional help-seeking is limited. The main purpose of the present study was to investigate the prevalence of mental health problems and professional help-seeking behaviour for such problems, and the independent factors associated with help-seeking behaviour among veterinarians in Norway. METHOD: This cross-sectional study included all veterinarians in Norway (response rate 75%, 70% women). Logistic regression was used to calculate odds ratios (OR) for professional help-seeking for mental health problems. Analyses were controlled for socio-demographic, individual (personality trait reality weakness, SCL-5, attitudes toward mental illness), and work-related factors (work field, job stress). RESULTS: The prevalence of self-reported mental health problems in need of treatment was 30% (746/2494), significantly higher among women than men (36% vs. 15%). Fifty-four percent had sought professional help, women significantly more often (56%) than men (41%). Among veterinarians with serious suicidal thoughts, 50% (69/139) had sought help. Veterinarians most frequently related mental health problems to work problems (47%), women significantly more often (49%) than men (34%). Factors significantly associated with help-seeking were being female, OR = 2.11 (95% CI: 1.24-3.60), working with production animals, OR = 0.35 (0.13-0.98), public administration, OR = 2.27 (1.15-4.45), academia/research, OR = 4.78 (1.99-11.47) or 'other' fields, OR = 2.79 (1.23-6.32), and attitudes toward mental illness, OR = 1.32 (1.03-1.68). CONCLUSIONS: Thirty percent of veterinarians in Norway reported mental health problems in need of treatment, and only half of them had sought professional help. A low degree of help-seeking was also seen among those with serious suicidal thoughts. Being female, positive attitudes toward treatment of mental illness, working in public administration, academia/research and 'other' field were associated with more help-seeking, while working in production animal practice was associated with less help-seeking. Interventions to increase help-seeking behaviour for mental health problems among veterinarians are warranted.

Mortality, Causes of Death, and Predictors of Death among Patients On and Off Opioid Agonist Treatment: Results from a 19-Year Cohort Study.

BACKGROUND: Mortality is increased among people with opioid use disorder but reduced while on opioid agonist treatment (OAT). However, the impact of patient and treatment characteristics on mortality and causes of death is insufficiently studied. OBJECTIVES: The objective of this study was to explore mortality and causes of death and examine the impact of patient and treatment characteristics on mortality in an OAT cohort with high retention in treatment. METHODS: Design: longitudinal cohort study. SETTING: Norway. Observation period: time from OAT start as of 1998 until death or end of 2016, 2,508 person-years (PY) in total. SAMPLE: 200 persons starting OAT 1998-2007. DATA SOURCES: hospital records, interviews, the Norwegian Cause of Death Registry, Statistics Norway. RESULTS: Retention: 86.4% of the observation period was on OAT, 9.0% off, 4.6% unknown OAT status. All-cause crude mortality rate per 100 PY during the whole observation period was 1.64 (95% CI: 1.19-2.20), for deaths of somatic cause 0.88 (0.56-1.31), for drug-induced deaths 0.44 (0.23-0.76), and traumatic deaths 0.24 (0.10-0.50). Off-versus-on-OAT all-cause mortality ratio was 2.31 (1.00-4.85). On OAT, 58% of the deaths were of somatic cause and 21% drug-induced; off OAT, 38% of somatic cause and 50% drug-induced. Increasing baseline age and rate of somatic hospital treatment episodes were independently associated with increased all-cause mortality risk, while increasing rate of in-patient psychiatric treatment episodes was associated with reduced risk. Increasing duration of nicotine and cannabis use and alcohol dependence as well as increasing severity of polydrug use were associated with increased all-cause and somatic mortality adjusted for age and sex. CONCLUSION: The long observation period made it possible to demonstrate the importance of long-term retention in OAT to reduce mortality. Further, the preponderance of somatic and reduction of drug-induced causes of death during OAT underlines the need for follow-up of chronic diseases and health-promoting lifestyle changes. These findings add to the knowledge about long-term OAT effects, not least in ageing OAT populations.

On optimal two-stage testing of multiple mediators.

Mediation analysis in high-dimensional settings often involves identifying potential mediators among a large number of measured variables. For this purpose, a two-step familywise error rate procedure called ScreenMin has been recently proposed. In ScreenMin, variables are first screened and only those that pass the screening are tested. The proposed data-independent threshold for selection has been shown to guarantee asymptotic familywise error rate. In this work, we investigate the impact of the threshold on the finite-sample familywise error rate. We derive a power maximizing threshold and show that it is well approximated by an adaptive threshold of Wang et al. (2016, arXiv preprint arXiv:1610.03330). We illustrate the investigated procedures on a case-control study examining the effect of fish intake on the risk of colorectal adenoma. We also apply our procedure in the context of replicability analysis to identify single nucleotide polymorphisms (SNP) associated with crop yield in two distinct environments.

Integrative, multi-omics, analysis of blood samples improves model predictions: applications to cancer.

BACKGROUND: Cancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific ("individual") patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as "shared" or "joint". In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case-control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case-control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas. RESULTS: Our results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development. CONCLUSIONS: In the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.

Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements.

BACKGROUND: Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health. METHOD/DESIGN: Men and women (calculated sample size = 60), aged 18-45 years, with body mass index of 27-35 kg/m2 will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAAhigh, total diet SAA ~ 50-60 mg/kg body weight/day; SAAlow, total diet SAA ~ 15-25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation. DISCUSSION: The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders. Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021.

A population-based study of testicular cancer risk among children and young adults from Norway and Utah, USA.

Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951-2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980-1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68-17.16) and 6.02 (95% CI 4.80-7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78-22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations.

Multi-insight visualization of multi-omics data via ensemble dimension reduction and tensor factorization.

MOTIVATION: Visualization of high-dimensional data is an important step in exploratory data analysis and knowledge discovery. However, it is challenging, because the interpretation is highly subjective. If we see dimensionality reduction (DR) techniques as the main tool for data visualization, they are like multiple cameras that look into the data from different perspectives or angles. We can hardly prescribe one single perspective for all datasets and problems. One snapshot of data cannot reveal all the relevant aspects of the data in higher dimensions. The reason is that each of these methods has its own specific strategy, normally based on well-established mathematical theories to obtain a low-dimensional projection of the data, which sometimes is totally different from the others. Therefore, relying only on one single projection can be risky, because it can close our eyes to important parts of the full knowledge space. RESULTS: We propose the first framework for multi-insight data visualization of multi-omics data. This approach, contrary to single-insight approaches, is able to uncover the majority of data features through multiple insights. The main idea behind the methodology is to combine several DR methods via tensor factorization and group the solutions into an optimal number of clusters (or insights). The experimental evaluation with low-dimensional synthetic data, simulated multi-omics data related to ovarian cancer, as well as real multi-omics data related to breast cancer show the competitive advantage over state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: https://folk.uio.no/hadift/MIV/ [user/pass via hadift@medisin. uio.no]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population-based study in Utah and Norway.

BACKGROUND: In this study, we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumors in the central nervous system (CNS), and leukemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. METHODS: We used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. RESULTS: The overall incidence of CNS tumors increased with consecutive birth cohorts similarly in Utah and Norway (both P < 0.001). Incidence rates of leukemia were more stable and similar in both Utah and in Norway with 4.6/100 000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumors was significantly associated with risk of childhood CNS tumors in Utah HR = 3.05 (95% CI 1.80-5.16) and Norway HR = 2.87 (95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukemia had high risk of leukemia (HR = 2.39, 95% CI 1.61-3.55). CONCLUSION: Despite geographical distance and assumed large lifestyle differences, two genetically linked pediatric populations show similar incidences of CNS tumors and leukemia in the period 1966-2015. CNS tumors and leukemia aggregated in families in both countries.

Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: A cross-sectional study.

BACKGROUND AND AIMS: Diet may alter gene expression in immune cells involved in atherosclerotic cardiovascular disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. Therefore, we examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n = 130 women and 105 men). METHODS AND RESULTS: We used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. We detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated negatively with the Vegetarian DP. For women, the Vegetarian DP associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. A subsequent protein-protein interaction network analysis suggested that genes within these clusters might physically interact in biological networks. CONCLUSIONS: Although the present findings are exploratory, our analysis pipeline serves as a useful framework for studying the association between diet and gene expression.

Spinal cord injury and development of pressure injury during acute rehabilitation in Norway: a national retrospective cross-sectional study.

STUDY DESIGN: A national, retrospective, cross-sectional study. OBJECTIVES: To analyze the prevalence of pressure injury (PI), and characteristics associated with PI development in the hospitalized population of persons with a newly acquired spinal cord injury (SCI) between 2004 and 2014. SETTING: All three specialized Spinal Cord Units in Norway. METHODS: Demographic data related to prevalence and potential risk factors were retrieved from the electronic medical record (EMR). Statistical analyses were performed, using IBM SPSS Statistics, version 23. RESULTS: We identified 1012 individuals with a new SCI. Mean age at injury was 48 years (SD 19). The period prevalence of PI was 16% (95% CI = 0.14-0.19), and identified PI associations were complete SCI (OR = 0.1), being injured abroad (OR = 2.4), bowel (OR = 13), and bladder (OR = 9.2) dysfunction; comorbidities like diabetes mellitus 1 (OR = 7.9), diagnosed depression (OR = 3.8), ventilator support (OR = 3.0), drug abuse (OR = 3.0), and concurrent traumatic brain injury (OR = 1.7). Individuals in the age group of 15-29 years had higher odds of PI compared with middle-aged individuals (45-59 years). CONCLUSION: PI is a serious complication after SCI. The association between depression or comorbidity and PI occurrence should be investigated more thoroughly. We recommend implementation of a simple follow-up program regarding observation and prevention of PI. Increased awareness of factors that could contribute to PI will help to focus on better prevention and early recognition of PI. This will contribute to more optimal rehabilitation.

Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.

BACKGROUND: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults. METHODS: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30. RESULTS: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours. CONCLUSION: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

Meals with Similar Fat Content from Different Dairy Products Induce Different Postprandial Triglyceride Responses in Healthy Adults: A Randomized Controlled Cross-Over Trial.

BACKGROUND: Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. OBJECTIVE: We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. METHODS: A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th-75th percentile) age of 32 (25-46) y and body mass index of 23.6 (21.0-25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. RESULTS: Sour cream induced a 61% larger TG-iAUC0-6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0-6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0-6 h compared to cheese (P = 0.05). No differences in TG-iAUC0-6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0-6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0-6 h compared to butter (P = 0.006). No other meal effects were observed. CONCLUSIONS: High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. The study was registered at www.clinicaltrials.gov as NCT02836106.

Global test for high-dimensional mediation: Testing groups of potential mediators.

We address the problem of testing whether a possibly high-dimensional vector may act as a mediator between some exposure variable and the outcome of interest. We propose a global test for mediation, which combines a global test with the intersection-union principle. We discuss theoretical properties of our approach and conduct simulation studies that demonstrate that it performs equally well or better than its competitor. We also propose a multiple testing procedure, ScreenMin, that provides asymptotic control of either familywise error rate or false discovery rate when multiple groups of potential mediators are tested simultaneously. We apply our approach to data from a large Norwegian cohort study, where we look at the hypothesis that smoking increases the risk of lung cancer by modifying the level of DNA methylation.