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The issue of violence against women in Sweden was long considered to be a private matter. Until the eighties, violence against women was not seen as a societal problem. Once the non-interventionist attitude towards violence against women was abandoned, other tensions followed. This chapter explores some of these tensions as they have played out in the context of support to battered women, with a view to discussing them in relation to the Istanbul Convention’s Article 23, which obliges State Parties to provide for easily accessible shelters. The main tensions surrounding the issue of violence against women in Sweden have concerned the conceptualisation of violence against women and the different ways of organising society’s response to such violence. In this chapter, we explore these tensions by revisiting the development of the Swedish women’s shelter movement and by examining legislative material, in particular major reforms on victim support. The Istanbul Convention places violence against women in the context of gender inequality. It requires that a contracting State take interest in and actively work against violence against women and acknowledge this violence as a problem, which public authorities are responsible to combat. The Swedish case illustrates that increased public responsibility may sometimes entail dilemmas for feminist goals and perspectives.

Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care. Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual. Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated. Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations. Funding Agencies|Kamprad Foundation [20170102]; Heart- and Lung FoundationSwedish Heart-Lung Foundation [20170251]; Swedish Research CouncilSwedish Research Council [2018-02648]; Gothenburg Centre for Person-Centred Care (GPCC)

Additional file 1: Table S1. Formulas used to estimate relative GFR (mL/min/1.73 m2) by The Chronic Kidney Disease Epidemiology Collaboration. Table S2. Formulas used to estimate relative GFR (mL/min/1.73 m2) by our laboratory. Table S3. Spearman rank correlations (p-value) between serum concentrations of PFAS and kidney function parameters in early pregnancy. Table S4. Spearman rank correlations (p-value) between serum concentrations of PFAS and kidney function parameters in late pregnancy. Table S5. Unadjusted Spearman rank correlations (p-value) between pregnancy-induced changes in serum concentrations of PFAS and parallel changes in kidney function parameters.

To determine how maternal obesity or gestational diabetes mellitus (GDM) affect infant body size and body composition during the first year of life. Eighty three normal-weight (NW) women, 26 obese (OB) women, and 26 women with GDM were recruited during pregnancy. Infant body composition was determined by air-displacement plethysmography at 1 and 12 weeks, and anthropometric measurements made until 1 year of age. Girl infants born to OB women and women with GDM had a higher body-fat percentage (BF%) at 1 and 12 weeks of age than girls born to NW women. Girls had higher BF% than boys in OB and GDM groups only. Maternal HbA1c and fasting plasma glucose correlated with girl infant BF% at 1 week of age. Maternal weight at start of pregnancy correlated with birthweight in NW and OB groups, but not the GDM group. OB group infants showed greater BMI increases from 1 week to 1 year than both NW and GDM group infants. Results show that both maternal glycaemia and obesity are determinants of increased early life adiposity, especially in girls, with glycaemic levels being more influential than maternal weight for infants born to women with GDM.

Background: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. Methods: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. Results: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P P P =0.028). Prior stroke/systemic embolism (HR, 2.58; P >0.001) followed by troponin T (HR, 1.45; P Conclusions: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients’ risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p(54–63)=1.50×10(−9), OR(54–63)=1.28, 95%CI(54–63)=1.18–1.39; p(64+)=2.14×10(−11), OR(64+)=1.32, 95%CI(64+)=1.21–1.43] and rs11979158 [p(54–63)=6.13×10(−8), OR(54–63)=1.35, 95%CI(54–63)=1.21–1.50; p(64+)=2.18×10(−10), OR(64+)=1.42, 95%CI(64+)=1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p(18–53)=9.30×10(−11), OR(18–53)=1.76, 95%CI(18–53)=1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’-like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p=0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’

Background There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. Objectives The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. Methods Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. Results Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients’ age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p 2 DS 2 -VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p 2 DS 2 -VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. Conclusions In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)

Current developments in the Swedish news business have resulted in clashes between the professional stands of journalists and the incentives of their managers, or—from a theoretical perspective—a c...

Purpose: This study investigated how postexercise intake of placebo (PLA), protein (PRO), or carbohydrate (CHO) affected fat oxidation (FO) and metabolic parameters during recovery and subsequent exercise. Methods: In a cross-over design, 12 moderately trained women (VO2max 45 ± 6 ml·min−1·kg−1) performed three days of testing. A 23-min control (CON) incremental FO bike test (30–80% VO2max) was followed by 60 min exercise at 75% VO2max. Immediately postexercise, subjects ingested PLA, 20 g PRO, or 40 g CHO followed by a second FO bike test 2 h later. Results: Maximal fat oxidation (MFO) and the intensity at which MFO occurs (Fatmax) increased at the second FO test compared to the first following all three postexercise drinks (MFO for CON = 0.28 ± 0.08, PLA = 0.57 ± 0.13, PRO = 0.52 ± 0.08, CHO = 0.44 ± 0.12 g fat·min−1; Fatmax for CON = 41 ± 7, PLA = 54 ± 4, PRO = 55 ± 6, CHO = 50 ± 8 %VO2max, p max were not significantly different between PLA and PRO, but lower for CHO. PRO and CHO increased insulin levels at 1 h postexercise, though both glucose and insulin were equal with PLA at 2 h postexercise. Increased postexercise ketone levels only occurred with PLA. Conclusion: Protein supplementation immediately postexercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 h later. Neither did it affect resting fat oxidation during the postexercise period despite increased insulin levels and attenuated ketosis. Carbohydrate intake dampened the increase in fat oxidation during the second test, though a significant increase was still observed compared to the first test.

To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1,1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3,1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.GDF-15 concentrations were1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P.0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P.0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.

Background Cardiac biomarkers and left ventricular hypertrophy ( LVH ) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes. Methods and Results Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE ‐ LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT ‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG . Cox models were adjusted for baseline characteristics, LVH , and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly ( P NT ‐pro BNP , 1.32 (1.25–1.38); hs cardiac troponin I, 1.67 (1.57–1.78); hs troponin T, 1.38 (1.32–1.44); and growth differentiation factor‐15, 1.09 (1.05–1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT ‐pro BNP, 1.09 (1.00–1.19); hs cardiac troponin I, 1.09 (1.03–1.15); hs troponin T, 1.14 (1.06–1.24); and growth differentiation factor‐15, 1.22 (1.08–1.38) (all P NT ‐pro BNP , 1.24 (1.17–1.31); hs cardiac troponin I, 1.13 (1.10–1.17); hs troponin T, 1.28 (1.23–1.34); and growth differentiation factor‐15, 1.31 (1.22–1.42) (all P LVH was not significantly associated with stroke or death after adjustment for biomarkers. Conclusions Cardiac biomarkers are significantly associated with LVH . The prognostic value of biomarkers for stroke and death is not affected by LVH . The prognostic information of LVH is attenuated in the presence of cardiac biomarkers. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00262600.

Purpose: Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown. Methods: rLTL was measured by qPCR in a Swedish population-based glioma case–control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification. Results: Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02–1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q co-deletion, or EGFR amplification, after adjusting for age at diagnosis and sex. Conclusions: In this Swedish glioma case–control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk.

Journalistic work and organizations are currently undergoing rapid change. One of the most striking features of this transformation seems to be an increasing influence of managerial discourse in the newsroom. Editorial leadership is proving to be more professionalized, standardized and accentuated than before, which could affect journalistic autonomy and status. In this article we investigate the shifting power balance in news production by focusing on the management–staff relationship in Swedish newspapers and discussing the possible consequences of this development for the professional autonomy and status of journalists. Empirical support is drawn from two national surveys of Swedish journalists and a small interview study of Swedish newspaper journalists, and the data is analysed within a framework of professional and organizational theory. The results indicate a move towards managerial dominance in the newsroom during the last decade, but also that journalists to some extent seem to approve of this development. Even so, the results may be another indication of a de-professionalization of journalists to the benefit of the managerial group in the news business. The article aims at contributing to a further understanding of the changing organizational behaviour of news companies and how journalism practices in the newsroom are being challenged by an excessive growth of managerialism, which not only inhibit and limit journalistic professionalism, but also leads to a loss of democracy.

Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (gamma-tocopherol, alpha-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of alpha-tocopherol (p=0.0018) and gamma-tocopherol (p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of alpha- and gamma-tocopherol levels: 1.2 for alpha-T (p=0.018) and 1.6 for gamma-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (alpha-T, 95% CI: 1.0-3.0) and 2.1 (gamma-T, 95% CI: 1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.

Objective During pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated. Methods Women were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis. Results Immunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW. Conclusions High serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.

During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B,PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations. Electronic supplementary material The online version of this article (doi:10.1007/s11060-016-2066-4) contains supplementary material, which is available to authorized users.

Objective Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Methods The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Results The IL-6 median level was 2.3 ng/L (IQR 1.5–3.9), median CRP level was 2.2 mg/L (1.0–4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Conclusions In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding. Trial registration number ClinicalTrials.gov identifier: NCT00412984 post-results.

In the judicial context, the law of rape is plied chiefly around two central concepts: force and non-consent. These concepts are analogues to male and female sexuality and lie at the heart of what may be described as the dichotomy of rape law. When force is part of the legislative definition of rape, non-consent seems to be used in case law as an instrument to decide whether force may be proven. On the contrary, when the legislative definition contains non-consent, force is generally looked at in order to prove non-consent.

Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6 years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR = 1.34, P

Background: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA. Methods: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation. Results: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09–1.35; P = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P Conclusions: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts. Impact: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.

BACKGROUND: Germline variants associated with predisposition for cancer are frequently located in genes involved in genome integrity. The telomeres at the chromosome ends are important in maintaining genomic stability, and germline variants in telomere regulating genes have been associated with both telomere length and glioma risk in repeated studies. In this case-control study, we investigated the association of measured leukocyte telomere length with genetically estimated telomere length risk score (TL-GRS) and the 27 currently identified glioma risk loci. MATERIAL AND METHODS: Peripheral blood samples from 421 glioma patients and 671 age- and gender- matched controls were analyzed for relative leukocyte telomere length (rLTL) by qPCR. Genetic variants in telomere and glioma associated genes were genotyped by SNP-arrays, and TL-GRS was calculated. Associations between the genotypes of interest and rLTL were characterized by means of “multinomial logistic regression analysis” including covariates. RESULTS: Glioma patients had similar TL-GRS, but longer rLTL, than controls. Long rLTL was a risk factor for glioma in contrast to TL-GRS that was not. Among controls, a correlation between rLTL and TL-GRS was found, but this association was not seen among glioma cases. Notably, the correlation between rLTL and TL-GRS was stronger among men than women. CONCLUSION: In this Swedish glioma case/control cohort, long rLTL was associated with increased risk of glioma but high TL-GRS was not. The association between rLTL and TL-GRS seen in controls was absent in glioma cases.

Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P0.001), NT-proBNP with heart failure death (HR, 1.62; P0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P0.001) followed by troponin T (HR, 1.45; P0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

For decades, the media have frequently been instrumental in framing rape cases by linking the deed with the place. This study demonstrates that law courts are not innocent of such social framing; on the contrary, they are significant agents. We argue that courts, by shaping the plot in rape cases, participate in an ongoing cultural production of meaning, although in a more subtle and ambivalent way than the media. In a narrative analysis of three contemporary rape cases in Sweden, we bring together feminist research on place with the concepts of vulnerability and agency. We argue that place is framed as ambivalent in relation to vulnerability and agency and dependent on the positioning of the plaintiff and the defendant. In court narratives geographical places are made relevant, including the locations where the alleged rapes took place. Court narratives of rape include highly ambivalent connotations to place in relation to vulnerability and agency, distinguished by different narratives and outcomes in the various instances. The legal and social implications of our work should include an awareness of the relevance of place in relation to rape. (Less)

Background Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF. Objectives To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial. Methods HAS-BLED, ORBIT, ATRIA and HEMORR2HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated. Results There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P

This article analyses whether reading patterns differ between readers of a printed newspaper and readers of an online newspaper. Such a question is hardly new but has increased in importance as more readers switch from printed to digital news media. The analysis compares data collected from a readership study focused on the printed local Swedish newspaper VLT (Vestmanland Lans Tidning) and data collected by automatic registration of the number of unique page views on the news site vlt.se. Both data collections were made during the same two-week period in September 2013. The results show some obvious differences as online readers focus on the first page of the online edition, while print readers focus on the editorial sections inside the newspaper. Print readers also display a more diverse reading repertoire, while online readers concentrate on a limited number of subjects. However, when the time factor is taken into consideration—the amount of time spent on each article—the reading patterns of print reade...

Since the 1990s, Western society and its media have veered towards increased market orientation. In this process, values of individualisation and self-interest have emerged as important patterns. Research has shown that media professionals have become slightly more commercially oriented over time, although public interest remains the most important factor when the duties of journalism are fulfilled. What can be said, however, about the journalists of the future? This study aims at analysing why students from different generations are attracted by journalism as profession. It is done by drawing empirical support from two questionnaires completed by first-year students in Sweden in 1994 and 2012. The analysis deals with approximately 160 journalism students and takes as its point of departure the theoretical framework of commercialisation and generational belonging. The main result shows that journalism students have moved slightly towards an increased market orientation but similarly also towards an increa...

Background: Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case–control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. Methods: To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. Results: We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. Cancer Epidemiol Biomarkers Prev; 24(5); 810–6. ©2015 AACR.

BACKGROUND Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. METHODS Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. RESULTS Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the concentrations of both troponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a median 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31–2.27)], cardiac death [3.14 (2.35–4.20)], and myocardial infarction [2.99 (1.78–5.03)] than those with both troponins below median (all P < 0.005). Intermediate risks were observed when only 1 troponin was above the median. When combined with clinical information, each marker provided similar prognostication and had comparable c-index. CONCLUSIONS cTnI and cTnT concentrations are moderately correlated and measurable in plasma of most AF patients. The risk of stroke and cardiovascular events is highest when both troponins are above median concentrations. Each troponin provides comparable prognostic information when combined with clinical risk factors. ClinicalTrials.gov/NCT00412984

Large quantities of water are required to produce the food for a nation, some of which is derived within the country and some associated with imported food commodities. In this study, we consider the spatially explicit potential impact of alternative healthier eating scenarios for the UK on global blue water scarcity using the concept of a water scarcity footprint. The water required to produce the food consumed by the UK was estimated at 52.6 Gm 3 /y of which 93% is from rainfall at the point where it falls and 7% is “blue” water withdrawn from surface and ground water resources. Five alternative healthier diets were considered and the impact on the blue water scarcity footprint was modest (ranging from −3% to +2% compared to baseline). However more significant impacts were projected on the geographical distribution of the blue water scarcity footprint. This study has shown that if current trade patterns continue, policies to promote healthier eating in the UK may contribute to increased blue water scarcity at home and in other parts of the world. The use of virtual water estimates and global datasets of water scarcity can help to understand the potential environmental impacts of alternative diets.

BackgroundGenome-wide association studies (GWAS) have identified 25 risk variants for glioma, which explain ~30% of heritable risk. Most glioma histologies occur with significantly higher incidence in males. A sex-stratified analysis ide7ntified sex-specific glioma risk variants, and further analyses using gene- and pathway-based approaches may further elucidate risk variation by sex.MethodsResults from the Glioma International Case-Control Study were used as a testing set, and results from three GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for autosomal SNPs found to be nominally significant (p−6in ⅔ algorithms.Results25 genes within five regions and 19 genes within six regions reached the set significance threshold in at least 2/3 algorithms in males and females, respectively.EGFRandRTEL1-TNFRSF6Bwere significantly associated with all glioma and glioblastoma in males only, and a female-specific association inTERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the Telomeres, Telomerase, Cellular Aging, and Immortality pathway in both males and females.ConclusionsThese results suggest that there may be biologically relevant significant differences by sex in genetic risk for glioma. Additional gene- and pathway-based analyses may further elucidate the biological processes through which this risk is conferred.

OBJECTIVE: To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to postpregnancy in relation to weight changes, fat mass and glucose metabolism. CONTEXT: With high postpartum weight retention being a risk factor in future pregnancies and of lifelong obesity, we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable. DESIGN: Women were followed for 5 ± 1 years after pregnancy and divided into two groups, weight stable and weight gain, by weight change from start of pregnancy. PATIENTS: Twenty‐five women (BMI 27 ± 5 kg/m2) recruited at admission for elective caesarean section. MEASUREMENTS: CSF and serum levels of agouti‐related protein (AgRP), leptin and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA‐IR). RESULTS: S‐AgRP levels during pregnancy were lower in the weight stable group and a 1 unit increase in s‐AgRP was associated with 24% higher odds of pertaining to the weight gain group. After pregnancy, s‐AgRP increased in the weight stable group but decreased in the weight gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their prepregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA‐IR. CONCLUSION: S‐AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long‐term regulation of body weight.

Background Renal function may decline over time, and the efficacy and safety of dabigatran in atrial fibrillation (AF) in relation to renal function changes are unknown. Methods The RE-LY trial randomized 18,113 patients with AF to 2 doses of dabigatran or warfarin for stroke prevention. Serial creatinine measurements were available in 16,988 patients. The relations between treatment, outcomes, and renal function (Cockcroft-Gault) were investigated using Cox-regression (1) with renal function as a time-dependent covariate and (2) according to worsening renal function (WRF) during follow-up, predefined as a decline in estimated glomerular filtration rate >20% from baseline. Results During a median follow-up of 1.8 years, 4,106 (24.2%) participants were observed to have WRF, and 12,882 (75.8%) had stable renal function. The risks of all-cause mortality and major bleeding were higher in patients with WRF versus those with stable renal function (hazard ratio [95% CI]: 2.17 [1.81-2.59] and 1.43 [1.19-1.71], respectively; both P 80 mL/min) during follow-up (interaction P = .026). Conclusions In AF, WRF was associated with a higher risk of death and major bleeding. The efficacy and safety profile of dabigatran compared with warfarin was similar irrespective of renal function changes over time. Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function during follow-up.

Context Gestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM. Objective To find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum. Design The metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 ± 0.6) and postpartum (10.5 ± 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period. Results Women with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women. Conclusions Postpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.

Background Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker–based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short‐term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short‐term risk estimate. Methods and Results According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N‐terminal pro‐B‐type natriuretic peptide were measured with high‐sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small (median change cardiac troponin T +2.8%, troponin I +2.0%, and N‐terminal pro‐B‐type natriuretic peptide +13.5%) and within‐subject correlation was high (all ≥0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person‐years of follow‐up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65–0.76) as compared with 0.70 (95% CI, 0.65–0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes. Conclusions In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker‐based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00412984.

Background: In glioma, a malignant brain tumour with poor prognosis, the etiology is largely unkown. Rare inherited syndromes, and high doses of ionising radiation are associated with increased risk of glioma. Common genetic variants have been associated with risk of glioma, and familial glioma have been associated with genetic variants in genes functionally important in telomere regulation (e.g. RTEL, TERT and POT1). The association between telomere length and risk of cancer is complex and seems to be tumour type dependent. Patients with asthma have significantly shorter telomeres than those of control subjects, and a protective effect has been observed with an inverse association with allergies and asthma and glioma risk. Methods: We investigated population based glioma case-control series (431 cases and 672 controls) from Sweden at diagnosis with a quantitative PCR method for relative leukocyte telomere length measured in blood confirming with direct measurement of the association between telomere length and risk of glioma. We also explored the relationship between, age, gender, allergies and asthma, as these are established factors associated both with telomere length and glioma. Results: Longer relative leukocyte telomere length was significantly associated with increased risk of glioma, adjusting for age and gender (OR=2.23, CI: 1.11–4.47). As expected, for patients with allergies there was a protective effect with an inverse association with glioma risk, adjusting for age and gender (OR=0.64, CI; 0.48–0.85). Nevertheless, when analysing specific types of allergy, eczema (OR=0.66, CI; 0.41–1.08) and water eyes (OR=0.52, CI; 0.31–0.88) appeared to be more protective against glioma, compared to asthma (OR=0.92, CI; 0.59–1.41), and respiratory symptoms (OR=1.14, CI; 0.71–1.84) which showed no protective effect against glioma. Additionally adjusting for allergies did not markedly change the OR between relative leukocyte telomere length and glioma risk, indicating that the protective effect having allergies seems not to be coupled to telomere length. Conclusions: The adverse association of longer telomere and risk of glioma displays the complexity in understanding the biological role of telomere length and risk of developing cancer.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

Background D-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. Objectives To evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. Methods In the ARISTOTLE trial, 18 201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14 878 patients at randomization. The cohort was separated into two groups; not receiving vitamin K antagonist (VKA) treatment and receiving VKA treatment at randomization. Results Higher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR] [Q4 vs. Q1] 1.72, 95% confidence interval [CI] 1.14–2.59, P = 0.003), death (HR [Q4 vs. Q1] 4.04, 95% CI 3.06–5.33) and major bleeding (HR [Q4 vs. Q1] 2.47, 95% CI 1.77–3.45, P

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Background— Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function. Methods and Results— Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C–based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to P >0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively ( P Conclusions— The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00262600.

Background— High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. Methods and Results— At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (≥1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels ≥23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42–2.78), P =0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05–6.70), P P =0.0250. Adding hs-TnI levels to the CHA 2 DS 2 VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. Conclusions— Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA 2 DS 2 VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

The development of news production over the last decade has accentuated the negotiation between two forces of change: professional discourse and managerial discourse. The first characterizes journalistic identity by normative ideals and serves to legitimize journalists as an autonomous and self-regulating group. Managerial discourse, on the other hand, expresses the globalization of values and economy in the labour market, as well as in the area of communication, streamlining organizational models, and suggesting a business thinking common to several industries, in addition to an evolving view of the individual as an entrepreneur. Managerialism has implications for all levels of news work and, above all, emphasizes audience orientation, as the will of the audience becomes imperative. It promotes a form of leadership rather new to Scandinavian news organizations by strongly bringing the key values of profit and efficiency to the negotiating table. This article focuses on the constant negotiation between di...

OBJECTIVE:This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for ...

MISER chromatography was evaluated to increase data processing speed for a rapid, miniaturized in vitro formulation screen. This approach permitted quick data interpretation by eliminating time-consuming steps such as integration, quantitation and report generation. Some flexibility in analytical methodology was lost due to limited instrument platforms capable of injecting multiple samples and acquiring all data in a single chromatogram. In our instrumental setup, an isocratic run was used to perform MISER chromatography, producing results comparable to our generic gradient methods while reducing processing times. This novel data format was easily interpreted and provides equivalent information to a formulation scientist as compared to traditional tabulated reports.

The functional importance of glycolipids has emphasized the need for more sensitive methods of detection, characterization, and quantification than has often been possible using traditional thin-layer chromatographic techniques. We describe the use of ceramide glycanase and HPLC to identify and quantify gangliosides in which the carbohydrate is in Glcbeta1--> linkage with ceramide. Detection of released carbohydrate was by fluorescent labeling with 2-aminobenzamide at the reducing terminal prior to HPLC analysis. Under the conditions described, ceramide glycanase hydrolyzed all of the common gangliosides studied, offering a broad spectrum of specificity. Release and detection of carbohydrate were linear over a wide range (over two orders of magnitude) of micromolar glycolipid substrate concentrations. Use of an N-linked glycan as an internal standard allowed accurate quantification and a recovery of 93% was achieved. The method additionally maintained the sensitivity (chromatographic peaks containing 1 pmol were readily detected from tissue samples) and comparable resolution to related assays. This was shown by the separation, not only of isomeric carbohydrates from the "a" and "b" series, but also of ganglioside carbohydrate differing only by the presence of either N-acetyl- or N-glycolylneuraminic acid. Application of the method to neutral glycosphingolipids and to tissue samples, including 10-microl quantities of plasma, is illustrated. Glycan structures were confirmed by exoglycosidase digestion and/or matrix-assisted laser desorption/ionization mass spectrometry.

N-Butyldeoxynojirimycin (NB-DNJ) inhibits the ceramide glucosyltransferase which catalyses the first step in glycosphingolipid (GSL) biosynthesis. It has the potential to be used for the treatment of the GSL lysosomal storage diseases and is currently in clinical trials for the treatment of type 1 Gaucher's disease. However, NB-DNJ is also a potent inhibitor of other enzymes, including alpha-glucosidase I and II, which could potentially cause side effects in patients receiving life-long therapy. Wetherefore evaluated a potentially more selective GSL biosynthesis inhibitor, N-butyldeoxygalactonojirimycin (NB-DGJ), in vitro and in vivo. The distribution and degree of GSL depletion in the liver of mice treated with NB-DGJ or NB-DNJ were equivalent. Mice treated with NB-DGJ had normal body weights and lymphoid organ sizes, whereas NB-DNJ-treated mice showed weight loss and partial lymphoid organ shrinkage. NB-DNJ inhibited glycogen catabolism in the liver, whereas NB-DGJ did not. NB-DNJ was also a potent inhibitor of sucrase and maltase in vitro but not of lactase, while NB-DGJ inhibited lactase but not sucrase or maltase. NB-DGJ is therefore more selective than NB-DNJ, and deserves to be evaluated for human therapy.