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1.
  • Myte, Robin, et al. (författare)
  • Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
  • 2019
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:2, s. 327-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.
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2.
  • Chaparro, M. Pia, et al. (författare)
  • Childhood family structure and women's adult overweight risk : A longitudinal study
  • 2017
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45:5, s. 511-519
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aim of this study was to investigate whether women's adult overweight and obesity risk was associated with their childhood family structure, measured as their mothers' marital status history, during the women's first 18 years of life.METHODS: Using linked register data, we analyzed 30,584 primiparous women born in Sweden in 1975 who were between 19-35 years of age when their height and pre-pregnancy weight was recorded. The outcomes were women's overweight/obesity (body mass index (BMI) ≥ 25 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) and the predictor was mothers' marital status history, which was summarized using sequence analysis. We carried out nested logistic regression models adjusting for women's age and maternal sociodemographic characteristics.RESULTS: Mothers' marital status history was summarized into six clusters: stable marriage, stable cohabitation, married then divorcing, cohabiting then separating, varied transitions, and not with father. In fully adjusted models and compared with women whose mothers belonged to the stable marriage cluster: (1) women whose mothers belonged to the other marital status clusters had higher odds of overweight/obesity (odds ratio (OR) ranging 1.15-1.19; p < 0.05); and (2) women whose mothers belonged to the stable cohabitation (OR = 1.31; 95% confidence interval (CI) = 1.14-1.52), cohabiting then separating (OR = 1.23; 95% CI = 1.01-1.49), varied transitions (OR = 1.24; 95% CI = 1.11-1.39), and not with father (OR = 1.24; 95% CI = 1.00-1.54) clusters had higher odds of obesity.CONCLUSIONS: Women whose mothers were not in stable marriage relationships had higher odds of being overweight or obese in adulthood. The finding that even women raised in the context of stable cohabitation had higher odds of being overweight or obese is intriguing as these relationships are socially accepted in Sweden.
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4.
  • Chaparro, Pia, et al. (författare)
  • Regional inequalities in pre-pregnancy overweight and obesity in Sweden, 1992, 2000, and 2010
  • 2015
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:5, s. 534-539
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To investigate regional differences and time trends in women's overweight and obesity in Sweden. Methods: Using data from the Swedish Medical Birth Register (women aged 18 years, first pregnancy only) and the Total Population Register accessed through the Umea SIMSAM Lab, age-standardized prevalence of pre-pregnancy overweight/obesity (BMI 25 kg/m(2)) and obesity (BMI 30 kg/m(2)) were estimated by county for the years 1992, 2000, and 2010. Maps were created using ArcMap v10.2.2 to display regional variations over time and logistic regression analyses were used to assess if the observed trends were significant. Results: The prevalence of pre-pregnancy overweight/obesity and obesity increased significantly in all Swedish counties between 1992, and 2010. In 2010, Sodermanland and Gotland exhibited the highest age-standardized overweight/obesity (39.7%) and obesity (15.1%) prevalence, respectively. The sharpest increases between 1992 and 2010 were observed in Vasterbotten for overweight/obesity (75% increase) and in Gotland for obesity (233% increase). Across the years, Stockholm had the lowest prevalence of overweight/obesity (26.3% in 2010) and obesity (7.3% in 2010) and one of the least steep increases in prevalence of both between 1992 and 2010. Conclusions: Substantial regional differences in pre-pregnancy overweight and obesity prevalence are apparent in Sweden. Further research should elucidate the mechanisms causing these differences.
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5.
  • Claeson, Anna-Sara, 1974-, et al. (författare)
  • Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance
  • 2017
  • Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 121, s. 60-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60 min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24 h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI.
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6.
  • Feldman, Inna, et al. (författare)
  • Effectiveness and cost-effectiveness of the Salut Programme : a universal health promotion intervention for parents and children-protocol of a register-based retrospective observational study
  • 2016
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: There is inadequate evidence for the effectiveness and cost-effectiveness of health promotion interventions. The Salut Programme aims to reach all parents and children in the Vasterbotten County of Sweden with a combination of health promotion interventions initiated during pregnancy and continued over the childhood period. This study protocol describes an effectiveness study and an economic evaluation study, where the ongoing Salut Programme is compared to care-as-usual over the periods of pregnancy, delivery and the child's first 2 years of life. Methods: A register-based retrospective observational study design will be used with existing data sources with respect to exposures and outcomes. Outcomes of interest are clustered at 3 points: around the child's birth, 1 month after the child's birth and 2 years after the child's birth. We will simulate an experiment by retrospectively identifying and comparing children and their parents in the geographical areas where the Salut Programme was implemented since 2006 and onwards, and the areas where the Programme was not implemented before 2009. Outcomes will be analysed and compared for the premeasure period, and the postmeasure period for both groups. Our analysis combines difference-in-difference estimation with matching. A complementary analysis will be carried out on the longitudinal subsample of mothers who gave birth at least once during each of the time periods. The economic evaluation aims to capture the wider societal costs and benefits of the Salut Programme for the first 2 years of the children's lives. Incremental costs will be compared with incremental health gains and the results will be presented as a cost-consequence analysis. Ethics and dissemination: The Regional Ethical Review Board in Umea has given clearance for the Salut Programme research (2010-63-31M). No individual's identity will be revealed when presenting results. This study will provide information that can guide decision-makers to allocate resources optimally.
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7.
  • Gabrielsson, Linda, et al. (författare)
  • The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line
  • 2017
  • Ingår i: Pharmacology Research & Perspectives. - : John Wiley & Sons. - 2052-1707. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-c to induce COX-2. At the level of mRNA, COX-2 was induced > 1000-fold following 24 h of the treatment. Coincubation with PEA (10 mu mol/L) did not affect the levels of COX-2, but reduced the levels of prostaglandins D-2 and E-2 as well as 11- and 15-hydroxyeicosatetraenoic acid, which can also be synthesised by a COX-2 pathway in macrophages. These effects were retained when hydrolysis of PEA to palmitic acid was blocked. Linoleic acidderived oxylipin levels were not affected by PEA. No direct effects of PEA upon the oxygenation of either arachidonic acid or 2-arachidonoylglycerol by COX-2 were found. It is concluded that in lipopolysaccharide and interferon-c-stimulated RAW264.7 cells, PEA reduces the production of COX-2-derived oxylipins in a manner that is retained when its metabolism to palmitic acid is inhibited.
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8.
  • Gylling, Björn, 1978-, et al. (författare)
  • One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
  • 2019
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 947-956
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.
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9.
  • Häggström, Jenny, et al. (författare)
  • CovSel : An R Package for Covariate Selection When Estimating Average Causal Effects
  • 2015
  • Ingår i: Journal of Statistical Software. - : Foundation for Open Access Statistic. - 1548-7660. ; 68:1, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the R package CovSel, which reduces the dimension of the covariate vector for the purpose of estimating an average causal effect under the unconfoundedness assumption. Covariate selection algorithms developed in De Luna, Waernbaum, and Richardson (2011) are implemented using model-free backward elimination. We show how to use the package to select minimal sets of covariates. The package can be used with continuous and discrete covariates and the user can choose between marginal co-ordinate hypothesis tests and kernel-based smoothing as model-free dimension reduction techniques.
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11.
  • Häggström, Jenny, et al. (författare)
  • Is the Salut Programme an effective and cost-effective universal health promotion intervention for parents and their children? : a register-based retrospective observational study
  • 2017
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 7:9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This study investigates the effectiveness and cost-effectiveness of the Salut Programme, a universal health promotion intervention, compared with care-as-usual, over the periods of pregnancy, delivery and the child's first 2 years of life.METHOD: We adopted a register-based retrospective observational design using existing data sources with respect to both exposures and outcomes. Health outcomes and costs were compared between geographical areas that received care-as-usual (non-Salut area) and areas where the programme was implemented (Salut area). We included mothers and their children from both the Salut and non-Salut areas if: (1) the child was born 2002-2004 (premeasure period) or (2) the child was born 2006-2008 (postmeasure period). The effectiveness study adopted two strategies: (1) a matched difference-in-difference analysis using data from all participants and (2) a longitudinal analysis restricted to mothers who had given birth twice, that is, both in the premeasure and postmeasure periods. The economic evaluation was performed from a healthcare and a limited societal perspective. Outcomes were clustered during pregnancy, delivery and birth and the child's first 2 years.RESULTS: Difference-in-difference analyses did not yield any significant effect on the outcomes. Longitudinal analyses resulted in significant positive improvement in Apgar scores, reflecting the newborn's physical condition, with more children having a normal Apgar score (1 min +3%, 5 min +1%). The cost of the programme was international dollar (INT$)308/child. From both costing perspectives, the programme yielded higher effects and lower costs than care-as-usual, being thus cost-saving (probability of around 50%).CONCLUSIONS: Our findings suggest that the Salut Programme is an effective universal intervention to improve maternal and child health, and it may be good value for money; however, there is large uncertainty around the cost estimates.
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13.
  • Ju, Cheng, et al. (författare)
  • Collaborative-controlled LASSO for constructing propensity score-based estimators in high-dimensional data
  • 2019
  • Ingår i: Statistical Methods in Medical Research. - : Sage Publications. - 0962-2802 .- 1477-0334. ; 28:4, s. 1044-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • Propensity score-based estimators are increasingly used for causal inference in observational studies. However, model selection for propensity score estimation in high-dimensional data has received little attention. In these settings, propensity score models have traditionally been selected based on the goodness-of-fit for the treatment mechanism itself, without consideration of the causal parameter of interest. Collaborative minimum loss-based estimation is a novel methodology for causal inference that takes into account information on the causal parameter of interest when selecting a propensity score model. This “collaborative learning” considers variable associations with both treatment and outcome when selecting a propensity score model in order to minimize a bias-variance tradeoff in the estimated treatment effect. In this study, we introduce a novel approach for collaborative model selection when using the LASSO estimator for propensity score estimation in high-dimensional covariate settings. To demonstrate the importance of selecting the propensity score model collaboratively, we designed quasi-experiments based on a real electronic healthcare database, where only the potential outcomes were manually generated, and the treatment and baseline covariates remained unchanged. Results showed that the collaborative minimum loss-based estimation algorithm outperformed other competing estimators for both point estimation and confidence interval coverage. In addition, the propensity score model selected by collaborative minimum loss-based estimation could be applied to other propensity score-based estimators, which also resulted in substantive improvement for both point estimation and confidence interval coverage. We illustrate the discussed concepts through an empirical example comparing the effects of non-selective nonsteroidal anti-inflammatory drugs with selective COX-2 inhibitors on gastrointestinal complications in a population of Medicare beneficiaries.
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14.
  • Myte, Robin, et al. (författare)
  • Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk
  • 2016
  • Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 27:6, s. 787-796
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83.
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15.
  • Myte, Robin, 1989- (författare)
  • Metabolic Risk Factors and Molecular Subtypes of Colorectal Cancer
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Colorectal cancer (CRC) is a heterogeneous disease developing from distinct pathways, resulting in tumor subtypes with large differences in clinical and molecular characteristics. Molecular characteristics are increasingly being used clinically to guide therapy. However, whether molecular subtypes of CRC differ in etiology or risk factors is not clear. Clarifying such potential differences may lead to an improved understanding of CRC etiology, with implications for CRC prevention and screening.Aim: The aim of this thesis was to investigate whether risk factors related to energy metabolism, such as body fatness, and one-carbon metabolism, such as circulating B-vitamin status, were associated with specific subtypes of CRC defined by molecular characteristics of the tumor. Methods: These prospective studies are based on data and blood samples from cohorts within the population-based Northern Sweden Health and Disease Study (NSHDS). Prospective CRC cases with available archived tumor tissue were analyzed for key molecular features (KRAS and BRAF mutation status, Microsatellite instability (MSI) status, and CpG Island Methylator Phenotype (CIMP) status). Paper I was a cohort study of metabolic factors related to the metabolic syndrome (117 687 participants). Paper II was a nested-case control study on circulating insulin resistance-markers and adipokines (1010 cases and 1010 matched controls). Papers III and IV were nested case-control studies of one-carbon metabolism biomarkers and genetic variants (613 cases and 1190 matched controls).Results: In paper I, we observed associations between metabolic factors, such as BMI, blood pressure, and blood lipids, and CRC risk consistent with previous studies. These associations were similar regardless of tumor KRAS and BRAF mutation status. In paper II, circulating biomarkers of insulin resistance and adipokines were not associated with the risk of CRC or specific molecular subtypes of CRC defined by KRAS and BRAF mutation or MSI status. In paper III, higher circulating levels of metabolites involved in the methionine cycle (namely, betaine and methionine) were associated with a lower CRC risk. In paper IV, we found no support for clear subtype-specific roles of any circulating one-carbon metabolism biomarker or genetic variants in CRC development.Conclusions: The result of these prospective studies suggests that metabolic factors related to energy metabolism and one-carbon metabolism are generally associated with the risk of CRC, regardless of major subtypes defined by key molecular tumor features. If causal, metabolic risk factors likely influence the risk of colorectal cancer through more than one carcinogenic pathway.
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16.
  • Myte, Robin, et al. (författare)
  • One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status
  • 2018
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.
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17.
  • Myte, Robin, et al. (författare)
  • Untangling the role of one-carbon metabolism in colorectal cancer risk : a comprehensive Bayesian network analysis
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease.
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18.
  • Persson, Emma, 1981-, et al. (författare)
  • Data-driven algorithms for dimension reduction in causal inference
  • 2017
  • Ingår i: Computational Statistics & Data Analysis. - : Elsevier BV. - 0167-9473 .- 1872-7352. ; 105, s. 280-292
  • Tidskriftsartikel (refereegranskat)abstract
    • In observational studies, the causal effect of a treatment may be confounded with variables that are related to both the treatment and the outcome of interest. In order to identify a causal effect, such studies often rely on the unconfoundedness assumption, i.e., that all confounding variables are observed. The choice of covariates to control for, which is primarily based on subject matter knowledge, may result in a large covariate vector in the attempt to ensure that unconfoundedness holds. However, including redundant covariates can affect bias and efficiency of nonparametric causal effect estimators, e.g., due to the curse of dimensionality. In this paper, data-driven algo- rithms for the selection of sufficient covariate subsets are investigated. Under the assumption of unconfoundedness we search for minimal subsets of the covariate vector. Based on the framework of sufficient dimension reduction or kernel smoothing, the algorithms perform a backward elim- ination procedure testing the significance of each covariate. Their performance is evaluated in simulations and an application using data from the Swedish Childhood Diabetes Register is also presented.
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19.
  • Pulkki-Brännström, Anni-Maria, et al. (författare)
  • The equity impact of a universal child health promotion programme
  • 2019
  • Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 29:Suppl 4, s. 103-103
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: We aimed to evaluate whether the Salut Programme, a universal child health promotion intervention, aimed to strengthen healthy lifestyles in northern Sweden, had any effect on income-related inequalities in positive birth outcomes for children and on healthcare use for children and their mothers.Methods: Mother’s residence and child’s date of birth determined whether the child and the mother belonged to the control group (areas that received care-as-usual) or the intervention group (areas with the intervention implemented from 2005), during the pre-measure period (children born 2002-2004) and the post-measure period (children born 2006-2008). The sum of parents’ taxable income was used for socioeconomic ranking. We computed the standard concentration index for six binary indicators of positive birth outcomes, and for inpatient and day patient care for children and mothers during the two years after delivery. Using a difference-in-difference approach, we assessed whether the extent of inequality changed over time between areas.Results: Income-related inequalities in child health status at birth and in child healthcare use were absent, except that full-term pregnancies were concentrated among the poor at pre-measure in the intervention group. However, mothers’ healthcare use was significantly pro-poor in the control group. The extent of inequality changed between pre- and post-measure periods for two outcomes: the pro-poor concentration of full-term pregnancies in the intervention group at pre-measure disappeared at post-measure; and an increase in pro-poor concentration of normal birth weight in the control group was not matched by a similar increase in the intervention group. Inequalities in healthcare use did not change significantly.Conclusions: Birth outcomes and child healthcare use seemed to be equitably distributed. However, the results raise concerns whether the intervention may have reduced the pro-poor concentration of positive birth outcomes.Key messagesThere are concerns that participation in universal health promotion programmes differs by socioeconomic status, although few public health interventions have been evaluated from an equity perspective.Birth outcomes and child healthcare use in Northern Sweden seemed to be equitably distributed across different socioeconomic groups.
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20.
  • Tidholm, Anna, et al. (författare)
  • Congenital heart defects in cats: a retrospective study of 162 cats (1996-2013)
  • 2015
  • Ingår i: Journal of Veterinary Cardiology. - : Elsevier BV. - 1760-2734 .- 1875-0834. ; 17, s. S215-S219
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study the prevalence and distribution of congenital heart defects in cats presented at two referral centers in Sweden between 1996 and 2013.Animals: 162 client-owned cats with congenital heart defects.Methods: Case records of cats diagnosed with congenital heart disease were reviewed retrospectively.Results: The overall prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. A total of 182 heart defects were identified as 16 cats were diagnosed with more than one defect. Ventricular septal defect (VSD) was most prevalent, found in 50% of cats, followed by tricuspid valve dysplasia (11%), pulmonic stenosis (10%), atrial septal defect (10%), aortic stenosis (9%), mitral valve dysplasia (9%), tetralogy of Faltot (5%), patent ductus arteriosus (3%), common atrioventricular canal (2%), and the following defects that each accounted for 0.6% of cats: double chamber right ventricle, double outlet right ventricle, endocardial fibroelastosis, dextroposition of the aorta, persistent right aortic arch, and pulmonary atresia.Conclusion: The prevalence of congenital heart disease was 0.2% of the total number of patient cats, and 8% of cats diagnosed with heart disease. Ventricular septal defect was the most common congenital heart defect in this study. (C) 2014 Elsevier B.V. All rights reserved.
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21.
  • Wallin, Gabriel, 1991- (författare)
  • Extensions of the kernel method of test score equating
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis makes contributions within the area of test score equating and specifically kernel equating. The first paper of this thesis studies the estimation of the test score distributions needed in kernel equating. There are currently two families of models implemented within kernel equating for this purpose, namely log-linear models and item response theory models. The impact of model selection criteria for these models on the equated scores are studied using both empirical and simulated data.The second paper focuses on the continuization of the estimated score distributions, where different bandwidth selection methods are studied. The study considers multiple data collection designs, sample sizes and score distributions and investigates how large impact the bandwidth selection has on the equated scores.When the test groups differ in their ability distributions it is necessary to adjust for such differences to make fair comparisons possible. The most common way of adjusting for ability imbalance is by using items that are common for both test forms, known as anchor items. If no such items are available, it has been suggested to use background information about the test-takers instead. However, when the covariate vector of background information increases, the combination of covariates with no observations tends to increase as well. The third paper of this thesis therefore suggests to transform the covariate vector into a scalar propensity score. Two equating estimators are suggested under this setting and the standard error of equating (SEE) for both estimators are given.The SEE for kernel equating has previously been derived using the delta method. The fourth paper revisits the Bahadur representation of sample quantiles to derive the SEE. Both methods of calculating the SEE are compared, and it is shown that they are equivalent for all common data collection designs when the terms of the Bahadur SEE are estimated using Taylor expansions. An implementation of an alternative estimator of the Bahadur SEE for which the equivalence result does not hold is also included to illustrate when the two methods differ.
  •  
22.
  • Wallin, Gabriel, et al. (författare)
  • How to select the bandwidth in kernel equating : an evaluation of five different methods
  • 2018
  • Ingår i: Quantitative psychology. - Cham, Switzerland : Springer. - 9783319772486 - 9783319772493 ; , s. 91-100
  • Bokkapitel (refereegranskat)abstract
    • When using kernel equating to equate two test forms, a bandwidth needs to be selected. The bandwidth parameter determines the smoothness of the continuized score distributions and has been shown to have a large effect on the kernel density estimate. There are a number of suggested criteria for selecting the bandwidth, and currently four of them have been implemented in kernel equating. In this paper, all four of the existing bandwidth selectors suggested for kernel equating are evaluated and compared against each other using real test data together with a new criterion that implements leave-one-out cross-validation. Although the bandwidth methods generally were similar in terms of equated scores, there were potentially important differences in the upper part of the score scale where critical admission decisions are typically made.
  •  
23.
  • Watts, Eleanor L., et al. (författare)
  • The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies
  • 2019
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:12, s. 3244-3256
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
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