SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Malin S) srt2:(2010-2014)"

Sökning: WFRF:(Malin S) > (2010-2014)

  • Resultat 1-50 av 79
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 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.
  •  
2.
  • Grote, V. A., et al. (författare)
  • Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk : a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2011
  • Ingår i: Diabetologia. - New York : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 54:12, s. 3037-3046
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.Methods: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [>= 6.5%, 48 mmol/mol] vs lowest [<= 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.Conclusions/interpretation: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.
  •  
3.
  • Grote, V. A., et al. (författare)
  • Inflammation marker and risk of pancreatic cancer: A nested case-control study within the EPIC cohort
  • 2012
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106, s. 1866-1874
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. Results: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. Conclusion: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer. © 2012 Cancer Research UK.
  •  
4.
  • Rohrmann, S., et al. (författare)
  • Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition
  • 2012
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106, s. 1004-1010
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.Methods:Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables.Results:Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (O=R1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction0.154). Conclusion: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk. © 2012 Cancer Research UK All rights reserved.
  •  
5.
  • Farley, K.A., et al. (författare)
  • In situ radiometric and exposure age dating of the martian surface
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
  • Tidskriftsartikel (refereegranskat)abstract
    • We determined radiogenic and cosmogenic noble gases in a mudstone on the floor of Gale Crater. A K-Ar age of 4.21 ± 0.35 billion years represents a mixture of detrital and authigenic components and confirms the expected antiquity of rocks comprising the crater rim. Cosmic-ray-produced 3He, 21Ne, and 36Ar yield concordant surface exposure ages of 78 ± 30 million years. Surface exposure occurred mainly in the present geomorphic setting rather than during primary erosion and transport. Our observations are consistent with mudstone deposition shortly after the Gale impact or possibly in a later event of rapid erosion and deposition. The mudstone remained buried until recent exposure by wind-driven scarp retreat. Sedimentary rocks exposed by this mechanism may thus offer the best potential for organic biomarker preservation against destruction by cosmic radiation.
  •  
6.
  • Fedirko, V., et al. (författare)
  • Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans
  • 2013
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:2, s. 543-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. Patients and methods: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Results: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Conclusions: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
  •  
7.
  • Sandeman, S., et al. (författare)
  • Characterising Nanoporous Carbon Adsorbents for Biological Application to Chronic Kidney Disease
  • 2012
  • Ingår i: Journal of Biomaterials and Tissue Engineering. - : American Scientific Publishers. - 2157-9083 .- 2157-9091. ; 2:1, s. 40-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The study characterises a range of advanced MAST carbons derived from pyrolysed porous phenolic resins for use in biological applications, considering how the porosity of the carbons impacts both the methods used to assess potential cytotoxicity and the removal of biological molecules relevant to kidney disease. The large surface area and pore volume available for adsorption make both the microporous and the mesoporous MAST carbons suitable for creatinine removal but not for removal of the small but highly water soluble urea. However, only the highly adsorbent MAST carbons with meso- and macroporosity were able to remove the high molecular weight inflammatory cytokine IL-6. It is the adsorption of the larger biological toxins, represented by IL-6 in this study and not removed by purely microporous carbons or in current haemodialysis therapy, which could most significantly contribute to the augmentation of current haemoperfusion therapy.
  •  
8.
  •  
9.
  • Andrade, S. C. S., et al. (författare)
  • Disentangling ribbon worm relationships: multi-locus analysis supports traditional classification of the phylum Nemertea
  • 2012
  • Ingår i: Cladistics. - : Wiley. - 0748-3007. ; 28:2, s. 141-159
  • Tidskriftsartikel (refereegranskat)abstract
    • The phylogenetic relationships of selected members of the phylum Nemertea are explored by means of six markers amplified from the genomic DNA of freshly collected specimens (the nuclear 18S rRNA and 28S rRNA genes, histones H3 and H4, and the mitochondrial genes 16S rRNA and cytochrome c oxidase subunit I). These include all previous markers and regions used in earlier phylogenetic analyses of nemerteans, therefore acting as a scaffold to which one could pinpoint any previously published study. Our results, based on analyses of static and dynamic homology concepts under probabilistic and parsimony frameworks, agree in the non-monophyly of Palaeonemertea and in the monophyly of Heteronemerta and Hoplonemertea. The position of Hubrechtella and the Pilidiophora hypothesis are, however, sensitive to analytical method, as is the monophyly of the non-hubrechtiid palaeonemerteans. Our results are, however, consistent with the main division of Hoplonemertea into Polystilifera and Monostilifera, the last named being divided into Cratenemertea and Distromatonemertea, as well as into the main division of Heteronemertea into Baseodiscus and the remaining species. The study also continues to highlight the deficient taxonomy at the family and generic level within Nemertea and sheds light on the areas of the tree that require further refinement.
  •  
10.
  • Birke-Sorensen, H., et al. (författare)
  • Evidence-based recommendations for negative pressure wound therapy: Treatment variables (pressure levels, wound filler and contact layer) - Steps towards an international consensus
  • 2011
  • Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1878-0539 .- 1748-6815. ; 64, s. 1-16
  • Forskningsöversikt (refereegranskat)abstract
    • Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in many clinical settings. New devices and dressings are being introduced. Despite widespread adoption, there remains uncertainty regarding several aspects of NPWT use. To respond to these gaps, a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In a previous communication, we have reviewed the evidence base for the use of NPWT within trauma and reconstructive surgery. In this communication, we present results of the assessment of evidence relating to the different NPWT treatment variables: different wound fillers (principally foam and gauze); when to use a wound contact layer; different pressure settings; and the impact of NPWT on bacterial bioburden. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence and drafting of the recommendations by a global expert panel. Evidence and recommendations were graded according to the Scottish Intercollegiate Guidelines Network (SIGN) classification system. In general, there is relatively weak evidence on which to base recommendations for any one NPWT treatment variable over another. Overall, 14 recommendations were developed: five for the choice of wound filler and wound contact layer, four for choice of pressure setting and five for use of NPWT in infected wounds. With respect to bioburden, evidence suggests that reduction of bacteria in wounds is not a major mode of action of NPWT. (C) 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
  •  
11.
  • Grotzinger, J.P., et al. (författare)
  • A habitable fluvio-lacustrine environment at Yellowknife Bay, Gale Crater, Mars
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
  • Tidskriftsartikel (refereegranskat)abstract
    • The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred to represent an ancient lake and preserve evidence of an environment that would have been suited to support a martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen, sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements; by inference, phosphorus is assumed to have been available. The environment probably had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars.
  •  
12.
  • Gullbo, Joachim, et al. (författare)
  • Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment
  • 2011
  • Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 82:2, s. 139-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary cultures of patient tumor cells (PCPTC) have been used for prediction of diagnosis-specific activity and individual patient response to anticancer drugs, but have not been utilized as a model for identification of novel drugs in high throughput screening. In the present study, ovarian carcinoma cells from three patients were tested in response to a library of 3000 chemically diverse compounds. Eight hits were retrieved after counter screening using normal epithelial cells, and one of the two structurally related hit compounds was selected for further preclinical evaluation. This compound, designated VLX 50, demonstrated a broad spectrum of activity when tested in a panel of PCPTCs representing different forms of leukemia and solid tumors and displayed a high tumor to normal cell activity. VLX 50 induced delayed cell death with some features of classical apoptosis. Significant in vivo activity was confirmed on primary cultures of human ovarian carcinoma cells in mice using the hollow fiber model. Mechanistic exploration was performed using gene expression analysis of drug exposed tumor cells to generate a drug-specific signature. This query signature was analyzed using the Gene Set Enrichment Analysis and the Connectivity Map database. Strong connections to hypoxia inducible factor 1 and iron chelators were retrieved. The mechanistic hypothesis of intracellular iron depletion leading to hypoxia signaling was confirmed by a series of experiments. The results indicate the feasibility of using PCPTC for cancer drug screening and that intracellular iron depletion could be a potentially important strategy for cancer therapy.
  •  
13.
  • Lindgren, Hanna S., et al. (författare)
  • Putaminal Upregulation of FosB/ΔFosB-Like Immunoreactivity in Parkinson's Disease Patients with Dyskinesia
  • 2011
  • Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:4, s. 347-357
  • Tidskriftsartikel (refereegranskat)abstract
    • The transcription factor FosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson´s disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and FosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/ FosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/ FosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/ FosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/ FosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of FosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.
  •  
14.
  • Rinaldi, S, et al. (författare)
  • Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women : a cross-sectional study within the EPIC cohort
  • 2014
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 25:1, s. 111-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was < 2 %. Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.
  •  
15.
  • Runkel, N., et al. (författare)
  • Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: Steps towards an international consensus
  • 2011
  • Ingår i: Injury. - 1879-0267. ; 42:Suppl. 1, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone. (C) 2011 Elsevier Ltd. All rights reserved.
  •  
16.
  • Vig, S., et al. (författare)
  • Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: Steps towards an international consensus
  • 2011
  • Ingår i: Journal of Tissue Viability. - : Elsevier BV. - 1876-4746 .- 0965-206X. ; 20, s. 1-18
  • Forskningsöversikt (refereegranskat)abstract
    • Aim: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. Methods: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Results: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. Conclusion: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone. (c) 2011 Published by Elsevier Ltd on behalf of Tissue Viability Society.
  •  
17.
  • ANDRADE, S.C.S, et al. (författare)
  • A transcriptomic approach to ribbon worm systematics (Nemertea): resolving the Pilidiophora problem.
  • 2014
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 31:12, s. 3206-3215
  • Tidskriftsartikel (refereegranskat)abstract
    • Resolving the deep relationships of ancient animal lineages has proven difficult using standard Sanger-sequencing approaches with a handful of markers. We thus reassess the relatively well-studied phylogeny of the phylum Nemertea (ribbon worms)—for which the targeted gene approaches had resolved many clades but had left key phylogenetic gaps—by using a phylogenomic approach using Illumina-based de novo assembled transcriptomes and automatic orthology prediction methods. The analysis of a concatenated data set of 2,779 genes (411,138 amino acids) with about 78% gene occupancy and a reduced version with 95% gene occupancy, under evolutionary models accounting or not for site-specific amino acid replacement patterns results in a well-supported phylogeny that recovers all major accepted nemertean clades with the monophyly of Heteronemertea, Hoplonemertea, Monostilifera, being well supported. Significantly, all the ambiguous patterns inferred from Sanger-based approaches were resolved, namely the monophyly of Palaeonemertea and Pilidiophora. By testing for possible conflict in the analyzed supermatrix, we observed that concatenation was the best solution, and the results of the analyses should settle prior debates on nemertean phylogeny. The study highlights the importance, feasibility, and completeness of Illumina-based phylogenomic data matrices.
  •  
18.
  • Beecham, Ashley H, et al. (författare)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
  •  
19.
  • Bhoo-Pathy, Nirmala, et al. (författare)
  • Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer : Results From the European Prospective Investigation into Nutrition and Cancer Study
  • 2013
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 11:11, s. 1486-1492
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer.METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire, and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression.RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers.CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.
  •  
20.
  • Duell, E. J., et al. (författare)
  • Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2164-2175
  • Tidskriftsartikel (refereegranskat)abstract
    • Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort. What's new Because the incidence of pancreatic cancer is 30-50% higher in men than women, researchers have wondered whether exposure to estrogen might offer a protective effect. The answer thus far has been unclear, however. In this study, the authors examined menstrual and reproductive factors in women, as well as exogenous hormone use. They also examined variants of the CYP17A1 gene in both women and men, as this gene is essential for sex-steroid metabolism. Only early age of menarche showed any association with pancreatic cancer risk. Copyright © 2012 UICC.
  •  
21.
  • Fedirko, V., et al. (författare)
  • Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2013
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:8, s. 2166-2173
  • Tidskriftsartikel (refereegranskat)abstract
    • While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations. The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case-control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured. HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74-0.95 and HR = 0.80, 95% CI 0.69-0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66-1.11 and RR = 0.74, 95% CI 0.50-1.09, respectively) in a nested case-control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk. In this large European cohort, total fish intake is associated with lower HCC risk.
  •  
22.
  • Fedirko, V., et al. (författare)
  • Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study
  • 2014
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 60:4, s. 1222-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. © 2014 by the American Association for the Study of Liver Diseases.
  •  
23.
  • Jacobs, Eric J, et al. (författare)
  • Family history of cancer and risk of pancreatic cancer : A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).
  • 2010
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215.
  • Tidskriftsartikel (refereegranskat)abstract
    • A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.
  •  
24.
  • Kajihara, H., et al. (författare)
  • Taxonomic Identity of a Tetrodotoxin-Accumulating Ribbon-worm Cephalothrix simula (Nemertea: Palaeonemertea): A Species Artificially Introduced from the Pacific to Europe
  • 2013
  • Ingår i: Zoological Science. - : Zoological Society of Japan. - 0289-0003. ; 30:11, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • We compared the anatomy of the holotype of the palaeonemertean Cephalothrix simula (Iwata, 1952) with that of the holotypes of Cephalothrix hongkongiensis Sundberg, Gibson and Olsson, 2003 and Cephalothrix fasciculus (Iwata, 1952), as well as additional specimens from Fukue (type locality of C. simula) and Hiroshima, Japan. While there was no major morphological discordance between these specimens, we found discrepancies between the actual morphology and some statements in the original description of C. simula with respect to supposedly species-specific characters. Our observation indicates that these three species cannot be discriminated by the anatomical characters so far used to distinguish congeners. For objectivity of scientific names, topogenetypes of the mitochondrial cytochrome c oxidase subunit I (COI) sequences are designated for C. simula, C. hongkongiensis, and C. fasciculus. Analysis of COI sequence showed that the Hiroshima population can be identified as C. simula, which has been found in previous studies from Trieste, Italy, and also from both the Mediterranean and Atlantic coasts of the Iberian Peninsula, indicating an artificial introduction via (1) ballast water, (2) ship-fouling communities, or (3) the commercially cultured oyster Crassostrea gigas (Thunberg, 1793) brought from Japan to France in 1970s. Cephalothrix simula is known to be toxic, as it contains large amounts of tetrodotoxin (TTX). We report here that the grass puffer Takifugu niphobles (Jordan and Snyder, 1901)-also known to contain TTX-consumes C. simula. We suggest that the puffer may be able to accumulate TTX by eating C. simula.
  •  
25.
  • Levin, Malin, 1973, et al. (författare)
  • Evaluation of macrophage-specific promoters using lentiviral delivery in mice.
  • 2012
  • Ingår i: Gene therapy. - : Springer Science and Business Media LLC. - 1476-5462 .- 0969-7128. ; 19:11, s. 1041-7
  • Tidskriftsartikel (refereegranskat)abstract
    • In gene therapy, tissue-specific promoters are useful tools to direct transgene expression and improve efficiency and safety. Macrophage-specific promoters (MSPs) have previously been published using different delivery systems. In this study, we evaluated five different MSPs fused with green fluorescent protein (GFP) to delineate the one with highest specificity using lentiviral delivery. We compared three variants of the CD68 promoter (full length, the 343-bp proximal part and the 150-bp proximal part) and two variants (in forward and reverse orientation) of a previously characterized synthetic promoter derived from elements of transcription factor genes. We transduced a number of cell lines and primary cells in vitro. In addition, hematopoietic stem cells were transduced with MSPs and transferred into lethally irradiated recipient mice. Fluorescence activated cell sorting analysis was performed to determine the GFP expression in different cell populations both in vitro and in vivo. We showed that MSPs can efficiently be used for lentiviral gene delivery and that the 150-bp proximal part of the CD68 promoter provides primarily macrophage-specific expression of GFP. We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors.
  •  
26.
  • Löwemark, Ludvig, et al. (författare)
  • Normalizing XRF-scanner data : A cautionary note on the interpretation of high-resolution records from organic-rich lakes
  • 2011
  • Ingår i: Journal of Asian Earth Sciences. - : Elsevier BV. - 1367-9120 .- 1878-5786. ; 40:6, s. 1250-1256
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray fluorescence (XRF) scanning of unlithified, untreated sediment cores is becoming an increasingly common method used to obtain paleoproxy data from lake records. XRF-scanning is fast and delivers high-resolution records of relative variations in the elemental composition of the sediment. However, lake sediments display extreme variations in their organic matter content, which can vary from just a few percent to well over 50%. As XRF scanners are largely insensitive to organic material in the sediment, increasing levels of organic material effectively dilute those components that can be measured, such as the lithogenic material (the closed-sum effect). Consequently, in sediments with large variations in organic material, the measured variations in an element will to a large extent mirror the changes in organic material. It is therefore necessary to normalize the elements in the lithogenic component of the sediment against a conservative element to allow changes in the input of the elements to be addressed. In this study we show that Al, which is the lightest element that can be measured using the Wax XRF-scanner, can be used to effectively normalize the elements of the lithogenic fraction of the sediment against variations in organic content. We also show that care must be taken when choosing resolution and exposure time to ensure optimal output from the measurements.
  •  
27.
  • Margalef, O., et al. (författare)
  • Environmental processes in Rano Aroi (Easter Island) peat geochemistry forced by climate variability during the last 70 kyr
  • 2014
  • Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 414, s. 438-450
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyze the geochemistry of Rano Aroi mire record (Easter Island) using bulk peat composition (C, N, S) and stable isotopes (delta C-13, delta N-15, delta S-34) and major, minor and trace elemental compositions obtained by ICP-AES (Al, Ti, Zr, Sc, V, Y, Fe, Mn, Th, Ba, Ca, Mg and Sr). Peat geochemistry and the pollen record are used to reconstruct the environmental changes during the last 70 kyr BP. Principal component analysis on ICP-AES data revealed that three main components account for the chemical signatures of the peat. The first component, characterized by lithogenic elements (combined signal of V. Al, Sc, Y, Cr, Cd, Ti, Zr and Cu), evidences long-term changes in the basal fluxes of mineral material into the mire. This component, in combination with stable isotopes and pollen data suggests a link between soil erosion and vegetation cover changes in the Rano Aroi watershed. The second component is identified by the signal of Fe, Mn, Th, Ba, Zr and Ti, and is indicative of strong runoff events during enhanced precipitation periods. The third component (tied mainly to Ca, Sr and Mg) reflects a strong peat oxidation event that occurred during an arid period with more frequent droughts, sometime between 39 and 31 kyr BP. Correlation coefficients and a multiple regression model (PCR analysis) between peat organic chemistry and the principal components of ICP-AES analysis were calculated. Isotope chemistry of the peat organic matter further contributes to define Rano Aroi environmental history: delta C-13 data corroborates a vegetation shift documented by the palynological record from C-4 to C-3 between 55 and 45 cal kyr BP; the delta N-15 record identifies periods of changes in mire productivity and denitrification processes, while the delta S-34 peat signature indicates a marine origin of S and significant diagenetic cycling. The geochemical and environmental evolution of Rano Aroi mire is coherent with the regional climatic variability and suggests that climate was the main forcing in mire evolution during the last 70 kyr BP. The coupling of geochemical and biological proxies improves our ability to decipher depositional processes in tropical and subtropical peatlands and to use these sequences for paleoenvironmental and paleoclimate reconstructions.
  •  
28.
  •  
29.
  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
  •  
30.
  • Schlesinger, S, et al. (författare)
  • Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort
  • 2013
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2449-2455
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.
  •  
31.
  • Schütte, André, et al. (författare)
  • Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus
  • 2014
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:34, s. 12396-12401
  • Tidskriftsartikel (refereegranskat)abstract
    • The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel-forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a two-layered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin β-deficient mice was now found to be attached. Meprin β is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin β was added to the attached mucus of meprin β-deficient mice, the mucus was detached from the epithelium. Similar to meprin β-deficient mice, germ-free mice have attached mucus as they did not shed the membrane-anchored meprin β into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin β to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin β cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin β in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding.
  •  
32.
  • Wolpin, Brian M., et al. (författare)
  • Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:9, s. 994-
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
  •  
33.
  • Andre, Alann, et al. (författare)
  • An experimental and numerical study of the effect of some manufacturing defects
  • 2013
  • Ingår i: ICCM International Conferences on Composite Materials. - : International Committee on Composite Materials. ; , s. 4105-4112
  • Konferensbidrag (refereegranskat)abstract
    • During the manufacturing process of composite structural parts, layer of fabrics or unidirectional prepreg may have to be cut in order to fulfil production requirements. From a general mechanical point of view, cutting fibres in a composite part has a large negative impact on the mechanical properties. However, such interventions are necessary in particular cases, for example due to draping of complex geometries. A rather extensive test program was launched to investigate the effects of defects that typically could arise during manufacturing. The overall purpose of the test program was to determine knock-down factors on strength for typical manufacturing defects that occasionally arise and sometimes are hard to avoid in production: cuts/gaps and fibre angle deviations. Four types of specimens were tested, reference, intersection of cuts in adjacent layers combined with a bolt hole, cut in a zero degree ply combined with a bolt hole and specimens with misaligned fibres. The specimens with misaligned fibres were tested with three different fibre angles. In addition to the experimental procedure, FE-analyses utilising cohesive elements were conducted, and after mechanical tests, Non Destructive Investigation (NDI) and fractographic investigations were performed. An excellent correlation between analyses and experiments were obtained. 
  •  
34.
  • Annborn, Martin, et al. (författare)
  • CT-proAVP (copeptin), MR-proANP and Peroxiredoxin 4 after cardiac arrest: release profiles and correlation to outcome.
  • 2014
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:4, s. 428-436
  • Tidskriftsartikel (refereegranskat)abstract
    • Further characterization of the post-cardiac arrest syndrome (PCAS) is essential to better understand the mechanisms resulting in injury and death. We investigated serial serum concentrations of the stress hormone c-terminal provasopressin (CT-proAVP or copeptin), the cardiac biomarker MR-proANP and a biomarker of oxidation injury, Peroxiredoxin 4 (Prx4) in patients treated with mild hypothermia (MHT) after cardiac arrest, and studied their association to the PCAS and long-term outcome.
  •  
35.
  • Asad, Samina, et al. (författare)
  • HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
  •  
36.
  • Beckham, Gregg T., et al. (författare)
  • The O-Glycosylated Linker from the Trichoderma reesei Family 7 Cellulase Is a Flexible, Disordered Protein
  • 2010
  • Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:11, s. 3773-3781
  • Tidskriftsartikel (refereegranskat)abstract
    • Fungi and bacteria secrete glycoprotein cocktails to deconstruct cellulose Cellulose degrading enzymes (cellulases) are often modular with catalytic domains for cellulose hydrolysis and carbohydrate binding modules connected by linkers rich in serine and threonine with O-glycosylation Few studies have probed the role that the linker and O-glycans play in catalysis Since different expression and growth conditions produce different glycosylation patterns that affect enzyme activity the structure function relationships that glycosylation imparts to linkers are relevant for understanding cellulase mechanisms Here the linker of the Trichoderma reesei Family 7 cellobiohydrolase (Cel7A) is examined by simulation Our results suggest that the Cel7A linker is an intrinsically disordered protein with and without glycosylation Contrary to the predominant view the O-glycosylation does not change the stiffness of the linker as measured by the relative fluctuations in the end to end distance rather it provides a 16 A extension thus expanding the operating range of Cel7A We explain observations from previous biochemical experiments in the light of results obtained here and compare the Cel7A linker with linkers from other cellulases with sequence based tools to predict disorder This preliminary screen indicates that linkers from Family 7 enzymes from other genera and other cellulases within T reesei may not be as disordered warranting further study
  •  
37.
  • Benedict, Christian, et al. (författare)
  • Acute Sleep Deprivation Enhances the Brain's Response to Hedonic Food Stimuli : An fMRI Study
  • 2012
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:3, s. E443-447
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown.Objective:Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food.Intervention:Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan.Main Outcome Measures:Compared with sleep, total sleep deprivation was associated with an increased activation in the right anterior cingulate cortex in response to food images, independent of calorie content and prescan hunger ratings. Relative to the postsleep condition, in the total sleep deprivation condition, the activation in the anterior cingulate cortex evoked by foods correlated positively with postscan subjective appetite ratings. Self-reported hunger after the nocturnal vigil was enhanced, but importantly, no change in fasting plasma glucose concentration was found.Conclusions:These results provide evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels. These findings highlight a potentially important mechanism contributing to the growing levels of obesity in Western society.
  •  
38.
  • Campa, Daniele, et al. (författare)
  • A genome-wide "pleiotropy scan'' does not identify new susceptibility loci for estrogen receptor negative breast cancer
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e85955-
  • Tidskriftsartikel (refereegranskat)abstract
    • Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER- positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER- negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to perform a secondary analysis of an ER- negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER- GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 x 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach''.
  •  
39.
  • Carling, Malin S, et al. (författare)
  • Preoperative Fibrinogen Plasma Concentration Is Associated With Perioperative Bleeding and Transfusion Requirements in Scoliosis Surgery.
  • 2011
  • Ingår i: Spine. - 1528-1159. ; 36:7, s. 549-55
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY DESIGN.: Prospective observational study. OBJECTIVE.: To investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery. SUMMARY OF BACKGROUND DATA.: Bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. Early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk. METHODS.: A total of 82 otherwise healthy patients (mean age: 15 ± 3 years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. Patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. Correlations between laboratory variables and bleeding volume were calculated with Pearson test. Patient variables and laboratory variables were compared with Student t test between patients with bleeding volume in the upper quartile ("bleeders") and the remaining patients, and between patients with extensive transfusion (defined as >2 U of packed red cells) and no or limited transfusions (≤2 U). RESULTS.: Mean fibrinogen concentration was 3.0 ± 0.7 g/L (range, 1.3-4.9). Mean total perioperative bleeding volume was 1552 ± 1019 mL (range, 100-5800 mL). Total bleeding volume correlated significantly with preoperative fibrinogen concentration (r = -0.31, P = 0.005) but neither with platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 ± 0.6 vs. 3.1 ± 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were transfused with >2 U of packed red cells.Patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 ± 0.7 vs. 3.1 ± 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT did not differ. CONCLUSION.: The results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. Preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.
  •  
40.
  • Chawchai, Sakonvan, et al. (författare)
  • Lake Kumphawapi - an archive of Holocene palaeoenvironmental and palaeoclimatic changes in northeast Thailand
  • 2013
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 68, s. 59-75
  • Tidskriftsartikel (refereegranskat)abstract
    • The long-term climatic and environmental history of Southeast Asia, and of Thailand in particular, is still fragmentary. Here we present a new C-14-dated, multi-proxy sediment record (TOC, C/N, CNS isotopes, Si, Zr, K, Ti, Rb, Ca elemental data, biogenic silica) for Lake Kumphawapi, the second largest natural lake in northeast Thailand. The data set provides a reconstruction of changes in lake status, groundwater fluctuations, and catchment run-off during the Holocene. A comparison of multiple sediment sequences and their proxies suggests that the summer monsoon was stronger between c. 9800 and 7000 cal yr BP. Lake status and water level changes around 7000 cal yr BP signify a shift to lower effective moisture. By c. 6500 cal yr BP parts of the lake had been transformed into a peatland, while areas of shallow water still occupied the deeper part of the basin until c. 5400-5200 cal yr BP. The driest interval in Kumphawapi's history occurred between c. 5200 and 3200 cal yr BP, when peat extended over large parts of the basin. After 3200 cal yr BP, the deepest part of the lake again turned into a wetland, which existed until c. 1600 cal yr BP. The observed lake-level rise after 1600 cal yr BP could have been caused by higher moisture availability, although increased human influence in the catchment cannot be ruled out. The present study highlights the use of multiple sediment sequences and proxies to study large lakes, such as Lake Kumphawapi in order to correctly assess the time transgressive response to past changes in hydroclimate conditions. Our new data set from northeast Thailand adds important palaeoclimatic information for a region in Southeast Asia and allows discussing Holocene monsoon variability and ITCZ movement in greater detail.
  •  
41.
  • Chen, Hai-Xia, et al. (författare)
  • Statistical parsimony networks and species assemblages in cephalothricid nemerteans (Nemertea).
  • 2010
  • Ingår i: PLoS ONE. - 1932-6203. ; 5:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It has been suggested that statistical parsimony network analysis could be used to get an indication of species represented in a set of nucleotide data, and the approach has been used to discuss species boundaries in some taxa. METHODOLOGY/PRINCIPAL FINDINGS: Based on 635 base pairs of the mitochondrial protein-coding gene cytochrome c oxidase I (COI), we analyzed 152 nemertean specimens using statistical parsimony network analysis with the connection probability set to 95%. The analysis revealed 15 distinct networks together with seven singletons. Statistical parsimony yielded three networks supporting the species status of Cephalothrix rufifrons, C. major and C. spiralis as they currently have been delineated by morphological characters and geographical location. Many other networks contained haplotypes from nearby geographical locations. Cladistic structure by maximum likelihood analysis overall supported the network analysis, but indicated a false positive result where subnetworks should have been connected into one network/species. This probably is caused by undersampling of the intraspecific haplotype diversity. CONCLUSIONS/SIGNIFICANCE: Statistical parsimony network analysis provides a rapid and useful tool for detecting possible undescribed/cryptic species among cephalotrichid nemerteans based on COI gene. It should be combined with phylogenetic analysis to get indications of false positive results, i.e., subnetworks that would have been connected with more extensive haplotype sampling.
  •  
42.
  • Chuang, Shu-Chun, et al. (författare)
  • A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition
  • 2011
  • Ingår i: European Journal of Cancer. - Oxford : Pergamon. - 0959-8049 .- 1879-0852. ; 47:12, s. 1808-1816
  • Tidskriftsartikel (refereegranskat)abstract
    • Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.
  •  
43.
  • Evans, Juliet, et al. (författare)
  • Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity
  • 2011
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 74:1, s. 51-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective  It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women. Design and methods  S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m(2) ) and obese (BMI >30 kg/m(2) ) black (n = 30) and white (n = 26) South African women. Results  Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05). Conclusions  Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.
  •  
44.
  • Ghorbanzadeh, Mehdi, et al. (författare)
  • In vitro and in silico derived relative effect potencies of Ah-Receptor-mediated effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX Cell Lines
  • 2014
  • Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 27:7, s. 1120-1132
  • Tidskriftsartikel (refereegranskat)abstract
    • For a better understanding of species-specific relative effect potencies (REPs), responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated using chemical-activated luciferase gene expression assays (CALUX) derived from guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the rodent cell lines were partial agonists and less efficacious than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for each congener using concentrations at which 20% of the maximal TCDD response was reached,(REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with their toxic equivalency factors assigned by the World Health Organization (WHO-TEF), while those for PCBs were in general lower than the WHO-TEF values. Moreover, the guinea pig cell line was the most sensitive as indicated by the 20% effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and mouse cells, respectively. A similar response pattern was observed using multivariate statistical analysis between the three CALLTX assays and the WHO-TEFs. The mouse assay showed minor deviation due to higher relative induction potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8-hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was more than two times more potent in the mouse assay as compared with that of rat and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In order to provide REP20TCDD values for all WHO-TEF assigned compounds, quantitative structure activity relationship (QSAR) models were developed. The QSAR models showed that specific electronic properties and molecular surface characteristics play important roles in the AhR-mediated response. In silica derived REP20TCDD values were generally consistent with the WHO-TEFs with a few exceptions. The QSAR models indicated that, e.g., 1,2,3,7,8-pentachlorodibenzofuran and 1,2,3,7,8,9-hexachlorodibenzofuran were more potent than given by their assigned WHO-TEF values, and the non-ortho PCB 81 was predicted, based on the guinea-pig model, to be 1 order of magnitude above its WHO-TEF value. By combining in vitro and in silico approaches, REPs were established for all WHO-TEF assigned compounds (except OCDD), which will provide future guidance in testing AhR-mediated responses of DLCs and to increase our understanding of species variation in AhR-mediated effects.
  •  
45.
  • Grote, Verena A., et al. (författare)
  • The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort
  • 2012
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130, s. 2428-2437
  • Tidskriftsartikel (refereegranskat)abstract
    • Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development. © 2011 UICC.
  •  
46.
  • Johansson, Malin E V, 1971, et al. (författare)
  • Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis.
  • 2014
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 63:2, s. 281-291
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? METHODS AND RESULTS: The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10(-/-) mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. CONCLUSIONS: Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.
  •  
47.
  • Leenders, Max, et al. (författare)
  • Plasma cotinine levels and pancreatic cancer in the EPIC cohort study
  • 2012
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:4, s. 997-1002
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (595% range: 2.812.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self-reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.111.60]. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.449.26). The results for self-reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.0216.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.
  •  
48.
  • Löfving, Malin E S, 1979, et al. (författare)
  • Leadership style, organization culture and manufacturing strategy formulation - Empirical evidence from Swedish SMEs
  • 2013
  • Ingår i: Proceedings of 22nd International Conference on Production Research, CPR 2013, Parana, Brazil, 28 July - 1 August 2013. - 9788588478473
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents findings from an empirical study of manufacturing strategy formulation processes in three SMEs. The study investigated the relationship between manufacturing strategy formulation, leadership style, and organisation culture. The three companies had different formulation processes. One tentative explanation for this is due to leadership style and the personalised management that characterises SMEs. The investigation indicates that the two of the companies that had a power culture were more mature considering strategic work, and acted on more competitively exposed markets than the company with a support culture.
  •  
49.
  • Löfving, Malin E S, 1979 (författare)
  • Manufacturing strategy formulation in small and medium-sized enterprises
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Small and medium-sized enterprises (SMEs) are the backbone of any national economy and key drivers for economic growth. To sustain their competitiveness, it is essential that SMEs take advantage of their capabilities and support market requirements. This research encourages an increased focus on work with manufacturing strategies in SMEs. The purpose of this research is to increase our understanding of manufacturing strategy formulation in SMEs. To provide SMEs with useful advice on how to work with manufacturing strategies, this research focuses on internal and external key factors that are considered to be significant for manufacturing strategy formulation in SMEs. Manufacturing strategy formulation was investigated in three case studies in Sweden and two supplementary case studies in Singapore. The results in this research are presented in six papers and are encapsulated and extended in the summarising chapters of the compilation thesis. Internal key factors for manufacturing strategy formulation are mainly identified from the literature about larger companies and are categorised in the following ways: procedure (what should be done), alignment (consistency between strategies, manufacturing strategies and manufacturing decisions), management (how the formulation is managed) and realisation (how the formulations are executed). The internal key factors seem to be of general value for all kinds of companies, but how the internal key factors are reflected in each individual company’s manufacturing strategy formulations may vary due to the characteristics that SMEs exhibit. The internal key factors are synthesised into a model that provides practical guidance for manufacturing strategy formulation and aims at facilitating learning in SMEs through a structured way of working. External key factors are addressed in two of the appended papers and the influence of these factors is further analysed in the summarising chapters. The external key factors identified were macro environment, industry, supplier, competitive environment and national culture. Two of these external key factors, competitive environment and national culture, were found to be more influential for manufacturing strategy formulation in SMEs.
  •  
50.
  • Löfving, Malin E S, 1979, et al. (författare)
  • Manufacturing strategy formulation process - evidence from SMEs
  • 2012
  • Ingår i: Proceedings of the 4th World Conference on Production & Operations Management, Amsterdam, Netherlands, July 1-5. - : International Annual EurOMA Conference.
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents an empirical study of the formulation process of manufacturing strategies using a conceptual framework in small and medium-sized manufacturing enterprises. SMEs are known to have an informal and unintentional strategy formulation process and this study shows that SMEs can benefit using guidance in the manufacturing strategy formulation process. The conceptual framework provided a structure, which facilitates the understanding and the way of working. Other benefits are a closer dialogue between different functions of a company, a shared view in the organisation of improvements in manufacturing and a common view of their competitive priorities.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 79
Typ av publikation
tidskriftsartikel (63)
konferensbidrag (11)
forskningsöversikt (2)
rapport (1)
bok (1)
doktorsavhandling (1)
visa fler...
visa färre...
Typ av innehåll
refereegranskat (75)
övrigt vetenskapligt/konstnärligt (4)
Författare/redaktör
Sund, Malin, 1972- (19)
Lindkvist, Björn (12)
Löfving, Malin E S, ... (12)
Overvad, K (11)
Riboli, E. (11)
Winroth, Mats, 1956- (11)
visa fler...
Khaw, Kay-Tee (10)
Tumino, R. (10)
Overvad, Kim (9)
Boutron-Ruault, Mari ... (9)
Kaaks, Rudolf (9)
Riboli, Elio (9)
Boeing, H. (9)
Khaw, K. T. (9)
Säfsten, Kristina (9)
Palli, D (9)
Peeters, Petra H. M. (9)
Duell, Eric J. (9)
Jenab, M (9)
Johansen, Dorthe (9)
Boeing, Heiner (8)
Trichopoulou, Antoni ... (8)
Tumino, Rosario (8)
Bueno-de-Mesquita, H ... (8)
Jenab, Mazda (8)
Trichopoulou, A (8)
Clavel-Chapelon, Fra ... (7)
Kaaks, R. (7)
Palli, Domenico (7)
Panico, Salvatore (7)
Vineis, Paolo (7)
Bueno-de-Mesquita, H ... (7)
Trichopoulos, Dimitr ... (7)
Ye, Weimin (7)
Panico, S (7)
Amiano, P. (6)
Vineis, P (6)
Tjonneland, Anne (6)
Tjønneland, A (6)
Weiderpass, E (5)
Tjønneland, Anne (5)
Ardanaz, E. (5)
Clavel-Chapelon, F. (5)
Molina-Montes, E. (5)
Quiros, J. R. (5)
Canzian, Federico (5)
Larranaga, Nerea (5)
Molina-Montes, Esthe ... (5)
Sundberg, Per, 1950 (5)
Sánchez, M-J (5)
visa färre...
Lärosäte
Umeå universitet (28)
Karolinska Institutet (28)
Göteborgs universitet (25)
Lunds universitet (24)
Chalmers tekniska högskola (15)
Jönköping University (10)
visa fler...
Uppsala universitet (6)
Kungliga Tekniska Högskolan (4)
Stockholms universitet (4)
Luleå tekniska universitet (3)
Örebro universitet (3)
Linköpings universitet (3)
RISE (2)
Sveriges Lantbruksuniversitet (2)
Linnéuniversitetet (1)
Högskolan Dalarna (1)
Marie Cederschiöld högskola (1)
visa färre...
Språk
Engelska (77)
Svenska (2)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (46)
Teknik (17)
Naturvetenskap (12)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy