| 1. |
- Ameur, Adam, et al.
(författare)
-
SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
-
Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
-
Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
|
|
| 2. |
- Jemt, Anders, 1985-, et al.
(författare)
-
Evaluation of methods for whole genome and transcriptome sequencing from nanograms of FFPE samples
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The most widely used method for the preservation of clinical tissue specimens is formalin fixation and paraffin embedding (FFPE). Simultaneous analysis of RNA and DNA from samples preserved using this method have long proved problematic, primarily due to lack of material. Here, we describe an attempt to build a complete analysis package for RNA and DNA extracted from single tissue sections. The workflow includes quality control of the extracted material, library preparation and data analysis. We extract DNA with varying integrity from FFPE sections and subject them to whole genome sequencing using two library preparation methods, Illumina TruSeq Nano using the Illumina NeoPrep and Rubicon Genomics ThruPlex. We are able to obtain some usable data, albeit with high duplication rates, demonstrating both the possibilities and challenges of sequencing damaged DNA. Two different approaches to transcriptome sequencing are assessed, the TruSeq RNA Access library preparation kit from Illumina and the SMARTer Stranded Total RNA-Seq Kit - Pico Input from Clonetech. The sequence capture approach of the TruSeq kit is shown to be more robust to low integrity RNA compared to the SMARTer kit. However, the SMARTer kit needs much less starting material and is able to yield data about all transcripts, not just protein coding mRNA.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Bjelke, Ulf, et al.
(författare)
-
Crustacea : Kräftdjur - crustaceans
- 2010
-
Ingår i: The 2010 Red List of Swedish Species. Rödlistade arter i Sverige 2010. - Uppsala : ArtDatabanken, SLU. - 9789188506351 ; , s. 487-493
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 6. |
- Borgmästars, Emmy, et al.
(författare)
-
Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples
- 2021
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21
-
Tidskriftsartikel (refereegranskat)abstract
- Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
|
|
| 7. |
|
|
| 8. |
- Borgmästars, Emmy, et al.
(författare)
-
Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
-
Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
|
|
| 9. |
- Borgmästars, Emmy, et al.
(författare)
-
Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
-
Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
|
|
| 10. |
- Borgmästars, Emmy, et al.
(författare)
-
Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma : a nested case-control study
- 2024
-
Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 48
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
|
|
| 11. |
- Bylund, Annika, et al.
(författare)
-
Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.
- 2005
-
Ingår i: Experimental biology and medicine. - 1535-3702 .- 1535-3699. ; 230:3, s. 217-223
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.
|
|
| 12. |
- Cust, Anne E, et al.
(författare)
-
The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis : a prospective study.
- 2009
-
Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 113:3, s. 567-576
-
Tidskriftsartikel (refereegranskat)abstract
- It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case–control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II–IV (P heterogeneity all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30–0.78, P trend = 0.004); leptin, 0.64 (95% CI, 0.41–1.00, P trend = 0.06); and HbA1c, 0.47 (95% CI, 0.28–0.80, P trend = 0.005). For stage II–IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression.
|
|
| 13. |
- Fasterius, Erik, et al.
(författare)
-
A novel RNA sequencing data analysis method for cell line authentication
- 2017
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:2
-
Tidskriftsartikel (refereegranskat)abstract
- We have developed a novel analysis method that can interrogate the authenticity of biological samples used for generation of transcriptome profiles in public data repositories. The method uses RNA sequencing information to reveal mutations in expressed transcripts and subsequently confirms the identity of analysed cells by comparison with publicly available cell-specific mutational profiles. Cell lines constitute key model systems widely used within cancer research, but their identity needs to be confirmed in order to minimise the influence of cell contaminations and genetic drift on the analysis. Using both public and novel data, we demonstrate the use of RNA-sequencing data analysis for cell line authentication by examining the validity of COLO205, DLD1, HCT15, HCT116, HKE3, HT29 and RKO colorectal cancer cell lines. We successfully authenticate the studied cell lines and validate previous reports indicating that DLD1 and HCT15 are synonymous. We also show that the analysed HKE3 cells harbour an unexpected KRAS-G13D mutation and confirm that this cell line is a genuine KRAS dosage mutant, rather than a true isogenic derivative of HCT116 expressing only the wild type KRAS. This authentication method could be used to revisit the numerous cell line based RNA sequencing experiments available in public data repositories, analyse new experiments where whole genome sequencing is not available, as well as facilitate comparisons of data from different experiments, platforms and laboratories.
|
|
| 14. |
- Franco, Irene, et al.
(författare)
-
Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.
|
|
| 15. |
- Franco, Irene, et al.
(författare)
-
Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
- 2019
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer. Results: To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Conclusions: Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
|
|
| 16. |
- Franklin, Oskar, et al.
(författare)
-
Plasma micro-RNA alterations appear late in pancreatic cancer
- 2018
-
Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 267:4, s. 775-781
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.
|
|
| 17. |
- Grahn, Oskar, et al.
(författare)
-
Peritoneal infection after colorectal cancer surgery induces substantial alterations in postoperative protein levels : an exploratory study
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis.Methods: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed.Results: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K/Akt) and transforming growth factor beta (TGF-β) signaling.Conclusion: These affected proteins and pathways could provide clues as to why these patients might suffer increased cancer recurrence, mortality and cardiovascular morbidity.
|
|
| 18. |
- Hansson, Pär, et al.
(författare)
-
Exports as an indicator on or promoter of successful Swedish manufacturing firms in the 1990s
- 2004
-
Ingår i: Review of World Economics. - 1610-2878 .- 1610-2886. ; 140:3, s. 415-445
-
Tidskriftsartikel (refereegranskat)abstract
- We study the link between exports and productivity at the firm level. Like in previous studies we get support for the hypothesis that more productive firms self-select into the export market. In addition, and contrary to many of the former studies, we also obtain evidence that exporting further increases firm productivity. Exporting firms appear to have significantly higher productivity than nonexporting. Moreover, exporters—mainly firms that increase their export intensities—have higher output growth than nonexporters. Reallocation of resources between firms may then have contributed to overall manufacturing productivity growth. Hence, we try to quantify the importance of reallocation.
|
|
| 19. |
- Helgadottir, Hafdis, et al.
(författare)
-
Somatic mutation that affects transcription factor binding upstream of CD55 in the temporal cortex of a late-onset Alzheimer disease patient
- 2019
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 28:16, s. 2675-2685
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Familial cases suggest genetic components; however, monogenetic causes are few, and the vast majority of incidences have unknown cause. Sequencing efforts have focused on germline mutations, but improved technology has opened up for studies on somatic mutations in affected brain tissue samples. Here we use ultra-deep sequencing on brain and blood from early-onset AD (EOAD) and late-onset AD (LOAD) patients and non-AD individuals (n = 16). In total, 2.86 Mb of genomic regions, previously associated with AD, were targeted included 28 genes and upstream and downstream regulatory regions. Tailored downstream bioinformatics filtering identified 11 somatic single nucleotide variants in the temporal cortex in AD patients and none in the controls. One variant was validated to be present at 0.4% allele frequency in temporal cortex of a LOAD patient. This variant was predicted to affect transcription factor binding sites upstream of the CD55 gene, contributing to AD pathogenesis by affecting the complement system. Our results suggest that future studies targeting larger portions of the genome for somatic mutation analysis are important to obtain an increased understanding for the molecular basis of both EOAD and LOAD.
|
|
| 20. |
- Hendry, Alexandra, et al.
(författare)
-
Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
-
Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
-
Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
|
|
| 21. |
- Holl, Katsiaryna, et al.
(författare)
-
Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:12, s. 2923-2928
-
Tidskriftsartikel (refereegranskat)abstract
- According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs Were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG,). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers With high androstenedione levels had ail increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay or maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (C) 2009 UICC
|
|
| 22. |
- Holmberg, Jonas, 1976-, et al.
(författare)
-
Influence of Local Electropolishing Conditions on Ferritic–Pearlitic Steel on X-Ray Diffraction Residual Stress Profiling
- 2024
-
Ingår i: Journal of materials engineering and performance (Print). - : Springer. - 1059-9495 .- 1544-1024. ; 33, s. 3682-
-
Tidskriftsartikel (refereegranskat)abstract
- Layer removal with electropolishing is a well-established method when measuring residual stress profiles with lab-XRD. This is done to measure the depth impact from processes such as shot peening, heat treatment, or machining. Electropolishing is used to minimize the influence on the inherent residual stresses of the material during layer removal, performed successively in incremental steps to specific depths followed by measurement. Great control of the material removal is critical for the measured stresses at each depth. Therefore, the selection of size of the measurement spot and electropolishing parameters is essential. The main objective in this work is to investigate how different electrolytes and electropolishing equipment affect the resulting surface roughness, geometry, microstructure, and consequently the measured residual stress. A second objective has been to establish a methodology of assessing the acquired electropolished depth. The aim has been to get a better understanding of the influence of the layer removal method on the accuracy of the acquired depth. Evaluation has been done by electropolishing one ground and one shot peened sample of a low-alloy carbon steel, grade 1.1730, with different methods. The results showed a difference in stresses depending on the electrolyte used where the perchloric acid had better ability to retain the stresses compared to the saturated salt. Electropolishing with saturated salt is fast and results in evenly distributed material removal but has high surface roughness, which is due to a difference in electropolishing of the two phases, ferrite, and pearlite. Perchloric acid electropolishing is slower but generates a smooth surface as both ferrite and pearlite have the same material removal rates but may cause an increased material removal for the center of the electropolished area. In this work, it is suggested to use perchloric acid electropolishing for the final layer removal step. © 2023, The Author(s).
|
|
| 23. |
|
|
| 24. |
- Holmgren, Klas, et al.
(författare)
-
Preoperative biomarkers related to inflammation may identify high-risk anastomoses in colorectal cancer surgery : explorative study
- 2022
-
Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal anastomotic leakage can be considered a process of failed wound healing, for which related biomarkers might be a promising research area to decrease leak rates.METHODS: Patients who had elective surgery with a primary anastomosis for non-metastatic colorectal cancer, at two university hospitals between 1 January 2010 and 31 December 2015 were included. Patients with an anastomotic leak were identified and matched (1:1) to complication-free controls on the basis of sex, age, tumour stage, tumour location, and operating hospital. Preoperative blood samples were analysed by use of protein panels associated with systemic or enteric inflammation by proteomics, and enzyme-linked immunosorbent assays. Multivariable projection methods were used in the statistical analyses and adjusted for multiple comparisons to reduce false positivity. Rectal cancer tissue samples were evaluated with immunohistochemistry to determine local expression of biomarkers that differed significantly between cases and controls.RESULTS: Out of 726 patients undergoing resection, 41 patients with anastomotic leakage were matched to 41 controls. Patients with rectal cancer with leakage displayed significantly elevated serum levels of 15 proteins related to inflammation. After controlling for a false discovery rate, levels of C-X-C motif chemokine 6 (CXCL6) and C-C motif chemokine 11 (CCL11) remained significant. In patients with colonic cancer with leakage, levels of high-sensitivity C-reactive protein (hs-CRP) were increased before surgery. Local expression of CXCL6 and CCL11, and their receptors, were similar in rectal tissues between cases and controls.CONCLUSION: Patients with anastomotic leakage could have an upregulated inflammatory response before surgery, as expressed by elevated serological levels of CXCL6 and CCL11 for rectal cancer and hs-CRP levels in patients with colonic cancer respectively.
|
|
| 25. |
|
|
| 26. |
- Jumppanen, Mervi, et al.
(författare)
-
Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers
- 2007
-
Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Basal-phenotype or basal-like breast cancers are characterized by basal epithelium cytokeratin (CK5/14/17) expression, negative estrogen receptor ( ER) status and distinct gene expression signature. We studied the clinical and biological features of the basal-phenotype tumors determined by immunohistochemistry (IHC) and cDNA microarrays especially within the ER-negative subgroup. Methods IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers. The gene expression signature of the CK5/14 immunopositive tumors was investigated within a subset ( 100) of the breast tumors ( including 50 ER-negative tumors) with a cDNA microarray. Survival for basal-phenotype tumors as determined by CK5/14 IHC and gene expression signature was assessed. Results From the 375 analyzable tumor specimens, 48 (13%) were immunohistochemically positive for CK5/14. We found adverse distant disease-free survival for the CK5/14-positive tumors during the first years ( 3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01; 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04) but the significance was lost at the end of the follow-up period ( 10 years HR 1.43, 95% CI 0.84 to 2.43, p = 0.19). Gene expression profiles of immunohistochemically determined CK5/14-positive tumors within the ER-negative tumor group implicated 1,713 differently expressed genes ( p < 0.05). Hierarchical clustering analysis with the top 500 of these genes formed one basal-like and a non-basal-like cluster also within the ER-negative tumor entity. A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%). Both gene sets identified a basal-like cluster that included most of the CK5/14-positive tumors, but also immunohistochemically CK5/14-negative tumors. Within the ER-negative tumor entity there was no survival difference between the non-basal and basal-like tumors as identified by immunohistochemical or gene-expression-based classification. Conclusion Basal cytokeratin-positive tumors have a biologically distinct gene expression signature from other ER-negative tumors. Even if basal cytokeratin expression predicts early relapse among non-selected tumors, the clinical outcome of basal tumors is similar to non-basal ER-negative tumors. Immunohistochemically basal cytokeratin-positive tumors almost always belong to the basal-like gene expression profile, but this cluster also includes few basal cytokeratin-negative tumors.
|
|
| 27. |
- Kathol, Benno, et al.
(författare)
-
Description of regional geological and geophysical maps of the Skellefte District and surrounding areas
- 2005
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Beskrivningen ingår i serien Ba - översiktliga jordarts- och berggrundskartor. Syftet med denna beskrivning är att, utifrån SGUs berggrundskartering och geofysiska kartering i området, ge en så heltäckande bild av Skelleftefältets berggrund som möjligt. Tillsammans med norra Norrbotten och Bergslagen utgör Skelleftefältet ett av Sveriges viktigaste malmområden. Beskrivningen bygger på en genomgång och bearbetning av redan insamlad information samt kompletterande fältundersökningar.Beskrivningen innehåller dessutom en presentation av områdets geologiska utveckling, detaljerade geologiska beskrivningar för särskilt viktiga områden, förteckningar över de olika malmfyndigheterna, radiometriska data m.m.Till beskrivningen hör sex separata kartor: berggrundskarta (Ba 57:1), karta över metamorfosgrad, strukturer och isotopåldrar (Ba 57:2), karta över mineral- och bergartsresurser samt hydrotermalomvandlingar (Ba 57:3), magnetisk anomalikarta (Ba 57:4), Bougueranomalikarta (Ba 57:5), samt gammastrålningskarta, elektromagnetisk karta (VLF), Eulerträffar från tyngdkraftsdata och höjdreliefkarta (Ba 57:6).
|
|
| 28. |
- Li, Baojing, et al.
(författare)
-
Educational level and the risk of mental disorders, substance use disorders and self-harm in different age-groups : A cohort study covering 1,6 million subjects in the Stockholm region
- 2023
-
Ingår i: International Journal of Methods in Psychiatric Research. - : Wiley. - 1049-8931 .- 1557-0657. ; 32:4
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations between low education and risk of mental disorders, substance use disorders and self-harm in different age-groups.Methods: All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed-up for these disorders in health care registers 2001–2016. Subjects were stratified into four age-groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models.Results: Low education increased the risk of substance use disorders and self-harm in all age-groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism.Conclusion: Low education is associated with risk of most mental disorders, substance use disorders and self-harm in all age-groups, but especially among those aged 28–50 years.
|
|
| 29. |
- Li, M., et al.
(författare)
-
Model validation and uncertainty analysis in the wear prediction of a wet clutch
- 2016
-
Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 364-365, s. 112-121
-
Tidskriftsartikel (refereegranskat)abstract
- An uncertainty quantification analysis is performed to further investigate the nature of the “two-stage” wear process of the paper-based friction lining in a wet clutch. In this approach, the results of a computerized wear prediction model are examined through sensitivity analysis and a model validation that utilizes the Monte Carlo (MC) method. Extensive computational results that take into account the uncertainty and variability in the input data are presented to gain insight into the evolution of temperature and wear during the engagement process.
|
|
| 30. |
- Lindgren, Moa, et al.
(författare)
-
Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker
- 2022
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:14
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
|
|
| 31. |
- Lingesten, Niklas, et al.
(författare)
-
Apparatus for continuous wear measurements during wet clutch durability tests
- 2012
-
Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 288, s. 54-61
-
Tidskriftsartikel (refereegranskat)abstract
- Wet clutches are used in many applications today such as automatic transmissions and limited slip differentials in cars as well as in heavy duty equipment such as wheel loaders. The present study is concerned with the wear and engagement behavior of wet clutches in the latter type of application. A test rig is developed in which the wet clutch engagement is monitored during an arbitrary number of test cycles.This rig has many similarities with the SAE #2 test rig in that they are both inertia type test rigs. However, the test rig presented here has several original parts from heavy duty equipment in production incorporated into it. The data collection includes a continuous measurement of the position of the piston used to apply force on the clutch pack in addition to the separator disc temperatures, hydraulic actuating pressure and torque transfer characteristics. The measurements of the piston position can then be related to the clutch wear during a long test series.
|
|
| 32. |
- Lukanova, Annekatrin, et al.
(författare)
-
Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3 : a cross-sectional study in healthy women.
- 2004
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 150:2, s. 161-171
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.
|
|
| 33. |
- Lukanova, Annekatrin, et al.
(författare)
-
Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
- 2004
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:3, s. 425-432
-
Tidskriftsartikel (refereegranskat)abstract
- Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.
|
|
| 34. |
- Lukanova, Annekatrin, 1966-
(författare)
-
Endogenous hormones in the etiology of ovarian and endometrial cancers
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this thesis was to examine the relationship of pre-diagnostic circulating levels of sex-steroids (androgens and estrogens), sex hormone binding globuline (SHBG), insulin-like growth factor-I (IGF-I), IGF binding proteins (BP) and C-peptide (as a marker of pancreatic insulin secretion) with risk of ovarian and endometrial cancer. Additionally, the interrelationships of body mass index (BMI), sex-steroids, IGF-I and IGFBP-3 were examined. Two case-control studies were nested within 3 prospective cohort studies centered in New York (USA), Umeå (Sweden) and Milan (Italy). The ovarian study included 132 cancer cases. The endometrial study included 166 cancer cases in the IGF-I and C-peptide component and 124 postmenopausal cases in the sex-steroids component. For each case, two controls matching the case for cohort, age, menopausal status and date at recruitment were selected. In total 286 and 315 controls were included in the ovarian and endometrial cancer studies, respectively. Odds ratios (OR) and their 95% confidence intervals (CI) for cancer risk associated with increasing hormone concentrations were estimated by conditional logistic regression. The cross-sectional analysis was based on anthropometric and hormonal data from 620 controls selected for the two nested case-control studies. There was no association of prediagnostic androstenedione, testosterone, DHEAS, SHBG or estrone with ovarian cancer risk in the whole study population or in women who were pre- or postmenopausal at blood donation. In the premenopausal group, risk appeared to increase with increasing androstenedione (OR (95% CI) for the highest tertile: 2.35 (0.81-6.82), p=0.12). There was no association of IGF-I, IGFBP-1, 2, 3 or C-peptide concentrations with risk of ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at an early age (<55), circulating IGF-I was directly and strongly associated with risk (OR (95% CI): 4.74 (1.20-18.7), p<0.05 for the highest IGF-I tertile). In the endometrial study, previous observations were confimed that elevated circulating estrogens and androgens and decreased SHBG increase risk of developing endometrial malignancy after menopause. Multivariate ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels were: 4.13 (1.76-9.72), p<0.001 for estradiol; 3.67 (1.71-7.88), p=0.001 for estrone; 2.15 (1.05-4.40), p<0.04 for androstenedione; 1.74 (0.88-3.46), p=0.06 for testosterone; 2.90 (1.42-5.90), p<0.01 for DHEAS and 0.46 (0.20-1.05), p<0.01 for SHBG. Prediagnostic IGF-I, IGFBP-1, -2 and –3 were not related to risk of endometrial cancer in the whole study population. In postmenopausal women, levels of IGFBP-1 were inversely related to risk with an OR for the highest quartile of 0.36 (0.13-0.95), p<0.05. Endometrial cancer risk increased with increasing levels of C-peptide (p<0.01), up to an OR of 4.40 (1.65-11.7) for the highest quintile after adjustment for BMI and other confounders. The cross-sectional analyses showed that in both pre- and postmenopausal women SHBG decreased with increasing BMI. In the postmenopausal group, estrogens, testosterone and androstenedione increased with BMI, while the association with IGF-I was non-linear, the highest mean IGF-I concentration being observed in women with BMI between 24 and 25. In postmenopausal women, IGF-I was positively related to androgens, inversely correlated with SHBG, and was not correlated with estrogens. In conclusion, elevated pre-diagnostic sex-steroids, IGF-I or C-peptide increase risk of developing ovarian and endometrial cancer. BMI influences the circulating levels of these hormones, especially after menopause.
|
|
| 35. |
- Lukanova, Annekatrin, et al.
(författare)
-
Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden).
- 2002
-
Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 13:6, s. 509-516
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In this study we test the hypothesis of a nonlinear relationship of IGF-I with indices of body fat such as body mass index (BMI), insulin, and leptin.METHODS: The controls used in three case-control cancer studies nested in the Northern Sweden Health and Disease Cohort, were combined for this analysis. Measurements of plasma IGF-I, IGFBP-3, insulin, and leptin were available for 445 men and 391 women.RESULTS: In both men and women we found the highest mean IGF-I levels in subjects with BMI between 24 and 26. IGF-I concentrations decreased toward BMI < or = 20 and BMI > 30 in men; however, the results for women did not reach statistical significance. The molar ratio of IGF-I/IGFBP-3 showed a similar profile to that of IGF-I, although much less pronounced. The observed peak mean IGF-I levels in the second quintiles of insulin and leptin in men supported these findings. No significant variation of mean IGF-I levels across quintiles of insulin and leptin were observed in women.CONCLUSIONS: The results of this study provide evidence that IGF-I plasma concentrations vary substantially over a wide range of body weight and that the relationship is nonlinear.
|
|
| 36. |
- Lukanova, Annekatrin, et al.
(författare)
-
Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
- 2004
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:2, s. 262-268
-
Tidskriftsartikel (refereegranskat)abstract
- Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
|
|
| 37. |
- Lundin Kleberg, Johan, et al.
(författare)
-
Sex Differences in Social Attention in Infants at Risk for Autism
- 2019
-
Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 49:4, s. 1342-1351
-
Tidskriftsartikel (refereegranskat)abstract
- We studied visual attention to emotional faces in 10-month-old infant siblings of children with ASD (ASD-sibs; N = 70) and a siblings of typically developing children (N = 29) using static stimuli. Contrary to our predictions, we found no evidence for atypical gaze behavior in ASD-sibs when boys and girls were analyzed together. However, a sex difference was found in ASD-sibs' visual attention to the mouth. Male ASD-sibs looked more at the mouth across emotions compared to male controls and female ASD-sibs. In contrast, female ASD-sibs looked less at the mouth compared to female controls. These findings suggest that some aspects of early emerging atypical social attention in ASD-sibs may be sex specific.
|
|
| 38. |
- Lundin, Martin, 1975-, et al.
(författare)
-
Kåren och karriären : studentpolitiken som språngbräda
- 2016
-
Bok (refereegranskat)abstract
- I den här rapporten undersöker vi om arbetsmarknadsinträdet för studenter vid universitet och högskolor underlättas av att de deltar aktivt i studentkårspolitik. Vi studerar också om sannolikheten att ställa upp som kandidat i allmänna val ökar som en effekt av studentkårsengagemang. Data består av 5 000 kandidater till studentkårsfullmäktige vid universiteten i Uppsala, Lund och Stockholm mellan 1982 och 2005. Med hjälp av en "kvasi-experimentell" forskningsmetod visar vi att deltagande i kårfullmäktiges aktiviteter i hög grad påskyndar inträdet på arbetsmarknaden. Vi finner även att sannolikheten att på tre års sikt få ett välbetalt jobb ökar väsentligt. Däremot tycks alla arbetsmarknadseffekter vara kortlivade. Vidare visar analysen att sannolikheten att kandidera i allmänna val ökar av att väljas in i kårfullmäktige. De politiska effekterna tycks till skillnad från arbetsmarknadseffekterna vara stabila många år efter valet till studentkårsfullmäktige.
|
|
| 39. |
- Lundin, Martin, 1975-, et al.
(författare)
-
Leadership Experiences, Labor Market Entry, and Early Career Trajectories
- 2021
-
Ingår i: The Journal of human resources. - : University of Wisconsin Press. - 0022-166X .- 1548-8004. ; 56:2, s. 480-511
-
Tidskriftsartikel (refereegranskat)abstract
- Matching archive data on election discontinuities to register data on labor market trajectories, we estimate the causal effects of being elected into Swedish student union councils on subsequent labor market careers. Marginally elected students are much more likely to have a rapid transition into employment. Effects are not confined to establishments, organizations, or industries where previous candidates are employed, suggesting that the benefits are general in nature. Elected representatives have higher labor earnings within three years, but not thereafter. Overall, leadership experiences before labor market entry boost individuals' early careers, whereas mid-term outcomes are unaffected.
|
|
| 40. |
- Lundin, Martin, et al.
(författare)
-
Leadership Experiences within Civil Organizations and Candidacy in Public Elections : Causal Evidence from a Quasi-Experimental Approach
- 2016
-
Ingår i: Political Behavior. - : Springer Science and Business Media LLC. - 0190-9320 .- 1573-6687. ; 38:2, s. 433-454
-
Tidskriftsartikel (refereegranskat)abstract
- Standing as a candidate in public elections has been characterized as the ultimate act of political participation. We test the hypothesis that acquiring office within civil organizations increases the probability of becoming a candidate in public elections. In order to take self-selection problems into account, we provide quasi-experimental evidence using election discontinuities, in which we compare the likelihood of being nominated for public office between closely ranked winners and losers in Swedish student union (SU) elections. Our original data cover 5,000 SU candidates and register data on their candidacies in public elections (1991–2010). The analysis provides support to the hypothesis: Students elected to SU councils were about 34 percent (6 percentage points) more likely to become a candidate in a public election than SU council candidates who were not elected. The causal impact is fairly stable over time. The analysis makes important contributions to two interrelated bodies of literature: First, it provides political recruitment literature with causal evidence that acquiring leadership experiences at arenas outside of representative democratic institutions facilitate entry into election processes. Second, it provides strong evidence to an increasingly contested issue within political participation research by showing that certain organizational activities increase individuals’ political involvement.
|
|
| 41. |
- Lundin, Nannan, 1972-
(författare)
-
Impact of international competition on Swedish manufacturing : individual and firm-level evidence from the 1990s
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four papers examining the impact of international competition on Swedish manufacturing and labor market during the 1990s. By using detailed individual and firm-level information I aim to investigate how increased exposure to international trade, in terms of both export orientation and import penetration, affects technology development, profitability and wage structure. Paper [1] (co-authored with Pär Hansson) is a study on links between exporting behavior and productivity. We find support for the self-selection effect of firms, i.e. more productive firms are more likely to enter into the export market. In addition, we obtain evidence indicating that export enhances firm-level productivity. By recognizing the intra-industry heterogeneity in terms of exporting behavior and difference in productivity level among firms, we quantify both within-firm and reallocation effects that contribute to overall manufacturing productivity growth. The decomposition shows that the within-firm effect dominates, but intra-industry reallocation towards more productive firms has also taken place. A further breakdown of these two effects into domestic and export components shows that productivity growth appears to be more rapid for large exporting firms. Paper [2] analyzes the impact of import penetration on firm-level market power, measured by (average) price-cost margin. The total imports are divided into five country groups to investigate the differential strengths of the pro-competitive effects depending on the countries of origin. The EU-members and the EU-candidate countries (the recent EU members) are of special interest in the context of increased economic integration. The results indicate that imports from the EU-candidate countries have substantial disciplinary effects on firm-level market power, while imports from the EU-member countries only appear to have an impact in firms with large market shares in highly concentrated industries. Paper [3] examines how import competition from different origins and the presence of product differentiation affect market power of Swedish manufacturing firms during the 1990s. Applying Roeger’s method (1995), I perform the empirical analysis based on detailed firm-level data and estimate an average mark-up level of Swedish manufacturing firms. The general finding is that imports from both European countries and other high-income countries outside Europe impose disciplinary effects on price-cost margins of Swedish manufacturing firms. The strongest effect is from EU candidate countries (the recent EU members). However, the competitive pressure associated with import is relaxed in the presence of product differentiation. Paper [4] (co-authored with Lihong Yun) examines the inter-industry wage structure in Swedish manufacturing sectors using matched employer-employee data for the period 1996 to 2000. First, we use detailed individual and job characteristics to estimate industry-specific and time-varying wage premiums. Second, we examine the impact of international trade on the wage premiums, after controlling for effects of domestic competition and technical progress. Our results indicate that industries that face intensive import competition from low-income countries have lower wage premiums. Surprisingly, the wage premiums are not related to export intensities. Furthermore, technical progress, measured by investment in R&D activity, appears to enhance inter-industry wage premiums.
|
|
| 42. |
- Lundin, Pär
(författare)
-
Analysis of chromosomal rearrangements and gene copy number changes in breast cancer cells
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genome changes in terms of numerical chromosomal aberrations and structural rearrangements, including deletions, amplifications and translocations, gradually accumulate in the genome during tumor development. These genomic changes are likely to play an important role in the process of tumor progression. A detailed high resolution study of genome rearrangements in breast cancer and their relation to tumor progression and risk for metastasis was performed. A combination of the high resolution arrayCGH (aCGH) technique ROMA (Representational Oligonucleotide Microarray Analysis) and the molecular cytogenetic technique FISH (Fluorescence In Situ Hybridization) made it possible to identify genes and chromosomal regions that display aberrations as gains, losses and rearrangements. These chromosomal aberrations were analyzed quantitatively and related to the progression of the cancer disease. Three characteristic patterns of genomic copy number variations in breast cancer were identified, simplex, complex I (“sawtooth”) and complex II (“firestorm”). The simplex pattern has broad segments of duplication and deletion, usually comprising entire chromosomes or chromosome arms. The “sawtooth” pattern is characterized by many narrow segments of duplication and deletion, often alternating, more or less affecting all the chromosomes. The “firestorm” pattern resembles the simplex type except that the cancers contain at least one localized region of clustered, relatively narrow peaks of amplification, with each cluster limited to a single chromosome arm. The simplex pattern is associated with low malignant tumors whereas the complex patterns are associated with high malignant tumors. M-FISH enabled us to study the spatial organization between different chromosomal regions in the cell nucleus and validate the observed gene copy number changes quantitatively. A method, named Sector-Ploidy-Profiling (SPP), was developed and used to compare different subpopulations from different areas in a tumor. Clonal genomic heterogeneity was found to be very common in breast cancers. The clonal subpopulations were found to be either anatomically separated or intermixed. By comparing the different subpopulations, a better understanding of the order of genomic events during tumor development could be obtained. Inspired by the simplex and complex patterns we developed an objective estimate of genomic alterations in aCGH data. By using this method a clear relationship between genomic alterations (copy number changes and structural rearrangements) and gene expression subtypes was found. By combining ROMA with M-FISH it became possible to study specific translocations in interphase chromatin in clinical samples. The specific translocation between chromosome 1 and chromosome 16, t(1;16), could now be visualized in both invasive breast carcinoma and in ductal carcinoma in situ (DCIS), indicating that the translocation t(1;16) is an early event during breast cancer development. In DCIS however, cells with and without translocations were found to co-exist in the same area of the tumor. This suggests that intraductal proliferation leading to DCIS precedes the translocation t(1;16).
|
|
| 43. |
- Lundin, Per, 1971-
(författare)
-
Bilsamhället : Ideologi, expertis och regelskapande i efterkrigstidens Sverige
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the 1950s the number of cars in Sweden increased almost fivefold and the country attained the highest level of car ownership per capita in Europe. The rise and establishment of mass motoring was dramatically illustrated by the violent encounter between the car and the city. Despite the fact that congestion as well as road accidents were well-known, everyday occurrences, they reached previously unimagined heights through the growth of mass motoring. In this doctoral thesis Per Lundin focuses on the emergence of a group of planning experts as the key advocates of the idea of the “car society” as the solution to these problems. By fully adapting society to the car it would be possible to eliminate congestion and road accidents, thus affirming the continuing advance of the car. This ideal, which originated in the United States, became the goal and the dream of these experts.The general question addressed by Lundin is to what extent the actions and the ideologies of the experts interacted with the advent of mass motoring and the extensive urban building during the post-war period. In order to answer this question Lundin analyzes, firstly how the planning experts laid claim to the problems of congestion and road accidents, thereby restating them as exclusive planning problems, secondly how guidelines and standards for a car-conscious planning of cities and communities were developed based on the formulation of this problem and thirdly how, and to what extent, the guidelines and standards concerned were implemented in the town planning process.In the thesis Lundin argues that the dreams about a post-war Swedish society entirely adapted to the car by and large were realized. One important explanation of the fact that the physical adaptation of cities and societies to the car could proceed so quickly, on such a large scale and in similar forms all over the country, is found in the planning rules developed by the experts. The rules were the embodiment of the untroubled and unreflecting dreams nourished by the planning experts of the 1950s and the 1960s. Through the rules these ideological conceptions were reinforced and disseminated in a manner almost unable to stop. As the rules quickly were integrated with the planning instruments of administrative bodies locally, regionally and nationally, they set the tone for the extensive urban renewal of the following decades.
|
|
| 44. |
- Mason, James E., et al.
(författare)
-
A cross-sectional and longitudinal analysis of pre-diagnostic blood plasma biomarkers for early detection of pancreatic cancer
- 2022
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:21
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.
|
|
| 45. |
- Persson, Mikael J, 1980, et al.
(författare)
-
Does Deliberative Education Increase Civic Competence? : Results from a Field Experiment
- 2020
-
Ingår i: Journal of Experimental Political Science. - : Cambridge University Press. - 2052-2630 .- 2052-2649. ; 7:3, s. 199-208
-
Tidskriftsartikel (refereegranskat)abstract
- How should education be structured to most effectively increase civic outcomes such as political knowledge and democratic values? We present results from a field experiment in which we compare the effects of deliberative education and traditional teacher-centered education. The study is the largest field experiment on deliberative education to date and involved more than 1,200 students in 59 classrooms. We test the effects on four forms of civic competence: political knowledge, political interest, democratic values, and political discussion. In contrast to previous research, we find little evidence that deliberative education significantly increases civic competence.
|
|
| 46. |
|
|
| 47. |
- Wikman, Pär
(författare)
-
Kulturgeografin tar plats i välfärdsstaten : Vetenskapliga modeller och politiska reformer under efterkrigstidens första decennier
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study is to explain why human geography in Sweden became a planning science during the postwar period. Human geography had developed a sophisticated use of abstract models. The proliferation of models within in the social sciences was an international phenomenon during the postwar period. Actors within human geography in Sweden embraced this trend and strived towards making the constructions of models the methodological core of the discipline. Human geography, as an independent discipline, was being defined during this period. Simultaneously, human geography’s position within Swedish society was also being defined. This led a group of geographers, who were very much in favor of human geography as a science of models, to align themselves with the needs of the expanding welfare state.The group of actors, who reformed their discipline by making a specific form of geographical expertise essential to the welfare state, are referred to as geographers of planning. The most important actors within this group was, the not yet world famous, Torsten Hägerstrand and his colleague Sven Godlund. During the crucial years of the mid-1950s to the early-1960s, Hägerstrand held a position at Lund University while Godlund was engaged in a number of public investigations. Godlund regularly hired Hägerstran’s students and those same students used their experiences working for the public investigations to write their term papers. Through Godlund’s and Hägerstrand’s relationship a generations of human geographers was trained in planning practices and human geography was defined, within the public administration, by the works of Godlund and Hägerstrand.The most widely disseminated models were constructed from the German geographer Walter Christaller’s central place theory. By translating the general arguments of the theory into codified models, the theory was turned into a tool for planners. Thus the theoretical skills of human geographers where embedded in the practices of practical planning. This process turned the difference between research and planning into a difference of degree, rather than a difference of practice. During the municipal reforms of the 1960s the Swedish municipalities were remade to closer resemble the ideal of the central place theory. Through that reform the relationship between human geography and social planning was consolidated, making human geographers experts of planning. A labor market was created for geographers but it also placed an onus on the geographical institutions to supply the labor force for that market.
|
|
| 48. |
- Zeleniuch-Jacquotte, Anne, et al.
(författare)
-
Circulating enterolactone and risk of endometrial cancer
- 2006
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:10, s. 2376-2381
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.
|
|
