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Sökning: WFRF:(Wiklund F) > Lunds universitet

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1.
  • Jiang, X., et al. (författare)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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2.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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3.
  • Lango Allen, Hana, et al. (författare)
  • Hundreds of variants clustered in genomic loci and biological pathways affect human height.
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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5.
  • Bauer, Hjärtcentrum, et al. (författare)
  • Monitoring referral and treatment in soft tissue sarcoma : Study based on 1,851 patients from the Scandinavian Sarcoma Group Register
  • 2001
  • Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 72:2, s. 150-159
  • Tidskriftsartikel (refereegranskat)abstract
    • This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 1986-88 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.
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7.
  • Beutler, A., et al. (författare)
  • Adsorption properties of a mixed surface studied by high resolution core level photoemission : CO/0.5 ML Pd/Rh(111)
  • 1998
  • Ingår i: Surface Science. - 0039-6028. ; 411:1-2, s. 111-122
  • Tidskriftsartikel (refereegranskat)abstract
    • The coverage-dependent adsorption properties of a laterally heterogeneous bimetallic surface have been investigated by high resolution core level photoemission and low energy electron diffraction. The specific system under study was CO adsorbed on a Rh(111) surface onto which 2D Pd islands (coverage 0.5 ML) were formed by vapor deposition. The CO adsorption properties of the heterogeneous surface were compared with CO adsorption on a Rh(111) surface covered with a full Pd monolayer and with previous results for the CO/Rh(111) system. For low exposures CO is only found on the Rh(111) patches which can be explained by diffusion of CO from the Pd islands onto Rh parts in the adsorption process. At higher exposures CO diffusion from Rh to Pd is indicated. The origin of the diffusion processes can be found in the different coverage-dependent CO adsorption energies on the two surface parts.
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8.
  • Ekström, Magnus, et al. (författare)
  • Oral corticosteroid use, morbidity and mortality in asthma: A nationwide prospective cohort study in Sweden
  • 2019
  • Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:11, s. 2181-2190
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patterns and determinants of long-term oral corticosteroid (OCS) use in asthma and related morbidity and mortality are not well-described. In a nationwide asthma cohort in Sweden, we evaluated the patterns and determinants of OCS use and risks of OCS-related morbidities and mortality. Methods: Data for 217993 asthma patients (aged≥6years) in secondary care were identified between 2007 and 2014 using Swedish national health registries. OCS use at baseline was categorized: regular users (≥5mg/d/y; n=3299; 1.5%); periodic users (>0 but <5mg/d/y; n=49930; 22.9%); and nonusers (0mg/d/y; n=164765; 75.6%). Relative risks of becoming a regular OCS user and for morbidity and mortality were analysed using multivariable Cox regression. Results: At baseline, 24% of asthma patients had used OCS during the last year and 1.5% were regular users. Of those not using OCS at baseline, 26% collected at least one OCS prescription and 1.3% became regular OCS users for at least 1year during the median follow-up of 5.3years. Age at asthma diagnosis, increasing GINA severity and Charlson Comorbidity Index were associated with regular OCS use. Compared to periodic and non-OCS use, regular use was associated with increased incidence of OCS-related morbidities and greater all-cause mortality, adjusted HR 1.34 (95% CI 1.24-1.45). Conclusions: Oral corticosteroids use is frequent for asthma patients, and many are regular users. Regular OCS use is associated with increased risk of morbidity and mortality. These findings indicate that there is a need of other treatment options for patients with severe asthma who are using regular OCS. © 2019 The Authors Allergy Published by John Wiley & Sons Ltd
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9.
  • Ekström, Magnus, et al. (författare)
  • Risk of Rehospitalization and Death in Patients Hospitalized Due to Asthma
  • 2021
  • Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 9:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma is a heterogeneous inflammatory airway disease that continues to cause considerable morbidity across the world, with poor asthma control leading to hospitalizations. Objective: The present study investigated the risk of rehospitalization, mortality, and the management of patients with asthma who had been hospitalized because of an asthma exacerbation. Methods: National Swedish health registries were linked for patients 6 years or older who were admitted to hospital because of asthma (index date) between January 1, 2006, and December 31, 2015. Exacerbations were defined as asthma-related hospitalization, emergency visits, or collection of oral steroids. Patients were followed for rehospitalizations 12 months after the index date, health care resource utilization and treatment for 36 months, and mortality to study end. Regression models for time-to-event analyses were applied to assess risk factors for rehospitalization and mortality. Results: A total of 15,691 patients (mean age, 51.5 years; 63% females) were included, of whom 1,892 (12%) were rehospitalized for asthma within 12 months. Rehospitalized patients had a markedly increased risk of subsequent asthma-related mortality (adjusted hazard ratio, 2.80; 95% CI, 1.95-4.01) compared with those not rehospitalized. Two-third of the patients were not followed up by a hospital-based specialist, and 60% did not collect enough inhaled corticosteroid doses to cover daily treatment the year postindex. Conclusions: In this study, more than 1 in 10 patients were rehospitalized because of asthma within 12 months, and rehospitalizations were associated with asthma-related mortality. Few patients were seen by a hospital-based specialist, and few used inhaled corticosteroid continuously. Closer monitoring after hospitalization is needed. © 2020 The Authors
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10.
  • Juliusson, Gunnar, et al. (författare)
  • Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.
  • 2006
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:1, s. 42-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention ( RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region ( range 36-76%) and the two-year overall survival, with no censored observations (6-21%) ( v 2 for trend = 11.3, P < 0.001; r(2) = 0.86, P < 0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates ( P = 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.
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