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Sökning: WFRF:(Palsdottir K)

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  • Fages, A., et al. (författare)
  • Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
  • 2019
  • Ingår i: Cell. - 0092-8674. ; 177:6, s. 1419-
  • Tidskriftsartikel (refereegranskat)abstract
    • Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
  • Falconer, Henrik, et al. (författare)
  • Robot-assisted approach to cervical cancer (RACC) : An international multi-center, open-label randomized controlled trial
  • 2019
  • Ingår i: International Journal of Gynecological Cancer. - : Wiley-Blackwell. - 1048-891X .- 1525-1438. ; 29:6, s. 1072-1076
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. Trial Registration The trial is registered at ClinicalTrials.gov (NCT03719547).
  • Helgadottir, Anna, et al. (författare)
  • The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
  • 2008
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718. ; 40:2, s. 217-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
  • Spjuth, Ola, 1977-, et al. (författare)
  • E-Science technologies in a workflow for personalized medicine using cancer screening as a case study
  • 2017
  • Ingår i: JAMIA Journal of the American Medical Informatics Association. - : Oxford University Press. - 1067-5027 .- 1527-974X. ; 24:5, s. 950-957
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We provide an e-Science perspective on the workflow from risk factor discovery and classification of disease to evaluation of personalized intervention programs. As case studies, we use personalized prostate and breast cancer screenings.Materials and Methods: We describe an e-Science initiative in Sweden, e-Science for Cancer Prevention and Control (eCPC), which supports biomarker discovery and offers decision support for personalized intervention strategies. The generic eCPC contribution is a workflow with 4 nodes applied iteratively, and the concept of e-Science signifies systematic use of tools from the mathematical, statistical, data, and computer sciences.Results: The eCPC workflow is illustrated through 2 case studies. For prostate cancer, an in-house personalized screening tool, the Stockholm-3 model (S3M), is presented as an alternative to prostate-specific antigen testing alone. S3M is evaluated in a trial setting and plans for rollout in the population are discussed. For breast cancer, new biomarkers based on breast density and molecular profiles are developed and the US multicenter Women Informed to Screen Depending on Measures (WISDOM) trial is referred to for evaluation. While current eCPC data management uses a traditional data warehouse model, we discuss eCPC-developed features of a coherent data integration platform.Discussion and Conclusion: E-Science tools are a key part of an evidence-based process for personalized medicine. This paper provides a structured workflow from data and models to evaluation of new personalized intervention strategies. The importance of multidisciplinary collaboration is emphasized. Importantly, the generic concepts of the suggested eCPC workflow are transferrable to other disease domains, although each disease will require tailored solutions.
  • Anveden, Åsa, et al. (författare)
  • ITIH-5 Expression in Human Adipose Tissue Is Increased in Obesity.
  • 2012
  • Ingår i: Obesity. - 1930-7381. ; 20:4, s. 708-714
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipocytes secrete many proteins that regulate metabolic functions. The gene inter-α (globulin) inhibitor H5 (ITIH-5) encodes a secreted protein and is known to be expressed abundantly in the placenta. However, using gene expression profiles data we observed high expression of ITIH-5 in adipose tissue. The aim of this study was to test the hypothesis that ITIH-5 is strongly expressed in human adipocytes and adipose tissue, and is related to obesity and clinical metabolic variables. ITIH-5 adipose tissue mRNA expression was analyzed with DNA microarray and real-time PCR, and its association with clinical variables was examined. ITIH-5 protein expression was analyzed using western blot. ITIH-5 mRNA expression was abundant in human adipose tissue, adipocytes, and placenta, and higher in subcutaneous (sc) compared to omental adipose tissue (P < 0.0001). ITIH-5 mRNA and protein expression in sc adipose tissue were higher in obese compared to lean subjects (P < 0.0001 and P < 0.001, respectively). ITIH-5 mRNA expression was reduced after diet-induced weight loss (P < 0.0001). ITIH-5 mRNA expression was associated with anthropometry and clinical metabolic variables. In conclusion, ITIH-5 is highly expressed in sc adipose tissue, increased in obesity, down regulated after weight loss, and associated with measures of body size and metabolism. Together, this indicates that ITIH-5 merits further investigation as a regulator of human metabolism.
  • Jansson, John-Olov, 1954, et al. (författare)
  • Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 115:2, s. 427-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
  • Pálsdóttir, K, et al. (författare)
  • Inter-observer agreement of transvaginal ultrasound and magnetic resonance imaging in local staging of cervical cancer.
  • 2021
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - 0960-7692 .- 1469-0705.
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To evaluate the inter-observer agreement in relation to observer experience for the assessment of local tumor extension in women with cervical cancer, using transvaginal ultrasound (US) and magnetic resonance imaging (MRI).METHODS: The observers comprised six US specialists with, and seven without previous experience of cervical cancer assessment, five experienced radiologists in pelvic MRI, and four less experienced radiology residents without previous MRI experience. The less experienced US observers, and all MRI observers underwent comprehensive training on assessment of cervical tumor extension while experienced US observers received written directives. All observers were assigned the same images from cervical cancer patients of all stages (n=60) for off-line evaluation on tumor detection, cervical stromal- (>1/3), and parametrial invasion. Inter-observer agreement was measured using Fleiss kappa, with 95% CI.RESULTS: Experienced and less experienced US observers had moderate agreement regarding tumor detection Fleiss κ [95% CI] (0.46 [0.40-0.53], and 0.46 [0.41-0.52]), stromal invasion (0.45 [0.38-0.51] and 0.53 [0.40-0.58]) and parametrial invasion (0.57 [0.51-0.64], and 0.44 [0.39-0.50]), respectively. Experienced and less experienced MRI observers had good κ [95% CI] (0.70 [0.62-0.78]) and moderate agreement (0.51 [0.41-0.62]), regarding tumor detection, good agreement regarding stromal invasion (0.80 [0.72-0.88] and 0.71 [0.61-0.81]) and parametrial invasion (0.69 [0.61-0.77] and 0.71[0.61-0.81]), respectively.CONCLUSION: The inter-observer agreement was moderate for US, and moderate - good for MRI regarding the assessment of local tumor extension. The level of inter-observer agreement was only associated with experience among US observers regarding parametrial invasion. This article is protected by copyright. All rights reserved.
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  • [1]23Nästa

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