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- Schmoll, H. J., et al.
(författare)
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ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:10, s. 2479-2516
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.
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- Jagannathan, Vidhya, et al.
(författare)
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A Mutation in the SUV39H2 Gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) Provides Insights into the Epigenetics of Keratinocyte Differentiation
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:10, s. e1003848-
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4x10(-14)). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38x coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.
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- Kaminski, M. F., et al.
(författare)
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The NordICC Study : Rationale and design of a randomized trial on colonoscopy screening for colorectal cancer
- 2012
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 44:7, s. 695-702
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aim: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. Study design: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. Power analysis: We hypothesize a 50% CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50% compliance, yielding a 25% mortality reduction among those invited to screening. For 90% power and a two-sided alpha level of 0.05, using a 2: 1 randomization, 45600 individuals will be randomized to control, and 22800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. Conclusions: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.
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- Nevens, Frederik, et al.
(författare)
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A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 375:7, s. 631-43
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Tidskriftsartikel (refereegranskat)abstract
- Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.
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- Almquist, Martin, et al.
(författare)
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A prospective study on an innovative online forum for peer reviewing of surgical science
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Peer review is important to the scientific process. However, the present system has been criticised and accused of bias, lack of transparency, failure to detect significant breakthrough and error. At the British Journal of Surgery (BJS), after surveying authors' and reviewers' opinions on peer review, we piloted an open online forum with the aim of improving the peer review process. Methods In December 2014, a web-based survey assessing attitudes towards open online review was sent to reviewers with a BJS account in Scholar One. From April to June 2015, authors were invited to allow their manuscripts to undergo online peer review in addition to the standard peer review process. The quality of each review was evaluated by editors and editorial assistants using a validated instrument based on a Likert scale. Results The survey was sent to 6635 reviewers. In all, 1454 (21.9%) responded. Support for online peer review was strong, with only 10% stating that they would not subject their manuscripts to online peer review. The most prevalent concern was about intellectual property, being highlighted in 118 of 284 comments (41.5%). Out of 265 eligible manuscripts, 110 were included in the online peer review trial. Around 7000 potential reviewers were invited to review each manuscript. In all, 44 of 110 manuscripts (40%) received 100 reviews from 59 reviewers, alongside 115 conventional reviews. The quality of the open forum reviews was lower than for conventional reviews (2.13 (± 0.75) versus 2.84 (± 0.71), P<0.001). Conclusion Open online peer review is feasible in this setting, but it attracts few reviews, of lower quality than conventional peer reviews.
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