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- Kalman, L. V., et al.
(författare)
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Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
- 2016
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
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Tidskriftsartikel (refereegranskat)abstract
- This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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- Dnyansagar, R., et al.
(författare)
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Dispersal and speciation: The cross Atlantic relationship of two parasitic cnidarians
- 2018
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903. ; 126, s. 346-355
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Tidskriftsartikel (refereegranskat)abstract
- How dispersal strategies impact the distribution of species and subsequent speciation events is a fundamental question in evolutionary biology. Sedentary benthic marine organisms, such as corals or sea anemones usually rely on motile larval stages for dispersal and therefore have a relatively restricted distribution along coasts. Edwardsiella lineata and Edwardsiella carnea are virtually indistinguishable edwardsiid sea anemones native to the east American and the Northern European coast, respectively. E. lineata is a facultative parasite to the ctenophore Mnemiopsis leidyi, while the life cycle of E. carnea is unknown. Recently M. leidyi was found in the Skagerrak carrying Edwardsiella sp. parasites, which raised the intriguing possibility that the invasive comb jellies acted as cargo for the facultative E. lineata parasites to establish a new population in Northern Europe. Here, we assessed the genetic differences between these two cryptic Edwardsiella species and isolated parasites from the invasive comb jelly M. leidyi in Sweden by comparing rRNA, whole transcriptomes, SNPs, ITS2 sequences and the gene complements of key developmental regulators, the Wnt gene family. We show that E. carnea and the parasite transcriptomes are more than 99% identical, hence demonstrating that E. carnea has a previously unknown parasitic life stage. ITS2 sequence analysis of E. carnea and E. lineata suggest that they may not be reproductively isolated. The transcriptomes of E. lineata and E. carnea are similar to 97% identical. We also estimate that the species diverged between 18.7 and 21.6 million years ago.
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- Ek, L., et al.
(författare)
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Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer : The RASTEN trial
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 29:2, s. 398-404
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients. Patients and methods: We carried out a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events. Results: In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of whom 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin [hazard ratio (HR), 1.11; 95% confidence interval (CI) 0.89-1.38; P=0.36 and HR, 1.18; 95% CI 0.95-1.46; P=0.14, respectively]. Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR, 0.31; 95% CI 0.11-0.84; P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms. Conclusion: LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWHassociated bleeding in cancer patients are warranted.
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- Ewart, L, et al.
(författare)
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Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery
- 2018
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Ingår i: Annual review of pharmacology and toxicology. - : Annual Reviews. - 1545-4304 .- 0362-1642. ; 58, s. 65-82
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.
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- Isaeva, Leyla, et al.
(författare)
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Amorphous W-S-N thin films: the atomic structure behind ultra-low friction
- 2015
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 82, s. 84-93
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Tidskriftsartikel (refereegranskat)abstract
- Amorphous W–S–N in the form of thin films has been identified experimentally as an ultra-low friction material, enabling easy sliding by the formation of a WS2 tribofilm. However, the atomic-level structure and bonding arrangements in amorphous W–S–N, which give such optimum conditions for WS2 formation and ultra-low friction, are not known. In this study, amorphous thin films with up to 37 at.% N are deposited, and experimental as well as state-of-the-art ab initio techniques are employed to reveal the complex structure of W–S–N at the atomic level. Excellent agreement between experimental and calculated coordination numbers and bond distances is demonstrated. Furthermore, the simulated structures are found to contain N bonded in molecular form, i.e. N2, which is experimentally confirmed by near edge X-ray absorption fine structure and X-ray photoelectron spectroscopy analysis. Such N2 units are located in cages in the material, where they are coordinated mainly by S atoms. Thus this ultra-low friction material is shown to be a complex amorphous network of W, S and N atoms, with easy access to W and S for continuous formation of WS2 in the contact region, and with the possibility of swift removal of excess nitrogen present as N2 molecules.
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- Johnsson, V, et al.
(författare)
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Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey
- 2021
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Ingår i: Fetal diagnosis and therapy. - : S. Karger AG. - 1421-9964 .- 1015-3837. ; 48:10, s. 720-737
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. <b><i>Methods:</i></b> We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. <b><i>Results:</i></b> Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. <b><i>Conclusion:</i></b> We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.
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