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- Aad, G., et al.
(författare)
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- 2013
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :11
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :6
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Adamina, Michel, et al.
(författare)
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ECCO Topical Review Optimising Reporting in Surgery, Endoscopy, and Histopathology Collaboration Between S-ECCO, EduCom, H-ECCO
- 2021
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 15:7, s. 1089-1105
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Forskningsöversikt (refereegranskat)abstract
- Background and Aims: Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach.The quality of medical reporting is crucial in this context.The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. Methods: A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohns and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when >= 80% of participants agreed on a recommendation. Results: Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. Conclusions: Interdisciplinary high-quality care requires thorough and standardised reporting across specialties.This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.
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| 4. |
- Coral, Daniel
(författare)
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Characterisation of the genetic discordance between body mass index and type 2 diabetes: a phenome-wide analysis : No 111
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 63
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Konferensbidrag (refereegranskat)abstract
- Background and aims: Obesity is on the rise globally, and is a leading risk factor for T2D. However, it is very heterogeneous, with varying degrees of T2D risk within the same levels of BMI. Better classification may lead to improve outcomes of current preventive and therapeutic strategies. Moreover, by elucidating the mechanisms uncoupling obesity from T2D risk, new possible therapeutic targets may emerge. Leveraging the vast amount of genetic data produced to date may contribute to reach these goals while overcoming the obstacles imposed by common assumptions, biases and confounders present in observational studies. Our aim is to compare the phenome-wide association patterns of BMI-increasing genetic profiles that either concordantly increase or discordantly decrease T2D risk. Materials and methods: Highly concordant and highly discordant SNPs between BMI and T2D were obtained from the latest GWAS for both conditions. Their standardized effect sizes (SES) across multiple traits in the phenome, metabolome, proteinome and transcriptome were retrieved from the online genomic repositories. After alignment to the BMI-increasing allele, these effects were organized into a SNP x Trait matrix. A hierarchical clustering technique, combining PCA and Random Forest algorithms was applied, retrieving the optimal number of clusters of traits, organized in order of importance, useful to distinguish a discordant from a concordant SNP. Posterior probabilities of colocalization with T2D were calculated for each gene using transcriptome results. Tissue, biological process, molecular mechanism and cellular component enrichments were evaluated. The predictive potential of GRSs informed by these findings were assessed in the UK Biobank dataset. Results: 121 SNPs were found to be significantly associated with BMI and T2D. 18 were discordant and 104 concordant. A total of 1372 variables were included in the analyses (Phenome = 546, Metabolome = 233, Proteinome = 593). The most important difference between discordant and concordant SNPs in the phenome matrix was found in a cluster of traits led by hypertension (Mean discordant SES = -1.59, Mean concordant SES = 2.56), highly correlated with two clusters led by coronary heart disease and overall health status, respectively. The second most important cluster was led by physical activity-adjusted WHR (Mean discordant SES = -2.69, Mean concordant SES = 0.24). The model obtained from the phenome matrix had the highest classification performance (Matthews Correlation Coefficient, MCC = 0.79). Metabolome results showed differences in polyunsaturated fatty acids and lipid contents in VLDL, but with lower performance (MCC = 0.67). The model from the proteinome matrix was unable to correctly classify SNPs (MCC = -0.03). Two genes (CCDC92 and DNAH10) showed the strongest association within the discordant set in adipose tissue, both involved in cilia formation. A GRS of these 121 SNPs with weights derived from the clusters with high classification performance was highly associated with T2D in both the general and obese populations in UK Biobank (p < 1x1016). Conclusion: The main difference between BMI-increasing genetic profiles that either discordantly decrease or concordantly increase T2D risk is found in hypertension risk and physical activity-adjusted WHR. These traits can be used to inform GRSs to better classify T2D risk in obesity. Molecular mechanisms behind the discordant profile appear to involve cilia formation in the adipose tissue.
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| 5. |
- Hovstadius, Peter, et al.
(författare)
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A Phase I Study of CHS 828 in Patients with Solid Tumor Malignancy
- 2002
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 8:9, s. 2843-2850
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Tidskriftsartikel (refereegranskat)abstract
- CHS 828 is a cyanoguanidine, which has demonstrated potent antitumor activity in preclinical tumor models. The activity of CHS 828 in vitro showed only low to moderate correlation to other antineoplastic agents suggesting a unique mechanism of action. Ten females and 6 males (median age 58 years) with solid tumors refractory to standard therapy were included in this Phase I study. The study drug was administered to fasting patients as a single oral dose on days 1–5 of each treatment cycle. Patients received one to six cycles of treatment. The doses ranged from 30 mg to 200 mg (total dose within a cycle). Hematological toxicity was generally mild and dominated by transient thrombocytopenia and lymphocytopenia. Nonhematological toxicity most frequently consisted of nausea, vomiting, diarrhea, fatigue, and localized genital mucositis. The dose-limiting toxicities were thrombocytopenia, thrombosis, esophagitis, diarrhea, and constipation. The recommended Phase II dose of CHS 828 was 20 mg once daily for 5 days in cycles of 28 days duration. The extent of systemic exposure of CHS 828 across patients was approximately dose proportional. The time at which the highest drug concentration occurs was 2.2 ± 1.3 h and half-life was 2.1 ± 0.52 h (mean ± SD). Large intra- and interindividual variation in dose level-adjusted maximum plasma concentration and the area under the curve from time 0 h to infinity were observed. There was an apparent inverse relationship between systemic exposure of CHS 828, and thrombocyte and lymphocyte nadir levels. No objective tumor responses were observed, and 7 patients showed stable disease after two courses of therapy.
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| 9. |
- Lippe, Melvin, et al.
(författare)
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Using agent-based modelling to simulate social-ecological systems across scales
- 2019
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Ingår i: Geoinformatica. - : Springer Science and Business Media LLC. - 1384-6175 .- 1573-7624. ; 23:2, s. 269-298
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Tidskriftsartikel (refereegranskat)abstract
- Agent-based modelling (ABM) simulates Social-Ecological-Systems (SESs) based on the decision-making and actions of individual actors or actor groups, their interactions with each other, and with ecosystems. Many ABM studies have focused at the scale of villages, rural landscapes, towns or cities. When considering a geographical, spatially-explicit domain, current ABM architecture is generally not easily translatable to a regional or global context, nor does it acknowledge SESs interactions across scales sufficiently; the model extent is usually determined by pragmatic considerations, which may well cut across dynamical boundaries. With a few exceptions, the internal structure of governments is not included when representing them as agents. This is partly due to the lack of theory about how to represent such as actors, and because they are not static over the time-scales typical for social changes to have significant effects. Moreover, the relevant scale of analysis is often not known a priori, being dynamically determined, and may itself vary with time and circumstances. There is a need for ABM to cross the gap between micro-scale actors and larger-scale environmental, infrastructural and political systems in a way that allows realistic spatial and temporal phenomena to emerge; this is vital for models to be useful for policy analysis in an era when global crises can be triggered by small numbers of micro-level actors. We aim with this thought-piece to suggest conceptual avenues for implementing ABM to simulate SESs across scales, and for using big data from social surveys, remote sensing or other sources for this purpose.
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| 11. |
- Sonnenschein, Jonas, et al.
(författare)
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Minimum energy performance standards for the 1.5 °C target: an effective complement to carbon pricing
- 2019
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Ingår i: Energy Efficiency. - : Springer Science and Business Media LLC. - 1570-646X .- 1570-6478. ; 12:2, s. 387-402
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Tidskriftsartikel (refereegranskat)abstract
- Radical energy efficiency improvements are needed to keep global warming within 1.5 °C until the end of the century. Minimum energy performance standards (MEPS) are a widely applied policy instrument to improve the energy efficiency of appliances and reduce CO2 emissions, but they are criticized as redundant if an overarching carbon pricing scheme is in place. In order to better understand how MEPS could play a more effective role in reaching the 1.5 °C target, life cycle costs (LCC) for four home appliances were modelled considering a cost for emitting CO2. First, a significant social cost of carbon was introduced in a LCC optimisation model and it was found that a modest tightening of MEPS is sufficient to account for the climate externality. Second, more stringent MEPS were modelled and it was found that the switching prices needed to incentivize a shift up one or two efficiency classes were far higher than current carbon prices. These results have several implications for climate policy towards the 1.5 °C target. MEPS can easily internalize the climate externality and have the advantage over carbon pricing that policy makers can be certain that consumers actually move to more efficient appliances. While stringent MEPS do not appear to be economically efficient on the short-run, they are likely cost-effective in long-run 1.5 °C-consistent scenarios.
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