| 1. |
- Wadt, Karin A W, et al.
(författare)
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Molecular characterization of melanoma cases in denmark suspected of genetic predisposition.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Andersen, Steffen, et al.
(författare)
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Asset Integration and Attitudes to Risk : Theory and Evidence
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Measures of risk attitudes derived from experiments are often questioned because they are based on small stakes bets and do not account for the extent to which the decision-maker integrates the prizes of the experimental tasks with personal wealth. We exploit the existence of detailed information on individual wealth of experimental subjects in Denmark, and directly estimate risk attitudes and the degree of asset integration consistent with observed behavior. The behavior of the adult Danes in our experiment is consistent with partial asset integration: they behave as if some fraction of personal wealth is combined with experimental prizes in a utility function, and that this combination entails less than perfect substitution. Our subjects do not perfectly asset integrate. The implied risk attitudes from estimating these specifications imply risk premia and certainty equivalents that are a priori plausible under expected utility theory or rank dependent utility models. These are reassuring and constructive solutions to payoff calibration paradoxes. In addition, the rigorous, structural modeling of partial asset integration points to a rich array of neglected questions in risk management and policy evaluation in important field settings.
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| 4. |
- Andersen, Steffen, et al.
(författare)
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Asset Integration and Attitudes toward Risk : Theory and Evidence
- 2018
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Ingår i: Review of Economics and Statistics. - : MIT Press. - 0034-6535 .- 1530-9142. ; 100:5, s. 816-830
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Tidskriftsartikel (refereegranskat)abstract
- We provide evidence that choices over small stakes bets are consistent with assumptions of some payoff calibration paradoxes. We then exploit the existence of detailed information on individual wealth of our experimental subjects in Denmark, and directly estimate risk attitudes and the degree of asset integration. We discover that behavior is consistent with partial, rather than full, asset integration. The implied risk attitudes from estimating these specifications indicate risk premia and certainty equivalents that are a priori plausible. This theory and evidence suggest one constructive solution to payoff calibration paradoxes.
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| 5. |
- Andersen, Steffen, et al.
(författare)
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Multiattribute Utility Theory, Intertemporal Utility, and Correlation Aversion
- 2018
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Ingår i: International Economic Review. - : Wiley-Blackwell Publishing Inc.. - 0020-6598 .- 1468-2354. ; 59:2, s. 537-555
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Tidskriftsartikel (refereegranskat)abstract
- Convenient assumptions about qualitative properties of the intertemporal utility function have generated counterintuitive implications for the relationship between atemporal risk aversion and the intertemporal elasticity of substitution. If the intertemporal utility function is additively separable, then the latter two concepts are the inverse of each other. We review a theoretical specification with a long lineage in the literature on multi-attribute utility and use this theoretical structure to guide the design of a series of experiments that allow us to identify and estimate intertemporal correlation aversion. Our results show that subjects are correlation averse over lotteries with intertemporal income profiles.
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| 6. |
- Brockmann, Sarah J., et al.
(författare)
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CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 27:4, s. 706-715
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p. R15L and p. G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p. P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p. R15L and p. G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p. R15L, but not of CHCHD10 p. G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p. G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p. P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p. R15L and p. G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10.
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| 7. |
- Guidet, Bertrand, et al.
(författare)
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Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit
- 2018
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:7, s. 1027-1038
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU.METHODS: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up.RESULTS: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries.CONCLUSIONS: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country.TRIAL REGISTRATION: ClinicalTrials.gov (ID: NTC03134807).
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| 8. |
- Helferich, Anika M., et al.
(författare)
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Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS
- 2018
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 75:23, s. 4301-4319
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and functional studies suggest diverse pathways being affected in the neurodegenerative disease amyotrophic lateral sclerosis (ALS), while knowledge about converging disease mechanisms is rare. We detected a downregulation of microRNA-1825 in CNS and extra-CNS system organs of both sporadic (sALS) and familial ALS (fALS) patients. Combined transcriptomic and proteomic analysis revealed that reduced levels of microRNA-1825 caused a translational upregulation of tubulin-folding cofactor b (TBCB). Moreover, we found that excess TBCB led to depolymerization and degradation of tubulin alpha-4A (TUBA4A), which is encoded by a known ALS gene. Importantly, the increase in TBCB and reduction of TUBA4A protein was confirmed in brain cortex tissue of fALS and sALS patients, and led to motor axon defects in an in vivo model. Our discovery of a microRNA-1825/TBCB/TUBA4A pathway reveals a putative pathogenic cascade in both fALS and sALS extending the relevance of TUBA4A to a large proportion of ALS cases.
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| 9. |
- Hindelang, Steffen, et al.
(författare)
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The Day after : Alternatives to intra-EU BITs
- 2016
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Ingår i: Journal of World Investment & Trade. - : Brill. - 1660-7112 .- 2211-9000. ; 17:6, s. 984-1014
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Tidskriftsartikel (refereegranskat)abstract
- Intra-EU bilateral investment treaties (BITs) are the dinosaurs in the multi-level legal system of the European Union (EU). They sit uneasily with EU law, yet they provide an important tool for foreign investors to manage political risk in some EU Member States. This paper suggests, that alternatives to intra-EU BITs should best be developed from existing functional equivalents in EU law, ie substantive standards of protection in EU law should be made more transparent by the way of a ‘restatement’ of the pertinent legal practice. On principle, foreign investors should make use of functioning domestic courts. Where such institutions lack quality, the EU and the EU Member States should work towards their improvement. Meanwhile, a ‘safety net’ should be provided for foreign investors in case domestic courts fail to dispense justice. This ‘safety net’ may take the form of a PCA-administered arbitral forum or that of a ‘Unified Investment Court’.
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| 10. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 11. |
- Persson, Peter, et al.
(författare)
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Analysis of wind-induced vibrations in high-rise buildings
- 2016
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Ingår i: Proceedings of the INTER-NOISE 2016 - 45th International Congress and Exposition on Noise Control Engineering: Towards a Quieter Future. ; , s. 7650-7661
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Konferensbidrag (refereegranskat)abstract
- Buildings are getting taller due to increased urbanisation and densification of cities. More advanced construction methods and the desire to construct impressive buildings is also supporting the trend. Due to their inherent slenderness resulting in low eigenfrequencies, these buildings are susceptible to wind-induced vibrations which can be highly disturbing for occupants. Already barely perceivable acceleration levels within the low-frequency range relevant to whole-body vibrations can cause nausea and discomfort, while high acceleration levels can cause alarm and fear amongst the occupants. The paper summarises acceptable acceleration levels in high-rise buildings (here referred to as buildings over 200 m in height) stated in different building codes and previous work on the subject. Accelerations of a high-rise building subjected to wind-loads are evaluated using a full numerical model and one reduced with Ritz-vectors and the results are compared. The paper focusses on wind-load dynamics in early stages of the design process, with an intent to give an indication of the dynamic properties of a building.
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