| 1. |
- Zhang, YD, et al.
(författare)
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Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3353-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
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| 2. |
- Dam, J. S, et al.
(författare)
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Fiber-optic probe for noninvasive real-time determination of tissue optical properties at multiple wavelengths
- 2001
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Ingår i: Applied Optics. - 2155-3165. ; 40:7, s. 1155-1164
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Tidskriftsartikel (refereegranskat)abstract
- We present a compact, fast, and versatile fiber-optic probe system for real-time determination of tissue optical properties from spatially resolved continuous-wave diffuse reflectance measurements. The system collects one set of reflectance data from six source-detector distances at four arbitrary wavelengths with a maximum overall sampling rate of 100 Hz. Multivariate calibration techniques based on two-dimensional polynomial fitting are employed to extract and display the absorption and reduced scattering coefficients in real-time mode. The four wavelengths of the current configuration are 660, 785, 805, and 974 nm, respectively. Cross-validation tests on a 6 x 7 calibration matrix of Intralipid-dye phantoms showed that the mean prediction error at, e.g., 785 nm was 2.8% for the absorption coefficient and 1.3% for the reduced scattering coefficient. The errors are relative to the range of the optical properties of the phantoms at 785 nm, which were 0-0.3/cm for the absorption coefficient and 6-16/cm for the reduced scattering coefficient. Finally, we also present and discuss results from preliminary skin tissue measurements. (C) 2001 Optical Society of America
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| 3. |
- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 4. |
- JUUL, A, et al.
(författare)
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Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation
- 1995
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 80:8, s. 2534-2542
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Carnicelli, Anthony P., et al.
(författare)
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Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation
- 2021
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 107:9, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Aims The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug.Methods/Results We performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by <= 30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events <= 30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation.Conclusion Premature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.
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| 6. |
- Dalgaard, C. J., et al.
(författare)
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Roman roads to prosperity: Persistence and non-persistence of public infrastructure
- 2022
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Ingår i: Journal of Comparative Economics. - : Elsevier BV. - 0147-5967. ; 50:4, s. 896 - 916
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we explore the link between public transport infrastructure investments made during antiquity and the presence of infrastructure today; as well as the link between early infrastructure and economic activity, both in the past and in the present. We examine the territory under dominion of the Roman Empire at the zenith of its geographical extension (117 CE), and find a remarkable pattern of persistence showing that greater Roman road density goes along with (a) greater modern road density, (b) greater settlement formation in 500 CE, and (c) greater economic activity in 2010–2020. Exploiting a natural experiment, we find that persistence in road density and the strong link between early road density and contemporary economic development weaken to the point of insignificance in areas where the use of wheeled vehicles was abandoned and caravan trade routes replaced road-based trade from the first millennium CE until the late modern period. Studying channels of persistence, we identify the emergence of market towns during the early medieval period and the modern era as a robust mechanism sustaining the persistent effects of the Roman roads network. Our results contribute to a deeper understanding of the channels through which persistence in comparative development comes about.
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| 7. |
- Dam, J. S, et al.
(författare)
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Multiple polynomial regression method for determination of biomedical optical properties from integrating sphere measurements
- 2000
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Ingår i: Applied Optics. - 2155-3165. ; 39:7, s. 1202-1209
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Tidskriftsartikel (refereegranskat)abstract
- We present a new, to our knowledge, method for extracting optical properties from integrating sphere measurements on thin biological samples. The method is based on multivariate calibration techniques involving Monte Carlo simulations, multiple polynomial regression, and a Newton-Raphson algorithm for solving nonlinear equation systems. Prediction tests with simulated data showed that the mean relative prediction error of the absorption and the reduced scattering coefficients within typical biological ranges were less than 0.3%. Similar teats with data from integrating sphere measurements on 20 dye-polystyrene microsphere phantoms led to mean errors less than 1.7% between predicted and theoretically calculated values. Comparisons showed that our method was more robust and typically 5-10 times as fast and accurate as two other established methods, i.e., the inverse adding-doubling method and the Monte Carlo spline interpolation method. (C) 2000 Optical Society of America.
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| 8. |
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| 9. |
- Lundmark, Jöns, et al.
(författare)
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The effect of paroxetine on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients
- 1994
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 4:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the effect of the selective serotonin reuptake inhibiting drug (SSRI), paroxetine, on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients. 5-Hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured at baseline and after 3 weeks of treatment with 30 mg paroxetine daily. In line with similar studies on other SSRIs, influence on both the serotonin and noradrenaline metabolite was found. The mechanism behind the action of paroxetine on both 5-HIAA and MHPG is assumed to be an expression of the linkage between the serotonergic and noradrenergic systems in the brain. A frequently reported correlation between 5-HIAA and HVA was also found. The analysis of paroxetine in CSF proves the transportation of the drug into the central nervous system.
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| 10. |
- Olafsdottir, G., et al.
(författare)
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Methods to evaluate fish freshness in research and industry
- 1997
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Ingår i: Trends in Food Science & Technology. - 0924-2244 .- 1879-3053. ; 8:8, s. 258-265
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of the various descriptors of properties that are encountered in fish immediately after harvest or catch must be known as well as of the changes in properties that take place over time. This information can be gained by performing controlled storage experiments that extend from the time of harvest until spoilage. Freshness, loss of freshness and spoilage can thus be monitored; once the dynamics and the rate of the various changes that occur have been measured, the next step is to try to develop a model. The future aim is to use a model to determine when a sample was harvested or predict the remaining shelf life of an unknown sample. To achieve this aim, it is useful to combine several measurements obtained by different methodologies and correlate the findings with sensory assessments, which are currently the most used method to evaluate fish freshness.
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