| 1. |
- Breznau, Nate, et al.
(författare)
-
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
|
|
| 2. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 3. |
- Bjugård Nyberg, Henrik, et al.
(författare)
-
Saddle-Reset for Robust Parameter Estimation and Identifiability Analysis of Nonlinear Mixed Effects Models
- 2020
-
Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 22:4
-
Tidskriftsartikel (refereegranskat)abstract
- Parameter estimation of a nonlinear model based on maximizing the likelihood using gradient-based numerical optimization methods can often fail due to premature termination of the optimization algorithm. One reason for such failure is that these numerical optimization methods cannot distinguish between the minimum, maximum, and a saddle point; hence, the parameters found by these optimization algorithms can possibly be in any of these three stationary points on the likelihood surface. We have found that for maximization of the likelihood for nonlinear mixed effects models used in pharmaceutical development, the optimization algorithm Broyden-Fletcher-Goldfarb-Shanno (BFGS) often terminates in saddle points, and we propose an algorithm, saddle-reset, to avoid the termination at saddle points, based on the second partial derivative test. In this algorithm, we use the approximated Hessian matrix at the point where BFGS terminates, perturb the point in the direction of the eigenvector associated with the lowest eigenvalue, and restart the BFGS algorithm. We have implemented this algorithm in industry standard software for nonlinear mixed effects modeling (NONMEM, version 7.4 and up) and showed that it can be used to avoid termination of parameter estimation at saddle points, as well as unveil practical parameter non-identifiability. We demonstrate this using four published pharmacometric models and two models specifically designed to be practically non-identifiable.
|
|
| 4. |
- de Girolamo, Giovanni, et al.
(författare)
-
Medical comorbidities in bipolar disorder (BIPCOM) : clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol.
- 2024
-
Ingår i: International journal of bipolar disorders. - : Springer. - 2194-7511. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities.METHODS: The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology.DISCUSSION: BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases.TRIAL REGISTRATION: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.
|
|
| 5. |
|
|
| 6. |
- Hanssen-Bauer, O. W., et al.
(författare)
-
Comparison of three DWM-based wake models at above-rated wind speeds
- 2023
-
Ingår i: WAKE CONFERENCE 2023. - : Institute of Physics Publishing (IOPP).
-
Konferensbidrag (refereegranskat)abstract
- In this study we investigate three mid-fidelity wind turbine wake models based on the dynamic wake meandering (DWM) model principle, and compare their performance with a reference dataset, produced with large-eddy simulations using the actuator line model. The models are compared with respect to flow field, power, and loads on a row of four 5MW reference turbines experiencing above-rated wind conditions. In general, the DWM models show fairly good agreement with large-eddy simulation for the time-averaged flow fields, blade forces and power, with increasing differences along the turbine row. Also when comparing fatigue loads of blade root moments, the differences between the models increase further into the row, with deviations up to 25 % of the reference case. However, while the development in blade root moment fatigue along the turbine row is predominantly driven by the energy content at the frequency corresponding to the turbine's rotational period (1P) for the DWM models, the large-eddy simulation results suggest that the key drivers for the blade root and tower loads are the increase in meandering and energy at higher frequencies (> 1P) deeper into the turbine row. For the tower loads, the DWM models highly underestimate the fatigue for the waked turbines. From these results, we suggest priorities for future model developments so that robust model implementations can be used in wind farm design and operation.
|
|
| 7. |
- Hanssen-Bauer, O. W., et al.
(författare)
-
Dependence of wind turbine loads on inlet flow field
- 2020
-
Ingår i: Science of making torque from wind (TORQUE 2020), pts 1-5. - : IOP Publishing.
-
Konferensbidrag (refereegranskat)abstract
- In wind farm simulations, the inflow wind field plays a crucial role in the accuracy of both power production, structural load predictions and the turbulent wake development behind wind turbines. Three different inflow wind field generation techniques, namely the Mann model, a reduced order based model described herein and LES data, are used in this study to characterise the relation between the inflow and the structural response of the wind turbine. In addition, the wake development under different inflow conditions are studied. The turbulence statistics of the reduced-order model and the LES data are similar to each other while the Mann turbulence has different turbulence profiles and spectral characteristics. An in-house developed aeroelastic code, 3Dfloat, is used for structural response analysis. The differences between the inflow fields are mainly attributed to the turbulence intensity profiles, and differences in their spectral characteristics.
|
|
| 8. |
- Hansson, Oskar, et al.
(författare)
-
Pre-analytical protocol for measuring Alzheimer's disease biomarkers in fresh CSF
- 2020
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to establish a standardized, routine-use pre-analytical protocol for measuring Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). Methods: The effect of pre-analytical factors (sample collection/handling/storage/transportation) on biomarker levels was assessed using freshly collected CSF. Tube type/sterilization was assessed using previously frozen samples. A low-bind false-bottom tube (FBT, Sarstedt) was used for all experiments, except tube types/sterilization experiments. Biomarkers were measured using Elecsys CSF assays. Results: Amyloid beta (Aβ)1-42 levels varied by tube type, using a low-bind FBT reduced variation. Aβ1-42 levels were higher with no mixing versus roller/inversion mixing. Aβ1-42 levels were lower with horizontal versus upright transportation; this was resolved by maximal tube filling and storage at 2°C to 8°C. Aβ1-40 levels were less strongly affected. Phospho-tau and total-tau levels were largely unaffected. Discussion: We propose an easy-to-use, standardized, routine-use pre-analytical protocol, using low-bind FBTs, for measuring AD CSF biomarkers in clinical practice.
|
|
| 9. |
- Köster, Jan, et al.
(författare)
-
Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development
- 2020
-
Ingår i: Cancer Genetics. - : ELSEVIER SCIENCE INC. - 2210-7762 .- 2210-7770. ; 241, s. 34-41
-
Tidskriftsartikel (refereegranskat)abstract
- The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.
|
|
| 10. |
|
|
