| 1. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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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
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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.
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| 2. |
- White, Helen E., et al.
(författare)
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Standardization of molecular monitoring of CML : results and recommendations from the European treatment and outcome study
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:7, s. 1834-1842
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Tidskriftsartikel (refereegranskat)abstract
- Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1(IS) and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
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| 3. |
- Zimyanin, Vitaly L., et al.
(författare)
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Live cell imaging of ATP levels reveals metabolic compartmentalization within motoneurons and early metabolic changes in FUS ALS motoneurons
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Motoneurons are one of the most energy-demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultrastructure, transport, and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and the proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression is not fully understood yet. Here, we utilize hiPCS-derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in fused in sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons are accompanied by an overall upregulation of mitochondrial components and a significant increase in metabolic rates that correspond to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of diseased motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments, with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts the metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms.
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| 4. |
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| 5. |
- Abele, H., et al.
(författare)
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Particle physics at the European Spallation Source
- 2023
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Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
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Forskningsöversikt (refereegranskat)abstract
- Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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| 6. |
- Alshammari, Hatem, et al.
(författare)
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Antimicrobial Properties of Strontium Functionalized Titanium Surfaces for Oral Applications, A Systematic Review
- 2021
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Ingår i: Coatings. - : MDPI. - 2079-6412. ; 11:7
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Forskningsöversikt (refereegranskat)abstract
- The aim of this systematic review was to assess the current scientific evidence of the antimicrobial potential of strontium (Sr) when used to functionalize titanium (Ti) for oral applications. Out of an initial list of 1081 potentially relevant publications identified in three electronic databases (MEDLINE via PubMed, Scopus, and Cochrane) up to 1 February 2021, nine publications based on in vitro studies met the inclusion criteria. The antimicrobial potential of Sr was investigated on different types of functionalized Ti substrates, employing different application methods. Nine studies reported on the early, i.e., 6-24 h, and two studies on the late, i.e., 7-28 days, antimicrobial effect of Sr, primarily against Staphylococcus aureus (S. aureus) and/or Escherichia coli (E. coli). Sr-modified samples demonstrated relevant early antimicrobial potential against S. aureus in three studies; only one of which presented statistical significance values, while the other two presented only the percentage of antimicrobial rate and biofilm inhibition. A relevant late biofilm inhibition potential against S. aureus of 40% and 10%-after 7 and 14 days, respectively-was reported in one study. Combining Sr with other metal ions, i.e., silver (Ag), zinc (Zn), and fluorine (F), demonstrated a significant antimicrobial effect and biofilm inhibition against both S. aureus and E. coli. Sr ion release within the first 24 h was generally low, i.e., below 50 mu g/L and 0.6 ppm; however, sustained Sr ion release for up to 30 days, while maintaining up to 90% of its original content, was also demonstrated. Thus, in most studies included herein, Sr-functionalized Ti showed a limited immediate (i.e., 24 h) antimicrobial effect, likely due to a low Sr ion release; however, with an adequate Sr ion release, a relevant antimicrobial effect, as well as a biofilm inhibition potential against S. aureus-but not E. coli-was observed at both early and late timepoints. Future studies should assess the antimicrobial potential of Ti functionalized with Sr against multispecies biofilms associated with peri-implantitis.
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| 7. |
- Andersen, Jeppe R., et al.
(författare)
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A Positive Resampler for Monte Carlo events with negative weights
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:11
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Tidskriftsartikel (refereegranskat)abstract
- We propose the Positive Resampler to solve the problem associated with event samples from state-of-the-art predictions for scattering processes at hadron colliders typically involving a sizeable number of events contributing with negative weight. The proposed method guarantees positive weights for all physical distributions, and a correct description of all observables. A desirable side product of the method is the possibility to reduce the size of event samples produced by General Purpose Event Generators, thus lowering the resource demands for subsequent computing-intensive event processing steps. We demonstrate the viability and efficiency of our approach by considering its application to a next-to-leading order + parton shower merged prediction for the production of a W boson in association with multiple jets.
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| 8. |
- Andersen, K. H., et al.
(författare)
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The instrument suite of the European Spallation Source
- 2020
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 957
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Tidskriftsartikel (refereegranskat)abstract
- An overview is provided of the 15 neutron beam instruments making up the initial instrument suite of the European Spallation Source (ESS), and being made available to the neutron user community. The ESS neutron source consists of a high-power accelerator and target station, providing a unique long-pulse time structure of slow neutrons. The design considerations behind the time structure, moderator geometry and instrument layout are presented. The 15-instrument suite consists of two small-angle instruments, two reflectometers, an imaging beamline, two single-crystal diffractometers; one for macromolecular crystallography and one for magnetism, two powder diffractometers, and an engineering diffractometer, as well as an array of five inelastic instruments comprising two chopper spectrometers, an inverse-geometry single-crystal excitations spectrometer, an instrument for vibrational spectroscopy and a high-resolution backscattering spectrometer. The conceptual design, performance and scientific drivers of each of these instruments are described. All of the instruments are designed to provide breakthrough new scientific capability, not currently available at existing facilities, building on the inherent strengths of the ESS long-pulse neutron source of high flux, flexible resolution and large bandwidth. Each of them is predicted to provide world-leading performance at an accelerator power of 2 MW. This technical capability translates into a very broad range of scientific capabilities. The composition of the instrument suite has been chosen to maximise the breadth and depth of the scientific impact of the early years of the ESS, and provide a solid base for completion and further expansion of the facility.
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| 9. |
- Andersen, Peter M., 1962-, et al.
(författare)
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Caregivers’ divergent perspectives on patients’ well-being and attitudes towards hastened death in Germany, Poland and Sweden
- 2022
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 23:3-4, s. 252-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient’s well-being and preferences is a prerequisite for patient-centered surrogate decision making.Methods: In Germany (N = 84), Poland (N = 77) and Sweden (N = 73) patient-caregiver dyads were interviewed. Standardized questionnaires on well-being (ADI-12 for depressiveness; ACSA for global quality of life) and wish for hastened death (SAHD) were used in ALS patients. Additionally, caregivers were asked to fill out the same questionnaires by anticipating patients’ perspective (surrogate perspective).Results: Caregivers significantly underestimated patients’ well-being in Germany and Poland. For Swedish caregivers, there were just as many who underestimated and overestimated well-being. The same was true for wish for hastened death in all three countries. For Swedish and Polish patients, caregivers’ estimation of well-being was not even associated with patients’ responses and the same was true for estimation of wish for hastened death in all three countries. Older caregivers and those with the most frequent encounter with the patient were the closest in their rating of well-being and wish for hastened death to the patients’ actual state, while caregivers with chronic disease him/herself were more likely to underestimate patient’s well-being.Discussion: Despite distinct cultural differences, there was a clear discrepancy between patients’ and caregivers’ perspective on patients’ well-being and preferences towards life in all three countries. This possible bias in caregivers’ judgment needs to be taken into account in surrogate decision making.
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| 10. |
- Balmonte, John Paul, et al.
(författare)
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Sharp contrasts between freshwater and marine microbial enzymatic capabilities, community composition, and DOM pools in a NE Greenland fjord
- 2020
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Ingår i: Limnology and Oceanography. - : WILEY. - 0024-3590 .- 1939-5590. ; 65:1, s. 77-95
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Tidskriftsartikel (refereegranskat)abstract
- Increasing glacial discharge can lower salinity and alter organic matter (OM) supply in fjords, but assessing the biogeochemical effects of enhanced freshwater fluxes requires understanding of microbial interactions with OM across salinity gradients. Here, we examined microbial enzymatic capabilities-in bulk waters (nonsize-fractionated) and on particles (>= 1.6 mu m)-to hydrolyze common OM constituents (peptides, glucose, polysaccharides) along a freshwater-marine continuum within Tyrolerfjord-Young Sound. Bulk peptidase activities were up to 15-fold higher in the fjord than in glacial rivers, whereas bulk glucosidase activities in rivers were twofold greater, despite fourfold lower cell counts. Particle-associated glucosidase activities showed similar trends by salinity, but particle-associated peptidase activities were up to fivefold higher-or, for several peptidases, only detectable-in the fjord. Bulk polysaccharide hydrolase activities also exhibited freshwater-marine contrasts: xylan hydrolysis rates were fivefold higher in rivers, while chondroitin hydrolysis rates were 30-fold greater in the fjord. Contrasting enzymatic patterns paralleled variations in bacterial community structure, with most robust compositional shifts in river-to-fjord transitions, signifying a taxonomic and genetic basis for functional differences in freshwater and marine waters. However, distinct dissolved organic matter (DOM) pools across the salinity gradient, as well as a positive relationship between several enzymatic activities and DOM compounds, indicate that DOM supply exerts a more proximate control on microbial activities. Thus, differing microbial enzymatic capabilities, community structure, and DOM composition-interwoven with salinity and water mass origins-suggest that increased meltwater may alter OM retention and processing in fjords, changing the pool of OM supplied to coastal Arctic microbial communities.
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