| 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. |
- Lehtipalo, Katrianne, et al.
(författare)
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Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:12
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Tidskriftsartikel (refereegranskat)abstract
- A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NOx) and sulfur oxides (SOx) from fossil fuel combustion, as well as ammonia (NH3) from livestock and fertilizers. Here, we show how NOx suppresses particle formation, while HOMs, sulfuric acid, and NH3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
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| 3. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 4. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 5. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 6. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 7. |
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| 8. |
- Donini, Lorenzo M., et al.
(författare)
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Critical appraisal of definitions and diagnostic criteria for sarcopenic obesity based on a systematic review
- 2020
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 39:8, s. 2368-2388
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Forskningsöversikt (refereegranskat)abstract
- Background: Sarcopenic obesity is a clinical and functional condition characterized by the coexistence of excess fat mass and sarcopenia. Currently, different definitions of sarcopenic obesity exist and its diagnostic criteria and cut-offs are not universally established. Therefore, the prevalence and sensitivity of this condition for any disease risk prediction is affected significantly. Aim: This work was conducted under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). An international expert panel performed a systematic review as an initial step to analyze and summarize the available scientific literature on the definitions and the diagnostic criteria for sarcopenic obesity proposed and/or applied in human studies to date.Methods: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in April 2018 in three databases (PubMed, Scopus, Web of Science). Human studies conducted in both sexes, irrespective of ethnicity, and published from 2007 to 2018 were included; cohorts of individuals with obesity and acute or chronic conditions and treatments reported to negatively influence skeletal muscle mass and function independently of obesity were excluded from final analyses. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) adapted for cross sectional studies.Results: The electronic search retrieved 2335 papers of which 75 met the eligibility criteria. A marked heterogeneity in definitions and approaches to diagnose sarcopenic obesity was observed. This was mainly due to differences in the definitions of obesity and sarcopenia, in the methodologies used to assess body composition and physical function, and in the reference values for the variables that have been used (different cut-offs, interquartile analysis, diverse statistical stratification methods). This variability may be attributable, at least in part, to the availability of the methodologies in the different settings, to the variability in specialties and backgrounds of the researcher, and to the different settings (general population, clinical settings, etc.) where studies were performed.Conclusion: The results of the current work support the need for consensus proposals on: 1) definition of sarcopenic obesity; 2) diagnostic criteria both at the level of potential gold-standards and acceptable surrogates with wide clinical applicability, and with related cut-off values; 3) methodologies to be used in actions 1 and 2. First steps should be aimed at reaching consensus on plausible proposals that would need subsequent validation based on homogeneous studies and databases, possibly based on analyses of existing cohorts, to help define the prevalence of the condition, its clinical and functional relevance as well as most effective prevention and treatment strategies.
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| 9. |
- Donini, Lorenzo M., et al.
(författare)
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Definition and diagnostic criteria for sarcopenic obesity : ESPEN and EASO consensus statement
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:4, s. 990-1000
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases), and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of an universally established SO Definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes.Aims and methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a Definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into Stage I in the absence of clinical complications, or Stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction.Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO Definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition. (c) 2022 The Author(s). Published by Elsevier Ltd. on behalf of European Society for Clinical Nutrition and Metabolism and Obesity Facts published by S. Karger AG. This article is published under the Creative Commons CC-BY license. All rights reserved.
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| 10. |
- Farnocchia, Davide, et al.
(författare)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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