| 1. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 2. |
- Eriksson, Lorraine, 1990-
(författare)
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Exploring genomic and phenotypic differences in Neisseria meningitidis : understanding carriage and invasive disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neisseria meningitidis can colonise the nasopharynx in humans and is also the cause of invasive meningococcal disease (IMD), which often presents as septicaemia and meningitis with high mortality rates. Invasive disease is often associated with specific capsular serogroups and clonal complexes (CC). In Sweden, serogroups Y and W have had a high incidence in recent years, but were previously considered rare causes of IMD, suggesting a change in the virulence potential of these serogroups. Currently, no specific genes exist that can reliably predict whether an N. meningitidis isolate will result in invasive disease or remain in the carriage state. Genetically similar isolates can be found during carriage and IMD, and it is more common for the carriage isolates to lack a capsule. The aim of this thesis was to investigate how genetic and phenotypic differences in N. meningitidis, can affect the virulence and the transition from a carriage state to invasive disease.The results indicate that the increase of serogroup W in Sweden is due to a specific lineage of CC11. This CC is rarely found among carriers and is considered highly virulent. Infections in transgenic mice with serogroup W CC11 isolates showed a greater virulence compared to serogroup Y isolates from other CCs. Although both serogroups are common causes of IMD in Sweden, they differ in virulence in transgenic mice. A genome-wide association study comparing carriage and invasive isolates, revealed that there were genetic variants in genes associated with virulence between these isolates. Among these variants were pilE/pilS, which are involved in the type IV pili. Comparison of pilE gene expression between carriage and invasive isolates showed no significant difference between these isolates. However, a difference in the class of the PilE protein was found between invasive and carriage isolates. Further research is needed to understand the impact of these genetic variations on the transition from carriage to invasive disease, also considering how factors in the human host and the environment that may contribute to the development of invasive disease.
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| 3. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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