| 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. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 3. |
- Wright, Gillian, et al.
(författare)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Tidskriftsartikel (refereegranskat)abstract
- The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
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| 4. |
- Scott, James S., et al.
(författare)
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Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
- 2014
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998
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Tidskriftsartikel (refereegranskat)abstract
- Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
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| 5. |
- Titov, Nickolai, et al.
(författare)
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User characteristics and outcomes from a national digital mental health service : an observational study of registrants of the Australian MindSpot Clinic.
- 2020
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Ingår i: The Lancet Digital Health. - London, United Kingdom : The Lancet Publishing Group. - 2589-7500. ; 2:11, s. e582-e593
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation.Methods: We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment.Outcomes: A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role.Interpretation: Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems.Funding: None.
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| 6. |
- Andersson, Erik, et al.
(författare)
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Innovations in digital interventions for psychological trauma : harnessing advances in cognitive science.
- 2018
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Ingår i: mHealth. - : AME Publishing Company. - 2306-9740. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- A range of digital psychological interventions have demonstrated a positive impact on trauma-related problems in controlled trials, but there is room for further improvements in their form, reach and impact. Most to date have been adaptions of established face-to-face treatments. In this paper, we highlight a complementary emerging route to their development, which draws on advances in cognitive science theory and research and applies them to clinical contexts. Three examples are given regarding laboratory research with potential applications to digital interventions for trauma-related mental health problems: a digital game to reduce intrusive memories of trauma, novel cognitive techniques for worry, and digitally supported mental imagery to enhance motivation for functional behavior change. Much of this research is still at an early stage, meriting a balance of optimism and caution. However, even if only a few digital applications of cognitive science constitute substantial improvements to complement current treatments, their potential for large-scale use at low unit cost may provide significant benefits across populations.
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| 7. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 8. |
- Blom, Anna M, et al.
(författare)
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A Novel Non-Synonymous Polymorphism (p.Arg240His) in C4b-Binding Protein Is Associated with Atypical Hemolytic Uremic Syndrome and Leads to Impaired Alternative Pathway Cofactor Activity.
- 2008
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Ingår i: Journal of Immunology. - 1550-6606. ; 180:9, s. 6385-6391
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Tidskriftsartikel (refereegranskat)abstract
- Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (chi2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.
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| 9. |
- Cereda, Maurizio, et al.
(författare)
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Imaging the Injured Lung : Mechanisms of Action and Clinical Use
- 2019
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Ingår i: Anesthesiology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-3022 .- 1528-1175. ; 131:3, s. 716-749
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Forskningsöversikt (refereegranskat)abstract
- Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung. This review also describes newer imaging methodologies that are likely to inform future clinical decision-making and potentially improve outcome. For each imaging modality, this review systematically describes the underlying principles, technology involved, measurements obtained, insights gained by the technique, emerging approaches, limitations, and future developments. Finally, integrated approaches are considered whereby multimodal imaging may impact management of ARDS.
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| 10. |
- Di Simplicio, Martina, et al.
(författare)
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Imaginator : A Proof-of-Concept Feasibility Trial of a Brief Imagery-Based Psychological Intervention for Young People Who Self-Harm
- 2020
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Ingår i: Journal of Suicide and Life-threatening Behaviour. - : Wiley. - 0363-0234 .- 1943-278X. ; 50:3, s. 724-740
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Imaginator study tested the feasibility of a short mental imagery‐based psychological intervention for young people who self‐harm and used a stepped‐wedge design to investigate effects on self‐harm frequency reduction at 3 and 6 months.Method: A total of 38 participants aged 16–25 were recruited via community self‐referral and mental health services. Participants were randomized to immediate delivery of Functional Imagery Training (FIT) or usual care followed by delayed delivery after 3 months. FIT comprised two face‐to‐face sessions, five phone sessions, and use of a smartphone app. Outcomes’ assessment was blind to allocation.Results: Three quarters of those who began treatment completed face‐to‐face sessions, and 57% completed five or more sessions in total. Self‐harm frequency data were obtained on 76% of the sample at 3 months (primary outcome) and 63% at 6 months. FIT produced moderate reductions in self‐harm frequency at 3 months after immediate (d = 0.65) and delayed delivery (d = 0.75). The Immediate FIT group maintained improvements from 3 to 6 months (d = 0.05). Participants receiving usual care also reduced self‐harm (d = 0.47).Conclusions: A brief mental imagery‐based psychological intervention targeting self‐harm in young people is feasible and may comprise a novel transdiagnostic treatment for self‐harm.
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