| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 3. |
- Hoban, Sean, et al.
(författare)
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Genetic diversity goals and targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework
- 2023
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 24:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity’s (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.
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| 4. |
- Bertola, Laura D., et al.
(författare)
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A pragmatic approach for integrating molecular tools into biodiversity conservation
- 2024
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Ingår i: Conservation science and practice. - 2578-4854. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation. Molecular tools are increasingly applied in conservation management; however, they are not equally available to all practitioners. We here provide key questions when establishing a conservation genetic study and highlight important steps which need to be addressed when these tools are globally applied.image
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| 5. |
- Currie, Thayne, et al.
(författare)
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Direct imaging and astrometric detection of a gas giant planet orbiting an accelerating star
- 2023
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 380:6641, s. 198-203
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Tidskriftsartikel (refereegranskat)abstract
- Direct imaging of gas giant exoplanets provides information on their atmospheres and the architectures of planetary systems. However, few planets have been detected in blind surveys with direct imaging. Using astrometry from the Gaia and Hipparcos spacecraft, we identified dynamical evidence for a gas giant planet around the nearby star HIP 99770. We confirmed the detection of this planet with direct imaging using the Subaru Coronagraphic Extreme Adaptive Optics instrument. The planet, HIP 99770 b, orbits 17 astronomical units from its host star, receiving an amount of light similar to that reaching Jupiter. Its dynamical mass is 13.9 to 16.1 Jupiter masses. The planet-to-star mass ratio [(7 to 8) × 10−3] is similar to that of other directly imaged planets. The planet’s atmospheric spectrum indicates an older, less cloudy analog of the previously imaged exoplanets around HR 8799.
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| 6. |
- D'Souza, Nigel, et al.
(författare)
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Definition of the Rectum An International, Expert-based Delphi Consensus
- 2019
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 270:6, s. 955-959
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Tidskriftsartikel (refereegranskat)abstract
- Background: The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment. Methods: The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018. Results: Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was "the sigmoid take-off,'' an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark. Conclusion: An international consensus definition for the rectumis the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation.
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| 7. |
- Greijdanus, Nynke G., et al.
(författare)
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Stoma-free survival after anastomotic leak following rectal cancer resection : worldwide cohort of 2470 patients
- 2023
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 110:12, s. 1863-1876
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied.METHODS: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1).RESULTS: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days).CONCLUSION: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.
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| 8. |
- Greijdanus, Nynke G., et al.
(författare)
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Stoma-free survival after rectal cancer resection with anastomotic leakage : development and validation of a prediction model in a large international cohort
- 2023
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 278:5, s. 772-780
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL).Background: AL after RC resection often results in a permanent stoma.Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated.Results: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76).Conclusions: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies.
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| 9. |
- Henderson, Neil C., et al.
(författare)
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Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:12, s. 1617-1624
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Tidskriftsartikel (refereegranskat)abstract
- Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta(3), beta(5) or beta(6) integrins or conditional loss of beta(8) integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
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| 10. |
- Lacy, Michael, et al.
(författare)
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Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.
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