| 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. |
- Frantz, Laurent A. F., et al.
(författare)
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Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:35, s. 17231-17238
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological evidence indicates that pig domestication had begun by similar to 10,500 y before the present ( BP) in the Near East, and mitochondrial DNA ( mtDNA) suggests that pigs arrived in Europe alongside farmers similar to 8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
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| 5. |
- Lendaro, Eva, 1989, et al.
(författare)
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Phantom motor execution as a treatment for phantom limb pain: Protocol of an international, double-blind, randomised controlled clinical trial
- 2018
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Phantom limb pain (PLP) is a chronic condition that can greatly diminish quality of life. Control over the phantom limb and exercise of such control have been hypothesised to reverse maladaptive brain changes correlated to PLP. Preliminary investigations have shown that decoding motor volition using myoelectric pattern recognition, while providing real-time feedback via virtual and augmented reality (VR-AR), facilitates phantom motor execution (PME) and reduces PLP. Here we present the study protocol for an international (seven countries), multicentre (nine clinics), double-blind, randomised controlled clinical trial to assess the effectiveness of PME in alleviating PLP. Methods and analysis Sixty-seven subjects suffering from PLP in upper or lower limbs are randomly assigned to PME or phantom motor imagery (PMI) interventions. Subjects allocated to either treatment receive 15 interventions and are exposed to the same VR-AR environments using the same device. The only difference between interventions is whether phantom movements are actually performed (PME) or just imagined (PMI). Complete evaluations are conducted at baseline and at intervention completion, as well as 1, 3 and 6 months later using an intention-to-treat (ITT) approach. Changes in PLP measured using the Pain Rating Index between the first and last session are the primary measure of efficacy. Secondary outcomes include: Frequency, duration, quality of pain, intrusion of pain in activities of daily living and sleep, disability associated to pain, pain self-efficacy, frequency of depressed mood, presence of catastrophising thinking, health-related quality of life and clinically significant change as patient's own impression. Follow-up interviews are conducted up to 6 months after the treatment. Ethics and dissemination The study is performed in agreement with the Declaration of Helsinki and under approval by the governing ethical committees of each participating clinic. The results will be published according to the Consolidated Standards of Reporting Trials guidelines in a peer-reviewed journal.
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| 6. |
- Ortiz Catalan, Max Jair, 1982, et al.
(författare)
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Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: a single group, clinical trial in patients with chronic intractable phantom limb pain
- 2016
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Ingår i: The Lancet. - : Elsevier BV. - 1474-547X .- 0140-6736. ; 388:10062, s. 2885-2894
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Tidskriftsartikel (refereegranskat)abstract
- Background Phantom limb pain is a debilitating condition for which no eff ective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation. Methods Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specifi c frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials. gov, number NCT02281539. Findings Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically signifi cant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1 . 0 [0 . 8]; p= 0 . 001) for weighted pain distribution, 32% (38; absolute mean change 1 . 6 [1 . 8]; p= 0 . 007) for the numeric rating scale, and 51% (33; absolute mean change 9 . 6 [8 . 1]; p= 0 . 0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2 . 4 [2 . 3]; p= 0 . 004) and 61% (39; absolute mean change 2 . 3 [1 . 8]; p= 0 . 001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment. Interpretation Our fi ndings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identified side-effects at present.
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| 7. |
- Ortiz-Catalan, Max, et al.
(författare)
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Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain : a single group, clinical trial in patients with chronic intractable phantom limb pain
- 2016
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 388:10062, s. 2885-2894
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phantom limb pain is a debilitating condition for which no eff ective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation.Methods: Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specifi c frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials. gov, number NCT02281539.Findings: Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically signifi cant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1 . 0 [0 . 8]; p= 0 . 001) for weighted pain distribution, 32% (38; absolute mean change 1 . 6 [1 . 8]; p= 0 . 007) for the numeric rating scale, and 51% (33; absolute mean change 9 . 6 [8 . 1]; p= 0 . 0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2 . 4 [2 . 3]; p= 0 . 004) and 61% (39; absolute mean change 2 . 3 [1 . 8]; p= 0 . 001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment.Interpretation: Our fi ndings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identifi ed side-eff ects at present.
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| 8. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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