An official website of the United States government
Background:Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects. Methods:We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results:We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions:These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding:This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016–0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 – 2056) (FXV). Clinical trial number:NCT03842800
more »
« less
This content will become publicly available on November 18, 2025
Testing for reviewer anchoring in peer review: A randomized controlled trial
ObjectivePeer review frequently follows a process where reviewers first provide initial reviews, authors respond to these reviews, then reviewers update their reviews based on the authors’ response. There is mixed evidence regarding whether this process is useful, including frequent anecdotal complaints that reviewers insufficiently update their scores. In this study, we aim to investigate whether reviewersanchorto their original scores when updating their reviews, which serves as a potential explanation for the lack of updates in reviewer scores. DesignWe design a novel randomized controlled trial to test if reviewers exhibit anchoring. In the experimental condition, participants initially see a flawed version of a paper that is corrected after they submit their initial review, while in the control condition, participants only see the correct version. We take various measures to ensure that in the absence of anchoring, reviewers in the experimental group should revise their scores to be identically distributed to the scores from the control group. Furthermore, we construct the reviewed paper to maximize the difference between the flawed and corrected versions, and employ deception to hide the true experiment purpose. ResultsOur randomized controlled trial consists of 108 researchers as participants. First, we find that our intervention was successful at creating a difference in perceived paper quality between the flawed and corrected versions: Using a permutation test with the Mann-WhitneyUstatistic, we find that the experimental group’s initial scores are lower than the control group’s scores in both the Evaluation category (Vargha-DelaneyA= 0.64,p= 0.0096) and Overall score (A= 0.59,p= 0.058). Next, we test for anchoring by comparing the experimental group’s revised scores with the control group’s scores. We find no significant evidence of anchoring in either the Overall (A= 0.50,p= 0.61) or Evaluation category (A= 0.49,p= 0.61). The Mann-WhitneyUrepresents the number of individual pairwise comparisons across groups in which the value from the specified group is stochastically greater, while the Vargha-DelaneyAis the normalized version in [0, 1].
more »
« less
- PAR ID:
- 10570455
- Editor(s):
- Leitner, Stephan
- Publisher / Repository:
- PLOS ONE
- Date Published:
- Journal Name:
- PLOS ONE
- Volume:
- 19
- Issue:
- 11
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0301111
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract ObjectivesMagnitudes of morphological integration may constrain or facilitate craniofacial shape variation. The aim of this study was to analyze how the magnitude of integration in the skull ofMacaca fascicularischanges throughout ontogeny in relation to developmental and/or functional modules. Materials and methodsGeometric morphometric methods were used to analyze the magnitude of integration in the macaque cranium and mandible in 80 juvenile and 40 adultM. fascicularisspecimens. Integration scores in skull modules were calculated using integration coefficient of variation (ICV) of eigenvalues based on a resampling procedure. Resultant ICV scores between the skull as a whole, and developmental and/or functional modules were compared using Mann–WhitneyUtests. ResultsResults showed that most skull modules were more tightly integrated than the skull as a whole, with the exception of the chondrocranium in juveniles without canines, the chondrocranium/face complex and the mandibular corpus in adults, and the mandibular ramus in all juveniles. The chondrocranium/face and face/mandibular corpus complexes were more tightly integrated in juveniles than adults, possibly reflecting the influences of early brain growth/development, and the changing functional demands of infant suckling and later masticatory loading. This is also supported by the much higher integration of the mandibular ramus in adults compared with juveniles. DiscussionMagnitudes of integration in skull modules reflect developmental/functional mechanisms inM. fascicularis. However, the relationship between “evolutionary flexibility” and developmental/functional mechanisms was not direct or simple, likely because of the complex morphology, multifunctionality, and various ossification origins of the skull.more » « less
-
ImportanceAssessing nontechnical skills in operating rooms (ORs) is crucial for enhancing surgical performance and patient safety. However, automated and real-time evaluation of these skills remains challenging. ObjectiveTo explore the feasibility of using motion features extracted from surgical video recordings to automatically assess nontechnical skills during cardiac surgical procedures. Design, Setting, and ParticipantsThis cross-sectional study used video recordings of cardiac surgical procedures at a tertiary academic US hospital collected from January 2021 through May 2022. The OpenPose library was used to analyze videos to extract body pose estimations of team members and compute various team motion features. The Non-Technical Skills for Surgeons (NOTSS) assessment tool was employed for rating the OR team’s nontechnical skills by 3 expert raters. Main Outcomes and MeasuresNOTSS overall score, with motion features extracted from surgical videos as measures. ResultsA total of 30 complete cardiac surgery procedures were included: 26 (86.6%) were on-pump coronary artery bypass graft procedures and 4 (13.4%) were aortic valve replacement or repair procedures. All patients were male, and the mean (SD) age was 72 (6.3) years. All surgical teams were composed of 4 key roles (attending surgeon, attending anesthesiologist, primary perfusionist, and scrub nurse) with additional supporting roles. NOTSS scores correlated significantly with trajectory (r = 0.51,P = .005), acceleration (r = 0.48,P = .008), and entropy (r = −0.52,P = .004) of team displacement. Multiple linear regression, adjusted for patient factors, showed average team trajectory (adjustedR2 = 0.335; coefficient, 10.51 [95% CI, 8.81-12.21];P = .004) and team displacement entropy (adjustedR2 = 0.304; coefficient, −12.64 [95% CI, −20.54 to −4.74];P = .003) were associated with NOTSS scores. Conclusions and RelevanceThis study suggests a significant link between OR team movements and nontechnical skills ratings by NOTSS during cardiac surgical procedures, suggesting automated surgical video analysis could enhance nontechnical skills assessment. Further investigation across different hospitals and specialties is necessary to validate these findings.more » « less
-
BackgroundRisk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening. Methods and findingsFor model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis.Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables—age, smoking duration, and pack-years—achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts. ConclusionsWe present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings.more » « less
-
Modern machine learning and computer science conferences are experiencing a surge in the number of submissions that challenges the quality of peer review as the number of competent reviewers is growing at a much slower rate. To curb this trend and reduce the burden on reviewers, several conferences have started encouraging or even requiring authors to declare the previous submission history of their papers. Such initiatives have been met with skepticism among authors, who raise the concern about a potential bias in reviewers' recommendations induced by this information. In this work, we investigate whether reviewers exhibit a bias caused by the knowledge that the submission under review was previously rejected at a similar venue, focusing on a population of novice reviewers who constitute a large fraction of the reviewer pool in leading machine learning and computer science conferences. We design and conduct a randomized controlled trial closely replicating the relevant components of the peer-review pipeline with $133$ reviewers (master's, junior PhD students, and recent graduates of top US universities) writing reviews for $19$ papers. The analysis reveals that reviewers indeed become negatively biased when they receive a signal about paper being a resubmission, giving almost 1 point lower overall score on a 10-point Likert item (Δ = -0.78, 95% CI = [-1.30, -0.24]) than reviewers who do not receive such a signal. Looking at specific criteria scores (originality, quality, clarity and significance), we observe that novice reviewers tend to underrate quality the most.more » « less
