Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.

Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8+ T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Protective CD8+ T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness.

Variability across subjects in free recall versus cued recall.

Memory scientists usually compare mean performance on some measure(s) (accuracy, confidence, latency) as a function of experimental condition. Some researchers have made within-subject variability in task performance a focal outcome measure (e.g., Yao et al., Journal of Clinical and Experimental Neuropsychology, 38, 227-237, 2016). Here, we explored between-subject variability in accuracy as a function of experimental conditions. This work was inspired by an incidental finding in a previous study, in which we observed greater variability in accuracy of memory performance on cued recall (CR) versus free recall (FR) of English animal/object nouns (Mah et al., Frontiers in Psychology, 14, 1146200, 2023). Here we report experiments designed to assess the reliability of that pattern and to explore its causes (e.g., differential interpretation of instructions, [un]relatedness of CR word pairs, encoding time). In Experiment 1 (N = 120 undergraduates), we replicated the CR:FR variability difference with a more representative set of English nouns. In Experiments 2A (N = 117 Prolific participants) and 2B (N = 127 undergraduates), we found that the CR:FR variability difference persisted in a forced-recall procedure. In Experiment 3 (N = 260 Prolific participants), we used meaningfully related word pairs and still found greater variability in CR than in FR performance. In Experiment 4 (N = 360 Prolific participants), we equated CR and FR study phases by having all participants study pairs and, again, observed greater variability in CR than FR. The same was true in Experiment 5 (N = 120 undergraduates), in which study time was self-paced. Comparisons of variability across subjects can yield insights into the mechanisms underlying task performance.

Stakeholder Reflections on Implementing the National Institutes of Health's Policy on Single Institutional Review Boards.

The National Institutes of Health (NIH) requires use of a single institutional review board (sIRB) for multisite, nonexempt, NIH-funded research with human participants. The Clinical Trials Transformation Initiative (CTTI) conducted in-depth interviews with 34 stakeholders at two universities and in research administration leadership positions at multiple institutions about their experiences implementing the sIRB model, focusing on the NIH policy's goals soon after the policy was enacted. While some stakeholders suggested that using an sIRB has streamlined and reduced inefficiencies associated with the local IRB model, more stakeholders indicated that the sIRB model has not simplified the ethics review process and instead created new inefficiencies due to unclear roles and responsibilities for staff and institutions; a lack of systems and processes for implementing the sIRB model, including communication systems; and increased workloads. CTTI used these findings to propose a new framework for evaluating the NIH sIRB policy.

A direct replication and extension of Popp and Serra (2016, experiment 1): better free recall and worse cued recall of animal names than object names, accounting for semantic similarity.

Introduction: Free recall tends to be better for names of animate concepts such as animals than for names of inanimate objects. In Popp and Serra's 2016 article, the authors replicated this "animacy effect" in free recall but when participants studied words in pairs (animate-animate pairs intermixed with inanimate-inanimate pairs) and were tested with cued recall, performance was better for inanimate-inanimate pairs than for animate-animate pairs ("reverse animacy"). We tested the replicability of this surprising effect and one possible explanation for the effect (semantic similarity). Methods: Our Experiment 1 was a preregistered direct replication (N = 101) of Popp and Serra's Experiment 1 (mixed-lists condition). In a second preregistered experiment conducted in four different samples (undergraduate N = 153, undergraduate N = 143, online Prolific N = 101, online Prolific/English-as-a-first-language N = 150), we manipulated the within-category semantic similarity of animal and object wordlists. Results: AIn Experiment 1, just as in Popp and Serra, we observed an animacy effect for free recall and a reverse animacy effect for cued recall. Unlike Popp and Serra, we found that controlling for interference effects rendered the reverse animacy effect non-significant. We took this as evidence that characteristics of the stimulus sets (e.g., category structure, within-category similarity) may play a role in animacy and reverse animacy effects. In Experiment 2, in three out of our four samples, we observed reverse animacy effects when within-category similarity was higher for animals and when within-category similarity was equated for animals and objects. Discussion: Our results suggest that the reverse animacy effect observed in Popp and Serra's 2016 article is a robust and replicable effect, but that semantic similarity alone cannot explain the effect.

Mixed News about the Bad News Game.

Basol et al. (2020) tested the "the Bad News Game" (BNG), an app designed to improve ability to spot false claims on social media. Participants rated simulated Tweets, then played either the BNG or an unrelated game, then re-rated the Tweets. Playing the BNG lowered rated belief in false Tweets. Here, four teams of undergraduate psychology students each attempted an extended replication of Basol et al., using updated versions of the original Bad News game. The most important extension was that the replications included a larger number of true Tweets than the original study and planned analyses of responses to true Tweets. The four replications were loosely coordinated, with each team independently working out how to implement the agreed plan. Despite many departures from the Basol et al. method, all four teams replicated their key finding: Playing the BNG reduced belief in false Tweets. But playing the BNG also reduced belief in true Tweets to the same or almost the same extent. Exploratory signal detection theory analyses indicated that the BNG increased response bias but did not improve discrimination. This converges with findings reported by Modirrousta-Galian and Higham (2023).

The effect of pre-event instructions on eyewitness identification.

Research on eyewitness identification often involves exposing participants to a simulated crime and later testing memory using a lineup. We conducted a systematic review showing that pre-event instructions, instructions given before event exposure, are rarely reported and those that are reported vary in the extent to which they warn participants about the nature of the event or tasks. At odds with the experience of actual witnesses, some studies use pre-event instructions explicitly warning participants of the upcoming crime and lineup task. Both the basic and applied literature provide reason to believe that pre-event instructions may affect eyewitness identification performance. In the current experiment, we tested the impact of pre-event instructions on lineup identification decisions and confidence. Participants received non-specific pre-event instructions (i.e., "watch this video") or eyewitness pre-event instructions (i.e., "watch this crime video, you'll complete a lineup later") and completed a culprit-absent or -present lineup. We found no support for the hypothesis that participants who receive eyewitness pre-event instructions have higher discriminability than participants who receive non-specific pre-event instructions. Additionally, confidence-accuracy calibration was not significantly different between conditions. However, participants in the eyewitness condition were more likely to see the event as a crime and to make an identification than participants in the non-specific condition. Implications for conducting and interpreting eyewitness identification research and the basic research on instructions and attention are discussed.

A framework and road map for rapid start-up and completion of a COVID-19 vaccine trial: A single clinical trial site experience.

The COVID-19 global pandemic required the rapid development of vaccines with a quick start up of phase 1-3 studies with large enrollment targets. The University of California San Diego was identified as a site for the phase 3 trial of the mRNA-1273-SARS-CoV-2 vaccine. There were many challenges with scaling up a large-scale clinical trial in such a short time. This report describes the processes and procedures that were implemented to successfully complete the enrollment target in under 10 weeks. This required the team to identify existing tools that could rapidly be accessed to develop a database, scheduling system, effective communication, document management, staff time tracking/efficiency, subject scheduling/tracking, project management, and accrual/study performance. The outcome of these efforts resulted in rapid enrollment and study completion in a short time. The lessons learned from this experience can be used by other clinical trial sites faced with similar challenges.

First meeting in Asia of the Asia Pacific Research Integrity network.

In 2017, the University of Hong Kong and the University of California San Diego co-hosted the first Asian meeting of the recently formed Asia Pacific Research Integrity (APRI) network in Hong Kong. Aligned with planning meetings in 2015 and 2016 funded in part by the US Office of Research Integrity (ORI), the Hong Kong meeting was designed by a multi-national planning committee to address pressing challenges in research integrity: improving multi-national communication; exchanging information on managing misconduct investigations; and sharing best practices to promote research integrity. To create a sustainable, robust international partnership to promote research integrity in the region, the purpose of this 2017 meeting was to foster multi-national awareness, understanding, and opportunities for collaboration. The meeting was defined by four objectives that emerged from the previous meetings: (1) Articulate differences as well as areas of common ground; (2) Identify best or recommended practices; (3) Identify opportunities for research or collaboration; and (4) Set an APRI network agenda for coming years. The key anticipated outcome was to advance the conversation surrounding research integrity among academic institutions and regulators in Asian and Pacific Rim nations. This outcome was evidenced by meeting participation, participant satisfaction, and articulation of next steps for the APRI network.