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In the last 50 years, the field of paleobiology has undergone a computational revolution that opened multiple new avenues for recording, storing, and analyzing vital data on the history of life on Earth. With these advances, the amount of data available for research has grown, but so too has our responsibility to ensure that our data tools and infrastructures continue to innovate in order to best serve our diverse community. This review focuses on data equity in paleobiology, an aspirational goal, wherein data in all forms are collected, stored, shared and analyzed in a responsible, equitable, and sustainable manner. While there have been many advancements across the last five decades, inequities persist. Our most significant challenges relate to several interconnected factors, including ethical data collection, sustainable infrastructure, socioeconomic biases, and global inequalities. We highlight the ways in which data equity is critical for paleobiology and stress the need for collaborative efforts across the paleobiological community to urgently address these data equity challenges. We also provide recommendations for actions from individuals, teams, academic publishers, and academic societies in order to continue enhancing data equity and ensuring an equitable and sustainable future for our field.
Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.
Objectives/Goals: Our research goal is to translate medical guidelines for adolescent-centered contraceptive counseling into improved clinical practice. Here, we describe the process of co-designing a training program for adolescent-serving primary care clinicians with teen, caregiver, and clinician advisory boards. Methods/Study Population: We recruited teens, caregivers, and clinicians residing in North Carolina to participate in three virtual advisory boards separated by role. Eligible teen advisors were assigned female at birth and 15–19 years old; eligible clinicians provided care for teen patients; and all groups were purposively sampled to reflect diverse identities and experiences. At each advisor meeting, we used human-centered design techniques to elicit participant priorities, generate training content and engagement strategies, and obtain feedback on the final training program. We conducted a focus group at our final meetings and used rapid qualitative analysis to understand our advisors’ experiences participating in program co-development. Results/Anticipated Results: We partnered with 20 advisors with diverse identities across geographic location, race and ethnicity, sexuality, and experiences with disability. During 15 meetings from January to May 2024 (five with each advisor group), we developed a 3-hour virtual, synchronous training for adolescent-serving primary care providers to improve their contraceptive counseling skills. The curriculum includes five interactive modules and a resource toolkit. Advisors described motivations to participate (e.g., chance to share their perspective, desire to make change), positive experiences with the advisory boards (e.g., opportunities to learn, to connect with others), and opportunities for improvement (e.g., better technology orientation). Discussion/Significance of Impact: We describe developing a successful longitudinal partnership with three community advisory boards and co-creating a training program that incorporates community-led priorities and perspectives, including youth. This approach can be adapted for other clinician training programs seeking to center community voices.
Objectives/Goals: To evaluate equity in utilization of free initial health evaluation (IHE) services among members of a limited health care program, the World Trade Center (WTC) Health Program (Program), to inform intervention development and provide insights for similar healthcare programs. Methods/Study Population: We included Program members who newly enrolled during 2012–2022, and who had an IHE or were alive for ≥ 1 year after enrollment. Program administrative and surveillance data collected from January 2012 to February 2024 were used. We evaluated two outcomes: timely IHE utilization (proportion of members completing an IHE within 6 months of enrollment) and any IHE utilization (proportion completing an IHE by February 2024). We described IHE utilization by enrollment year and various members’ characteristics and conducted multivariable logistic regression models to estimate adjusted odds ratios for IHE utilizations to identify factors related to potential inequities for the two member types: Responders, who performed support services, vs. Survivors, who did not respond but were present in the New York disaster area. Results/Anticipated Results: A total of 27,379 Responders and 30,679 Survivors were included. Responders were 89% male, 70% 45–64 years old at enrollment and 76% White. Survivors were 46% female, 54% 45–64 years old at enrollment, and 57% White. Timely IHE utilizations remained relatively stable (~65%) among Responders across time and increased from 16% among Survivors who enrolled in 2017 to 68% among Survivors who enrolled in 2021. Timely IHE utilization was lower for younger members (enrolled Discussion/Significance of Impact: This study highlights Program achievements and gaps in providing equitable IHE services. Strategies to improve members’ equitable IHE utilization can include: adopt/expand flexible scheduling; increase non-English language capacity and cultural competency; and facilitate transportation/assistance for members with accessibility barriers.
Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Shakespeare Survey is a yearbook of Shakespeare studies and production. Since 1948, Survey has published the best international scholarship in English and many of its essays have become classics of Shakespeare criticism. Each volume is devoted to a theme, or play, or group of plays; each also contains a section of reviews of that year's textual and critical studies and of the year's major British performances. The theme for Volume 77 is 'Shakespeare's Poetry'. The complete set of Survey volumes is also available online at www.cambridge.org/core/publications/collections/cambridge-shakespeare. This searchable resource enables users to browse by author, essay and volume, search by play, theme and topic, and save and bookmark their results.
Archaeological sites in Northwest Africa are rich in human fossils and artefacts providing proxies for behavioural and evolutionary studies. However, these records are difficult to underpin on a precise chronology, which can prevent robust assessments of the drivers of cultural/behavioural transitions. Past investigations have revealed that numerous volcanic ash (tephra) layers are interbedded within the Palaeolithic sequences and likely originate from large volcanic eruptions in the North Atlantic (e.g. the Azores, Canary Islands, Cape Verde). Critically, these ash layers offer a unique opportunity to provide new relative and absolute dating constraints (via tephrochronology) to synchronise key archaeological and palaeoenvironmental records in this region. Here, we provide an overview of the known eruptive histories of the potential source volcanoes capable of widespread ashfall in the region during the last ~300,000 years, and discuss the diagnostic glass compositions essential for robust tephra correlations. To investigate the eruption source parameters and weather patterns required for ash dispersal towards NW Africa, we simulate plausible ashfall distributions using the Ash3D model. This work constitutes the first step in developing a more robust tephrostratigraphic framework for distal ash layers in NW Africa and highlights how tephrochronology may be used to reliably synchronise and date key climatic and cultural transitions during the Palaeolithic.
Seismic imaging in 3-D holds great potential for improving our understanding of ice sheet structure and dynamics. Conducting 3-D imaging in remote areas is simplified by using lightweight and logistically straightforward sources. We report results from controlled seismic source tests carried out near the West Antarctic Ice Sheet Divide investigating the characteristics of two types of surface seismic sources, Poulter shots and detonating cord, for use in both 2-D and 3-D seismic surveys on glaciers. Both source types produced strong basal P-wave and S-wave reflections and multiples recorded in three components. The Poulter shots had a higher amplitude for low frequencies (<10 Hz) and comparable amplitude at high frequencies (>50 Hz) relative to the detonating cord. Amplitudes, frequencies, speed of source set-up, and cost all suggested Poulter shots to be the preferred surface source compared to detonating cord for future 2-D and 3-D seismic surveys on glaciers.
This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation.
Method
An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice.
Results
Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise.
Conclusion
Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.
OBJECTIVES/GOALS: The goal of this study is to develop a multi-centered Translational Studio model that can help in the development of quality translational studies using resources from four different institutional partners (University of Texas Medical Branch, Texas Southern University, University of Houston Clear Lake and Houston Methodist). METHODS/STUDY POPULATION: We conducted two rounds of four Futures Workshops for a total participation of 28 stakeholders from four different partners. Future Workshops were used to critique, envision, and articulate novel “futures” that can be achieved at least partly through design practices (Muller, 2002). In the first round of workshops, we asked participants about their institutions’ strengths, weaknesses, resources and investigator needs regarding the Studio. In the second round we asked about different studio models, pros and cons of each model and guiding principles for a studio. Alongside a pragmatic content analysis, multi-stage deductive and inductive qualitative analyses were used to understand people’s views on the future of a multi-institutional Clinical Trials Studio. RESULTS/ANTICIPATED RESULTS: The first-round workshops’ analysis described peoples’ goals for what the studio should be. The future desired studio was described as guide, matchmaker, initiator and advocate. The second-round workshops’ analysis discussed the pros and cons of a variety of possible models including, centralized, decentralized, and topic-specific (and allowed other suggestions) while also describing principles for the guidance of a studio. Here the analysis showed people wanted certain characteristics for the studio (i.e. effective, efficient, locally-responsive, consistent, etc.). They also prescribed four principles that a studio should be guided by: non-hierarchical partnership, user-centeredness, respect/collegiality, and sharing. DISCUSSION/SIGNIFICANCE: The future workshops were useful in developing a shared multi-institutional Clinical Trials Studio model that is planned to be deployed in 2025. Participants valued a studio that was both directly supportive to participants and played a role in creating or advocating for institutional resources and policy for research.