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We present a dataset of 1,119 radiocarbon dates and their contexts for Oaxaca, Mexico, a best effort to include all published dates, plus hundreds of unpublished samples. We illustrate its potential and limitations with five examples: (1) dated stratigraphy in stream cutbanks show how aggradation, downcutting, and stability responded to global climate and human activities; (2) 14C samples from Late/Terminal Formative contexts allow interregional comparisons of temple and palace construction, use, and abandonment; (3) new 14C dates provide better understanding of events during the Late Classic/Epiclassic, a problematic time in the ceramic chronology; (4) individual Classic/Postclassic residential contexts had long durations—several hundred years; and (5) model constraints from other data permit refinement at times of calibration curve deviation, as during AD 1400–1600. We recommend further chronological refinement with best-practice standards, new samples, existing collections, and statistical modeling.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Tufts Clinical and Translational Science Institute (CTSI) developed an online self-paced course to address the gap identified in critical thinking skills related to peer-reviewed nutrition science publications. Initial engagement was low, prompting the launch of a quality improvement project utilizing Dissemination and Implementation (D&I) science principles to enhance participation. This report details the development and execution of the dissemination strategy, course promotion methods, and outcomes related to participant engagement and feedback.
Methods:
A dissemination plan was designed and implemented using the Value-Added Research Dissemination Framework and the Consolidated Framework for Implementation Research (CFIR). Dissemination efforts targeted registered dietitians and university nutrition program instructors, along with their students.
Results:
During the active dissemination period from January to May 2023, the cumulative numbers of learners increased from 23 to 118. Instructors from three nutrition degree programs found the course valuable, reporting that it introduced new content or reinforced existing material. Learner participation continued past the active dissemination period into 2024. Findings from the course evaluation survey provided insights to guide future course improvements.
Conclusion:
This project demonstrates the successful use of D&I frameworks to support the dissemination and implementation of educational innovations such as online learning initiatives.
The Students Participating as Ambassadors for Research in Kentucky (SPARK) program provides novel health equity research training and targeted mentorship for undergraduates, particularly those from groups underrepresented in the biomedical and behavioral research and workforce. SPARK aims to address inadequate diversity in the medical and scientific research fields by providing comprehensive research mentorship and skill-building. Unlike most existing research training programs that are brief, focus on laboratory research, or are limited to graduate students and junior faculty, SPARK delivers a 16-month intensive behavioral and population health science training, equipping students with needed tools to conceptualize, plan, execute, and analyze their own health equity research study. Trainees complete didactic coursework on health equity, study design and proposal development, data analysis, and ethics. Students receive a stipend and research expenses, and multiple mentors guide them in creating original research projects for which they serve as Principal Investigator. Students disseminate their findings annually at an academic research conference as a capstone. Evaluation data from the first three cohorts suggest SPARK has been pivotal in preparing students for graduate studies and research careers in health equity and behavioral and population health sciences, providing strong support for further investments in similar undergraduate research training models.
The maintenance of cross-cultural variation and arbitrary traditions in human populations is a key question in cultural evolution. Conformist transmission, the tendency to follow the majority, was previously considered central to this phenomenon. However, recent theory indicates that cognitive biases can greatly reduce its ability to maintain traditions. Therefore, we expanded prior models to investigate two other ways that cultural variation can be sustained: payoff-biased transmission and norm reinforcement. Our findings predict that both payoff-biased transmission and reinforcement can enhance conformist transmission's ability to maintain traditions. However, payoff-biased transmission can only sustain cultural variation if it is functionally related to environmental factors. In contrast, norm reinforcement readily generates and maintains arbitrary cultural variation. Furthermore, reinforcement results in path-dependent cultural dynamics, meaning that historical traditions influence current practices, even though group behaviours have changed. We conclude that environmental variation probably plays a role in functional cultural traditions, but arbitrary cultural variation is more plausibly due to the reinforcement of norm compliance.
SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.
A growing number of institutions that hold cultural heritage artifacts are now considering voluntary repatriations in which they choose to return an artifact despite unfilled gaps in their knowledge of its ownership history. But how are institutions to judge whether it is more probable that such gaps conceal theft and illicit export or are innocuous? Attempting to answer this question for Nepal, we examine published and archival records to trace the history of the growth in collecting of Nepali cultural heritage in the United States, with special attention to a 1964 exhibition at New York’s Asia Society Gallery, “The Art of Nepal,” and the activity of the New York dealers Nasli and Alice Heeramaneck. We conclude that the majority of Nepali heritage items in America entered after Nepal prohibited their export.
Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
The figure of Anthony Comstock may seem like an odd historical relic: a repressed, puritanical, anti-sex reformer from a bygone past. And yet, because his namesake act has been revived as a potential strategy for limiting access to reproductive healthcare, Comstock is no joke. Today, some Americans see the Comstock Act, passed by Congress in 1873, as a pathway to banning abortion and other reproductive care, effectively jettisoning any need for new Supreme Court abortion rulings or congressional legislation. As scholars of the Gilded Age and Progressive Era, we are uniquely situated to intervene in this dialogue and ensure that contemporary conversations are grounded in historical context. We present this forum not as an exhaustive account of the Comstock Act and its architect, but as aopportunity to highlight the context in which this law, which holds so much potential relevance for our present, was created, enacted, enforced, and challenged. We hope this forum will stimulate further scholarly and public conversations around the nation’s long history of regulating reproductive rights and how that history became entangled with other social anxieties.
This article presents a framework of ethical analysis for anticipatory evaluation of advanced biopreservation technologies and employs the framework illustratively in three domains. The framework features four clusters of general ethical considerations: (1) Producing Benefits, Minimizing Harms, Balancing Benefits, Risk, and Costs; (2) Justice, Fairness, Equity; (3) Respect for Autonomy; and (4) Transparency, Trustworthiness, and Public Trust.
Advanced biopreservation technologies using subzero approaches such as supercooling, partial freezing, and vitrification with reanimating techniques including nanoparticle infusion and laser rewarming are rapidly emerging as technologies with potential to radically disrupt biomedicine, research, aquaculture, and conservation. These technologies could pause biological time and facilitate large-scale banking of biomedical products including organs, tissues, and cell therapies.
Circular shell rings along the South Atlantic coast of the United States are vestiges of the earliest sedentary villages in North America, dating to 4500–3000 BP. However, little is known about when Indigenous communities began constructing these shell-ring villages. This article presents data from the Hokfv-Mocvse Shell Ring on Ossabaw Island, Georgia. Although shell rings are often associated with the earliest ceramics in North America, no ceramics were encountered in our excavations at Hokfv-Mocvse, and the only materials recovered were projectile points similar to points found over 300 km inland. Bayesian modeling of radiocarbon dates indicates that the ring was occupied between 5090 and 4735 cal BP (95% confidence), making it the earliest dated shell ring in the region. Additionally, shell geochemistry and oyster paleobiology data suggest that inhabitants were living at the ring year-round and had established institutions at that time to manage oyster fisheries sustainably. Hokfv-Mocvse therefore provides evidence for Indigenous people settling in year-round villages and adapting to coastal environments in the region centuries before the adoption of pottery. The establishment of villages marks a visible archaeological shift toward settling down and occupying island ecosystems on a more permanent basis and in larger numbers than ever before in the region.
Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia.
Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing.
The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)].
These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism.
Quantitative analysis of clay minerals by X-ray powder diffraction requires oriented clays in order to increase detection limits of the analyses. This is achieved commonly either by smear or sedimentation techniques; however, these techniques can lead to poor analytical precision when used with an internal standard because they often produce non-homogeneous internal standard—clay mineral mixtures. Compaction of bulk shale material at 8000 psi in an hydraulic press produces preferred orientations comparable to that produced by smear or sedimentation. When used with a suitable platy internal standard which provides an estimate of clay mineral preferred orientation, excellent analytical precision is achieved routinely. Several lines of experimental evidence indicate that 1–5 µm MoS2 is an ideal orienting internal standard for use with compaction mounts.
Corrensite or ‘corrensite-like’ minerals occur in dike-intruded shales and siltstones of the Montana Group and Colorado Group (Early Cretaceous) in Western Montana. The < 1 μm size fraction of one specimen of this “corrensite-like” material has been studied in detail. X-ray diffraction data and chemical analysis indicate that this specimen is a regular or nearly regular interstratification of chlorite and dioctahedral smectite. Also described are other samples, which contain corrensite and additional phases. These samples were taken at several localities where basic dikes have intruded these shales and siltstones.
Background: There is no guideline for imaging post endovascular therapy (EVT). MRI is considered superior to noncontrast CT for assessment of final infarct volume and to distinguish contrast from hemorrhage. We sought to align the post EVT imaging practices with those after intravenous thrombolysis Methods: We reviewed the EMR records for all EVT patients from Jan 1, 2019 to Dec 31, 2021. We assessed quantity of CT within 24h of EVT, quantity of MRIs performed, and indications listed. We then undertook an educational program targeting stakeholders. The objective was to transition to MRI at 24h for imaging post EVT. Exceptions included neurologic change, need for antiplatelet infusion, or intraoperative complications. Results: Post intervention, a significant reduction in CT within 24h (-28%, P=0.01) and increase in MRIs (+42%, P<0.00). CT within 24h per patient dropped by 50% (1.12 pre vs 0.57 post). Radiation dose per patient dropped by 49%. Average imaging costs increased by 17%, and the number of transfers off unit for imaging increased by 11%. Good functional outcome dropped from 44% preintervention to 34% postintervention (P=0.06). Conclusions: This represents the first systematic evaluation of post EVT imaging in a single center. We demonstrate successful behavior changes for post EVT imaging.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
OBJECTIVES/GOALS: Clinical and Translational Science Award (CTSA) hubs are launching D&I Science cores to provide resources and services to promote the translation of clinical evidence into practice. We developed a D&I Science Core strategic plan reflecting our research community’s needs by assessing Implementation Science (IS) competencies. METHODS/STUDY POPULATION: The Tufts CTSI D&I Science Core was launched in early 2023. To design services that meet research community needs, we conducted a survey and key informant interviews based on Padek etal.’s list of Implementation Science (IS) competencies. The competencies are organized into four domains (Definition, Background, and Rationale; Theory and Approaches; Design & Analysis; and Practice-Based Considerations) and categorized by expertise level (beginner, intermediate, advanced). Participants who had attended or expressed interest in a D&I interest group were asked via an email survey to rate their level of confidence in completing selected IS-related research activities, about their experience with IS research or practice, and the types of resources, services and training they desired. RESULTS/ANTICIPATED RESULTS: Twenty researchers (20/65, 31%) submitted survey responses and six researchers participated in in-depth interviews. Survey respondents felt most confident in engaging stakeholders in IS research and least confident selecting a model or framework for a study. Results suggest that researcher capacity building is needed to: • Understand IS models and frameworks and their approaches, strengths, and limitations • Select and use models and frameworks in studies • Assemble IS teams and prepare grant proposals Suggestions for resources, services, and training, include: • Customized education to address diverse needs, knowledge levels, and learning styles • Promotion of D&I Core consultations and grant support services • Sharing of successful proposals to help researchers learn how to apply IS methods DISCUSSION/SIGNIFICANCE: A strategic workplan for the D&I Science Core was developed and implemented to address the findings. Initial emphasis is on developing easily accessible resources and timely consultations for investigators new to IS needing to apply these methods in current grant proposals, while also providing training resources for deeper skill building.