Incorporating paleontological data into phylogenetic inference can greatly enrich our understanding of evolutionary relationships by providing insights into the diversity and morphological evolution of a clade over geological timescales. Phylogenetic analysis of fossil data has been significantly aided by the introduction of the fossilized birth–death (FBD) process, a model that accounts for fossil sampling through time. A decade on from the first implementation of the FBD model, we explore its use in more than 170 empirical studies, summarizing insights gained through its application. We identify a number of challenges in applying the model in practice: it requires a working knowledge of paleontological data and their complex properties, Bayesian phylogenetics, and the mechanics of evolutionary models. To address some of these difficulties, we provide an introduction to the Bayesian phylogenetic framework, discuss important aspects of paleontological data, and finally describe the assumptions of the models used in paleobiology. We also present a number of exemplar empirical studies that have used the FBD model in different ways. Through this review, we aim to provide clarity on how paleontological data can best be used in phylogenetic inference. We hope to encourage communication between model developers and empirical researchers, with the ultimate goal of developing models that better reflect the data we have and the processes that generated them.

Objectives/Goals: To create, train, and evaluate the FAST-PACE (Promoting Academic and Community Engagement) Toolkit that catalyzes academic-community translation science teams during a public health emergency. The toolkit is a road map based on the Research Readiness and Partnership Protocol (R2P2), which was developed from the Flint Water Crisis. Methods/Study Population: A literature review was conducted by the Michigan Institute for Clinical & Health Research Community Engagement (MICHR CE) program and the Community-Based Organization Partners (CBOP), to identify important and common elements in disaster response protocols with a set of key interviews (n = 31) to glean perspectives from community leaders. Key findings were extracted and reviewed to generate guidelines and recommendations for the R2P2 protocol. The co-developed FAST-PACE Toolkit launched its expansion statewide to address emergencies and health disparities of communities in crisis. The iterative process consisted of community report-outs, gathering input from stakeholders, via discussion, and evaluation surveys. The feedback was used to develop, enhance, and tailor the toolkit and training content. Results/Anticipated Results: Data from training (n = 8) of the critical elements of the FAST-PACE Toolkit, which provides guidance for academic and community team members that includes 1) assessing community assets and needs; 2) engaging in clear and bidirectional communication; 3) facilitating transparency and equitable partnering; 4) identifying health equity and justice issues; and 5) conducting the evaluation of research. The training will be disseminated in-person and virtually across the state of Michigan resulting in participants sharing community-identified health issues and social determinants of health to assist MICHR CE to suggest resources to address health impacts. Discussion/Significance of Impact: The FAST-PACE Toolkit borne from the flint water crisis and confounded by other crises used CEnR principles to create a translation science roadmap. It equips communities and collaborating academic institutions across the state to respond to public health crises and fosters equitable translation science partnerships built on respect and trust.

Objectives/Goals: Substantial evidence supports the use of community engagement in CTS. Yet, there is a lack of empirical basis for recommending a particular level of community engagement over others. We aimed to identify associations between level of community involvement and study process outcomes, focusing on procedures to promote enrollment and inclusion. Methods/Study Population: Using manifest content analysis, we analyzed community engagement (CEn) strategies of studies indexed in ClinicalTrials.gov, focusing on studies 1) associated with 20 medical schools located in 8 southern states in the Black Belt, 2) conducted in 2015–2019, and 3) on 7 topics: cancer, depression, anxiety, hypertension, substance use disorder, cardiovascular disease, and HIV/AIDS. Data source was the ClinicalTrials.gov entry and publication for each study. We categorized each study on level of community involvement as described by the study protocol CTSA Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement continuum. Outcomes included recruitment and representativeness. Other codes included funder type, study phase, study status, and time to enrollment. Results/Anticipated Results: Of 890 studies that met inclusion criteria, only 493 had published findings. 286 studies (58%) met enrollment targets. Only 9 studies described any level of CEn (1 outreach, 3 consult, 1 involvement, 3 collaboration, and 1 shared leadership). Time to enrollment for these 9 studies (mean 28.78 mos.) was shorter than for studies without CEn (mean 37.43 months) (n.s.). CEn studies reached significantly higher enrollment (CEn mean  = 2395.11, non-CEn mean  = 463.93), p Discussion/Significance of Impact: Results demonstrate the substantial effect of CEn on enrollment and inclusion in clinical studies. However, the infinitesimal number of studies that reported CEn did not allow comparisons of level of engagement on the outcomes. Findings highlight ethical questions surrounding the lack of publishing incomplete studies.

Objectives/Goals: The aim of the study is to identify resistance factors for substance use (i.e., factors that explicitly help to avoid or reduce drug use). Identification of resistance factors could inform strategies that seek to reduce the prevalence of substance use and related disorders. Methods/Study Population: Adult twins aged 30–70 years were recruited from the Mid-Atlantic Twin Registry. A mixed-method approach, group concept mapping, was used to identify factors influencing participants to resist using substances. Approximately 155 participants produced 97 statements reflecting substance use resistance factors. Hierarchical cluster analysis and multidimensional scaling assessed how participants sorted and rated statements for their lifetime and current importance. Factor analysis was used to reduce data dimensionality. Reliability analyses were conducted to identify a subset of statements anticipated to consistently represent each cluster. Results were shared with participants to assess accuracy with their experiences. Results/Anticipated Results: Participants sorted 97 statements into 9 thematic clusters: (1) Controlling Personal, Negative Consequences; (2) Concern About Health and Well-being; (3) Lack of Desire; (4) Outside Influences; (5) Social Norms and My Reputation; (6) Career and Legal Impacts, (7) Avoiding Harm to Family and Relationships; (8) Preserving Family Relationships; and (9) Family and Friends Impact on Me. Participants consistently identified health concerns as an important substance use resistance factor. The statements will be further reduced to represent a smaller subset for future use as a scale to measure exposure to resistance factors. Discussion/Significance of Impact: Health concerns related to substance use were identified as an important resistance factor. This has been supported by research on smoking cessation and implemented in smoking prevention campaigns. Therefore, prioritizing health-related outcomes in prevention may be important to reduce substance use prevalence.

Jellyfishes have ecological and societal value, but our understanding of taxonomic identity of many jellyfish species remains limited. Here, an approach integrating morphological and molecular (16S ribosomal RNA and cytochrome oxidase I) data enables taxonomic assessment of the blubber jellyfish found in the Philippines. In this study, we aimed to resolve doubt on the taxonomy of Acromitoides purpurus, a valid binomen at the time of our research. Our morphological findings confirm that this jellyfish belongs to the genus Catostylus, and is distinct from known species of the genus inhabiting the Western Pacific, such as Catostylus ouwensi, Catostylus townsendi, and Catostylus mosaicus. Detailed morphological and molecular analyses of the type specimens from the Philippines with the other Catostylus species revive the binomen Catostylus purpurus and invalidate A. purpurus. Genetic analysis also distinguishes this Philippine jellyfish from C. townsendi and C. mosaicus. Through this study, we arranged several Catostylidae taxa into species inquirendae (Catostylus tripterus, Catostylus turgescens, and Acromitoides stiphropterus) and one genus inquirenda (Acromitoides) and provided an identification key for species of Catostylus. This comprehensive study confirms the blubber jellyfish as C. purpurus, enriching our understanding of jellyfish biodiversity. The integration of morphological and genetic analyses proves vital in resolving taxonomic ambiguities within the Catostylidae family and in the accurate identification of scyphozoan jellyfishes.

The global increase in observed forest dieback, characterized by the death of tree foliage, heralds widespread decline in forest ecosystems. This degradation causes significant changes to ecosystem services and functions, including habitat provision and carbon sequestration, which can be difficult to detect using traditional monitoring techniques, highlighting the need for large-scale and high-frequency monitoring. Contemporary developments in the instruments and methods to gather and process data at large scales mean this monitoring is now possible. In particular, the advancement of low-cost drone technology and deep learning on consumer-level hardware provide new opportunities. Here, we use an approach based on deep learning and vegetation indices to assess crown dieback from RGB aerial data without the need for expensive instrumentation such as LiDAR. We use an iterative approach to match crown footprints predicted by deep learning with field-based inventory data from a Mediterranean ecosystem exhibiting drought-induced dieback, and compare expert field-based crown dieback estimation with vegetation index-based estimates. We obtain high overall segmentation accuracy (mAP: 0.519) without the need for additional technical development of the underlying Mask R-CNN model, underscoring the potential of these approaches for non-expert use and proving their applicability to real-world conservation. We also find that color-coordinate based estimates of dieback correlate well with expert field-based estimation. Substituting ground truth for Mask R-CNN model predictions showed negligible impact on dieback estimates, indicating robustness. Our findings demonstrate the potential of automated data collection and processing, including the application of deep learning, to improve the coverage, speed, and cost of forest dieback monitoring.

Sepiolite and attapulgite have been found to be common, sometimes the major, clay minerals in calcareous lacustrine deposits on the southern High Plains in West Texas and eastern New Mexico. Deflation debris derived from the basins and calcareous soils developed in the debris and in the lacustrine deposits also often contain either or both minerals. Dolomite is the carbonate commonly associated with sepiolite and calcite has a similar relationship to attapulgite in the lacustrine deposits. Pedogenic formation of sepiolite and attapulgite appears unlikely in the area studied since an association with lacustrine materials was made in a very high percentage of the occurrences.

Sepiolite was found to be highly concentrated in the < 0•2μ fraction. A similar, but less pronounced, distribution was noted for attapulgite. The studies suggest that the minerals have developed authigenically in alkaline lacustrine environments during periods of desiccation. Such an environment, interrupted by more humid periods, would have obtained during dry Pleistocene intervals. Volcanic ash is suggested as the source of the essential silica. The Mg concentration would appear to determine whether sepiolite-dolomite or attapulgite-calcite were formed.

Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.

Geoarchaeological research as part of the AHRC funded Living with Monuments (LwM) project investigated the upper Kennet river system across the Avebury World Heritage landscape. The results demonstrate that in the early–mid-Holocene (c. 9500–1000 bc) there was very low erosion of disturbed soils into the floodplain, with floodplain deposits confined to a naturally forming bedload fluvial deposit aggrading in a shallow channel of inter-linked deeper pools. At the time of the Neolithic monument building in the 4th–early 3rd millennium bc, the river was wide and shallow with areas of presumed braid plain. Between c. 4000 and 1000 bc, a human induced signature of soil erosion became a minor component of fluvial sedimentation in the Kennet palaeo-channel but it was small scale and localised. This strongly suggests that there is little evidence of widespread woodland removal associated with Neolithic farming and monument building, despite the evidently large timber requirements for Neolithic sites like the West Kennet palisade enclosures. Consequently, there was relatively light human disturbance of the hinterland and valley slopes over the longue durée until the later Bronze Age/Early Iron Age, with a predominance of pasture over arable land. Rather than large Neolithic monument complexes being constructed within woodland clearings, representing ancestral and sacred spaces, the substantially much more open landscape provided a suitable landscape with areas of sarsen spreads potentially easily visible. During the period c. 3000–1000 bc, the sediment load within the channel slowly increased with alluvial deposition of increasingly humic silty clays across the valley floor. However, this only represents small-scale landscape disturbance. It is from the Late Bronze Age–Early Iron Age when the anthropogenic signal of human driven alluviation becomes dominant and overtakes the bedload fluvial signal across the floodplain, with localised colluvial deposits on the floodplain margins. Subsequently, the alluvial archive describes more extensive human impact across this landscape, including the disturbance of loessic-rich soils in the catchment. The deposition of floodplain wide alluvium continues throughout the Roman, medieval, and post-medieval periods, correlating with the development of a low-flow, single channel, with alluvial sediments describing a decreasing energy in the depositional environment.

Phylodynamic models can be used to estimate diversification trajectories from time-calibrated phylogenies. Here we apply two such models to phylogenies of non-avian dinosaurs, a clade whose evolutionary history has been widely debated. Although some authors have suggested that the clade experienced a decline in diversity, potentially starting millions of years before the end-Cretaceous mass extinction, others have suggested that the group remained highly diverse right up until the Cretaceous-Paleogene (K-Pg) boundary. Our results show that model assumptions, likely with respect to incomplete sampling, have a large impact on whether dinosaurs appear to have experienced a long-term decline or not. The results are also highly sensitive to the topology and branch lengths of the phylogeny used. Developing comprehensive models of sampling bias, and building larger and more accurate phylogenies, are likely to be necessary steps for us to determine whether dinosaur diversity was or was not in decline before the end-Cretaceous mass extinction.

OBJECTIVES/GOALS: Communities of color often report that their concerns are ignored and desire a means to facilitate effective community-academic engagement, especially during a crisis. The objective is to share lessons learned and challenges faced in the development of an online portal designed to meet this need. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) worked with community and academics to develop an online tool, the Michigan Research Engaging the Academy and Community in Health (M-REACH) platform. The community-engaged research (CEnR) project involved conducting qualitative interviews exploring connectivity to community and academic organizations and pilot testing of the novel platform. Following development, efforts were made to implement the statewide use of M-REACH. We will report on the challenges encountered and lessons learned from development and optimization of the platform. RESULTS/ANTICIPATED RESULTS: Authors will review the timeline of the launch of M-REACH. Steps to promote engagement of the locally developed platform to statewide utilization will be shared. Challenges encountered with scaling, matching the needs of differing communities both rural and urban, and navigating connections between remote geographies will be presented. Lessons learned and potential solutions will be discussed. DISCUSSION/SIGNIFICANCE: M-REACH can connect partners by increasing understanding of the CEnR process, enhancing alignment, and building a foundation for well-functioning research partnerships. Further work is required to address the challenges encountered in development and implementation.

Evidence from previous research suggests that frame-of-reference (FOR) training is effective at improving assessor ratings in many organizational settings. Yet no research has presented a thorough examination of systematic sources of variance (assessor-related effects, evaluation settings, and measurement design features) that might influence training effectiveness. Using a factorial ANOVA and variance components analyses on a database of four studies of frame-of-reference assessor training, we found that (a) training is most effective at identifying low levels of performance and (b) the setting of the training makes little difference with respect to training effectiveness. We also show evidence of the importance of rater training as a key determinant of the quality of performance ratings in general. Implications for FOR training theory and practice are discussed.

The sorption of the uranyl oxo-cation (UO22+)at different types of binding sites on layer silicate mineral surfaces was investigated. Well-characterized samples of vermiculite and hydrobiotite were exposed to aqueous uranyl under conditions designed to promote surface sorption either at fixed charge ionexchange sites or at amphoteric surface hydroxyl sites. The local structure of uranium in the sorption samples was directly measured using uranium L3-edge extended X-ray absorption fine structure (EXAFS). Polarized L1- and L3-edge X-ray absorption near-edge structure (XANES) measurements were used to characterize the orientation of uranyl groups in layered samples. X-ray diffraction (XRD) measurements of interlayer spacings were used to assess the effects of ion-exchange and dehydration upon the mineral structure. The most significant findings are: (1) Under conditions which greatly favor ion-exchange sorption mechanisms, uranyl retains a symmetric local structure suggestive of an outer-sphere complex, with a preferred orientation of the uranyl axis parallel to the mineral layers; (2) Upon dehydration, the ionexchange complexes adopt a less symmetric structure, consistent with an inner-sphere complex, with less pronounced orientation of the uranyl axis; and (3) For conditions which favor sorption at surface hydroxyl sites, uranyl has a highly distorted equatorial shell, indicative of stronger equatorial ligation, and the detection of a neighboring U atom suggests the formation of surface precipitates and/or oligomeric complexes.