Precision or “Personalized Medicine” and “Big Data” are growing trends in the biomedical research community and highlight an increased focus on access to larger datasets to effectively explore disease processes at the molecular level versus the previously common one-size-fits all approach. This focus necessitated a local transition from independent lab and siloed projects to a single software application utilizing a common ontology to create access to data from multiple repositories. Use of a common system has allowed for increased ease of collaboration and access to quality biospecimens that are extensively annotated with clinical, molecular, and patient associated data. The software needed to function at an enterprise level while continuing to allow investigators the autonomy and security access they desire. To identify a solution, a working group comprised of representation from independent repositories and areas of research focus across departments was established and responsible for review and implementation of an enterprise-wide biospecimen management system. Central to this process was the creation of a unified vocabulary across all repositories, including consensus around source of truth, standardized field definitions, and shared terminology.

There is a scarcity of psychological interventions for self-harm in young people, either developed or adapted for use in low and middle-income countries (LMICs). ATMAN is a psychological intervention developed in India for youth with three key modules: problem-solving, emotion regulation and social network strengthening skills in addition to crisis management. ATMAN was delivered in 27 youth with a history of self-harm (14–24 years old) sequentially by a specialist and it a non-specialist counsellor. Out of 27, 18 youth who started the ATMAN intervention completed it, and 13 completed the 10-month follow-up. There was a significant reduction in post-intervention scores on Beck’s Scale for Suicidal Ideation (BSI) (mean difference [confidence interval]: 14.1 [17.2, 10.9]) and Patient Health Questionnaire (PHQ-9) (9.6 [12.8, 6.4]) from the baseline scores, irrespective of who delivered the intervention (non-specialist vs. specialist). The difference remained significant at the 10-month follow-up (BSI: 17.0 [20.5, 13.6] and PHQ-9: 10.5 [14.5, 6.6]). Themes such as improved understanding of self-harm acting as a deterrent, using ATMAN strategies to deal with daily life distress, and the importance of addressing stigma in self-harm emerged during the qualitative interviews. Although requiring further evaluation, ATMAN shows promise as a scalable intervention that can be used in LMICs to reduce the burden of suicide in young people.

The aim of this study was to determine whether there was a significant change in cardiac [123I]-metaiodobenzylguanidine uptake between baseline and follow-up in individuals with mild cognitive impairment with Lewy bodies (MCI-LB) who had normal baseline scans. Eight participants with a diagnosis of probable MCI-LB and a normal baseline scan consented to a follow-up scan between 2 and 4 years after baseline. All eight repeat scans remained normal; however, in three cases uptake decreased by more than 10%. The mean change in uptake between baseline and repeat was −5.2% (range: −23.8% to +7.0%). The interpolated mean annual change in uptake was −1.6%.

We perform direct numerical simulations of soluble bubbles dissolving in a Taylor–Couette (TC) flow reactor with a radius ratio of $\eta =0.5$ and Reynolds number in the range $0 \leq Re \leq 5000$, which covers the main regimes of this flow configuration, up to fully turbulent Taylor vortex flow. The numerical method is based on a geometric volume-of-fluid framework for incompressible flows coupled with a phase-change solver that ensures mass conservation of the soluble species, whilst boundary conditions on solid walls are enforced through an embedded boundary approach. The numerical framework is validated extensively against single-phase TC flows and competing mass transfer in multicomponent mixtures for an idealised infinite cylinder and for a bubble rising in a quiescent liquid. Our results show that when bubbles in a TC flow are mainly driven by buoyancy, theoretical formulae derived for spherical interfaces on a vertical trajectory still provide the right fundamental relationship between the bubble Reynolds and Sherwood numbers, which reduces to $Sh \propto \sqrt {Pe}$ for large Péclet values. For bubbles mainly transported by TC flows, the dissolution of bubbles depend on the TC Reynolds number and, for the turbulent configurations, we show that the smallest characteristic turbulent scales control mass transfer, in agreement with the small-eddy model of Lamont & Scott (AIChE J., vol. 16, 1970, pp. 513–519). Finally, the interaction between two aligned bubbles is investigated and we show that a significant increase in mass transfer can be obtained when the rotor of the apparatus is operated at larger speeds.

This article proposes a framework of linked software agents that continuously interact with an underlying knowledge graph to automatically assess the impacts of potential flooding events. It builds on the idea of connected digital twins based on the World Avatar dynamic knowledge graph to create a semantically rich asset of data, knowledge, and computational capabilities accessible to humans, applications, and artificial intelligence. We develop three new ontologies to describe and link environmental measurements and their respective reporting stations, flood events, and their potential impact on population and built infrastructure as well as the built environment of a city itself. These coupled ontologies are deployed to dynamically instantiate near real-time data from multiple fragmented sources into the World Avatar. Sequences of autonomous agents connected via the derived information framework automatically assess consequences of newly instantiated data, such as newly raised flood warnings, and cascade respective updates through the graph to ensure up-to-date insights into the number of people and building stock value at risk. Although we showcase the strength of this technology in the context of flooding, our findings suggest that this system-of-systems approach is a promising solution to build holistic digital twins for various other contexts and use cases to support truly interoperable and smart cities.

Inhibitory control plays an important role in children’s cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents’ psychopathology are associated with children’s inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children’s behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; Mage = 7.13 years; Rangeage = 4–11 years). Results showed that theta power, which was positively predicted by prenatal SES and was negatively related to children’s externalizing problems, mediated the longitudinal and negative relation between them. ERP amplitudes and latencies did not mediate the longitudinal association between prenatal risk factors (i.e., prenatal SES and maternal psychopathology) and children’s internalizing and externalizing problems. Our findings increase our understanding of the neural pathways linking early risk factors to children’s psychopathology.

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.

Biodesign is a relatively new interdisciplinary field, which has grown rapidly over the last decade (as evidenced for example by the growth in student teams entering the Biodesign Challenge from 9 in 2016 to 52 in 2024).

The surface microtopography of hematite over the course of dissolution in oxalic and citric acids was examined by in-situ and ex-situ atomic-force microscopy. In-situ imaging of the basal-plane surface of a centimeter-scale natural hematite sample immersed in 2 mM citric acid demonstrated that the basal-plane surface was relatively unreactive; rather, dissolution occurred along step edges and via etch-pit formation. Ex-situ imaging of synthetic hematite particles following batch dissolution in 1 mM oxalic acid showed similar dissolution features on basal-plane surfaces; in addition, etching along particle edges was apparent. The presence of etch features is consistent with a surface-controlled dissolution reaction. The results are in agreement with previous investigations suggesting that the basal-plane surface is relatively unreactive with respect to ligand exchange. Both in-situ and ex-situ imaging of particle surfaces can provide valuable information on the roles of surface structures and microtopographic features in mineral dissolution.

Access to safe drinking water is among the most important determinants of public health outcomes. We pair household-level data from Iraq together with data on armed conflict and adopt a generalized difference-in-differences approach to study the relationship between household drinking water sources and armed conflict intensity. We find that households located in conflict-affected areas are more likely to use piped water accessed at their homes or bottled water as their primary source of drinking water, but are less likely to use public water sources or tanked water delivered on trucks and carts. We explore the temporal dynamics of these adjustments as well as heterogeneity by household characteristics. We further present direct evidence that conflict-exposed households are less likely to travel to obtain water.

Automatic dialog systems have become a mainstream part of online customer service. Many such systems are built, maintained, and improved by customer service specialists, rather than dialog systems engineers and computer programmers. As conversations between people and machines become commonplace, it is critical to understand what is working, what is not, and what actions can be taken to reduce the frequency of inappropriate system responses. These analyses and recommendations need to be presented in terms that directly reflect the user experience rather than the internal dialog processing.

This paper introduces and explains the use of Actionable Conversational Quality Indicators (ACQIs), which are used both to recognize parts of dialogs that can be improved and to recommend how to improve them. This combines benefits of previous approaches, some of which have focused on producing dialog quality scoring while others have sought to categorize the types of errors the dialog system is making. We demonstrate the effectiveness of using ACQIs on LivePerson internal dialog systems used in commercial customer service applications and on the publicly available LEGOv2 conversational dataset. We report on the annotation and analysis of conversational datasets showing which ACQIs are important to fix in various situations.

The annotated datasets are then used to build a predictive model which uses a turn-based vector embedding of the message texts and achieves a 79% weighted average f1-measure at the task of finding the correct ACQI for a given conversation. We predict that if such a model worked perfectly, the range of potential improvement actions a bot-builder must consider at each turn could be reduced by an average of 81%.