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Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.
Aims
To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.
Method
A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.
Results
Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.
Conclusions
One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.
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.
Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.
Claims relating to foods’ nutrition content and potential health benefits have been shown to influence consumer preferences and purchases regardless of the nutritional quality of the product(1). In Australia, permitted claims include nutrition content claims, which refer to the presence or absence of a nutrient, and health claims, which refer to health benefits of foods or nutrients in a product. Health claims include general level health claims, which refer to normal processes and functions, and high level health claims, which refer to a disease or biomarker of a disease. Products that display a health claim must meet the Nutrient Profiling Scoring Criterion (NPSC), however this is not required for products to make a nutrition content claim. The aim of this study was to examine the use of nutrition content and health claims made on Australian ready meal products and assess the proportion of products displaying claims that meet the NPSC. Analysis of the ready meal category in the 2023 FoodSwitch database, a repository of Australian food packaging images and label data for over 28,000 foods developed by The George Institute for Global Health, was conducted(2,3). Foods in the ready meal category were identified and data from the nutrition information panel was collated to calculate whether they met the NPSC. Nutrition content and health claims were extracted from product images and categorised according to claim type (nutrition or health claim) and claimed nutrient or attribute. The proportion of products meeting the NPSC was then calculated overall and by claim type (nutrition content vs health claims). Data were available for 777 ready meal products. Of these, 682 (87.8%) met the NPSC. In total, 2051 nutrition content or health claims were identified across the ready meal products, with 1909 (93.1%) of these categorised as nutrition content claims. The remaining 142 claims identified were general level health claims, with no high level health claims identified. Almost all (n = 1857, 97.3%) nutrition content claims and all general level health claims were made on products which met the NPSC. The most common claims related to protein, energy and fibre content. The use of claims was prevalent across the ready meal food category in Australia, with claims relating to nutrient content being most common. While most claims were made on products that met the NPSC, there is a need for further research to ensure the NPSC appropriately distinguishes between healthy and less healthy food products. This will ensure consumers are equipped to make informed decisions when purchasing food products.
Anxiety and depression in epilepsy are common and impactful. Screening with validated measures at every epilepsy visit is a quality measure, yet screening remains limited due to time constraints.
Methods:
This study aimed to develop an implementation strategy for anxiety and depression screening at an epilepsy center and evaluate it in a pre-post design with RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Guided by the Capability, Opportunity, Motivation-Behavior behavior change wheel framework, the strategy incorporated electronic health record tools and support staff activation of electronic screeners during visit check-in. Outcomes were evaluated over five months post-implementation and compared with two 3-month pre-implementation timeframes.
Results:
Post-implementation, 29.2% of 943 visits met the anxiety and depression screening quality measure, a significant increase from 12.6% immediately pre-implementation (p < 0.0001) and 6.28% before any screening interventions (p < 0.0001). Patients who completed electronic screeners post-implementation were younger than non-completers (mean 39.3 vs. 43.4 years, p = 0.001) and more likely to be white than other race/ethnicity categories (p = 0.002). There was substantial variability in screening rates among clinic staff (0–80% for support staff, 10.1–55.3% for providers), with higher screening among neurology support staff than temporary staff. Only 0.23% of post-implementation visits had screeners initiated but left incomplete. A shift to virtual visits during COVID-19 complicated Maintenance.
Conclusions:
This framework-based implementation strategy effectively increased screening rates by epilepsy specialists, though challenges remain, including variability across clinic team members and lower reach among older and non-white patients. This study describes a feasible strategy for epilepsy centers to use for improved performance on an American Academy of Neurology quality measure (depression and anxiety screening for patients with epilepsy).
Jacobean visitation articles reveal increasing anxiety about preserving sacred space and material things from profane use. New churches and churchyards were consecrated by novel rites as sacred space was increasingly prioritised and emphasised in visitation. More and more prelates labelled the church building ‘the house of God’. By 1612, the archbishop of Canterbury's metropolitical visitation articles identified ecclesiastical space and furniture, notably the communion table, as ‘consecrated’ to God. English prelates widely adopted this sacralising rhetoric. These innovations originate not in the prescriptions of avant-garde prelates awaiting the advent of Laud but more commonly in those of Reformed conformist bishops.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Emerging societal expectations from biomedical research and intensifying international scientific competition are becoming existential matters. Based on a review of pertinent evidence, this article analyzes challenges and formulates public policy recommendations for improving productivity and impact of life sciences. Critical risks include widespread quality defects of research, particularly non-reproducible results, and narrow access to scientifically sound information giving advantage to health misinformation. In funding life sciences, the simultaneous shift to nondemocratic societies is an added challenge. Simply spending more on research will not be enough in the global competition. Considering the pacesetter role of the federal government, five national policy recommendations are put forward: (i) funding projects with comprehensive expectations of reproducibility; (ii) public–private partnerships for contemporaneous quality support in laboratories; (iii) making research institutions accountable for quality control; (iv) supporting new quality filtering standards for scientific journals and repositories, and (v) establishing a new network of centers for scientific health communications.
The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
We investigate air-entraining flows where degassing, rather than fragmentation, plays a significant role. Of interest is the power-law slope $\beta$ of the bulk bubble size distribution $N(a)$ during the air-generating period, when the total volume of bubbles is increasing. We study a canonical air-entraining flow created by strong underlying free-surface turbulence. We perform analysis using the population balance equation (PBE) and computations using direct numerical simulations (DNS) with bubble tracking. We quantify the importance of degassing by the ratio of degassing flux ($Q_D$) to entrainment flux ($Q_I$), $\mathcal {D}=Q_D/Q_I$, and the ratio of degassing rate ($\varLambda (a)$) to fragmentation rate ($\varOmega (a)$) for a bubble of radius $a$, $\varLambda (a)/\varOmega (a)$. For a broad range of large Froude numbers ${{Fr}}=U/\sqrt {L g}$, DNS give $\mathcal {D}=\operatorname {O}(1)$ (independent of ${{Fr}}$), showing that degassing is relevant, and $\varLambda (a) \gg \varOmega (a)$, showing that the bubble population is degassing-dominated. In contrast to fragmentation-dominated populations, such as those due to wave breaking, where $\beta =-10/3$, degassing-dominated populations have qualitatively different $N(a)$ during air entrainment. Analysis using the PBE shows that degassing-dominated $\beta$ is a function of $\varLambda (a)$, which has a turbulence-driven regime ($a< a_\varLambda$) and a buoyancy-driven regime ($a>a_\varLambda$). Here, $a_\varLambda$ is the bubble radius where terminal buoyant rise velocity equals $u_{rms}$. Consequently, $N(a)$ exhibits a split power with $\beta (a< a_\varLambda )=-4.\bar {3}$ and $\beta (a>a_\varLambda )=-5.8\bar {3}$ for moderate bubble Reynolds numbers ${{Re}}_b$. For large ${{Re}}_b$, $\beta (a>a_\varLambda )=-4.8\bar {3}$. The DNS strongly confirm these findings for moderate ${{Re}}_b$. By identifying and describing degassing-dominated bubble populations, this work contributes to the understanding and interpretation of broad types of air-entraining problems where degassing plays a relevant role.
Professor William Ivory (Ivor) Browne, consultant psychiatrist, who died on 24 January 2024, was a remarkable figure in the history of medicine in Ireland and had substantial influence on psychiatric practice and Irish society. Born in Dublin in 1929, Browne trained in England, Ireland, and the US. He was chief psychiatrist at St Brendan’s Hospital, Grangegorman, Dublin from 1965 to 1994 and professor of psychiatry at University College Dublin from 1967 to 1994. Browne pioneered novel and, at times, unorthodox treatments at St Brendan’s. Along with Dr Dermot Walsh, he led the dismantling of the old institution and the development of community mental health services during the 1970s and 1980s. He established the Irish Foundation for Human Development (1968–1979) and, in 1983, was appointed chairman of the group of European experts set up by the European Economic Community for reform of Greek psychiatry. After retirement in 1994, Browne practiced psychotherapy and pursued interests in stress management, living system theory, and how the brain processes trauma. For a doctor with senior positions in healthcare and academia, Browne was remarkably iconoclastic, unorthodox, and unafraid. Browne leaves many legacies. Most of all, Browne is strongly associated with the end of the era of the large ‘mental hospital’ at Grangegorman, a gargantuan task which he and others worked hard to achieve. This is his most profound legacy and, perhaps, the least tangible: the additional liberty enjoyed by thousands of people who avoided institutionalisation as a result of reforms which Browne came to represent.
Bacterial resistance is known to diminish the effectiveness of antibiotics for treatment of urinary tract infections. Review of recent healthcare and antibiotic exposures, as well as prior culture results is recommended to aid in selection of empirical treatment. However, the optimal approach for assessing these data is unclear. We utilized data from the Veterans Health Administration to evaluate relationships between culture and treatment history and the subsequent probability of antibiotic-resistant bacteria identified in urine cultures to further guide clinicians in understanding these risk factors.
Methods:
Using the XGBoost algorithm, a retrospective cohort of outpatients with urine culture results and antibiotic prescriptions from 2017 to 2022 was used to develop models for predicting antibiotic resistance for three classes of antibiotics: cephalosporins, fluoroquinolones, and trimethoprim/sulfamethoxazole (TMP/SMX) obtained from urine cultures. Model performance was assessed using Area Under the Receiver Operating Characteristic curve (AUC) and Precision-Recall AUC (PRAUC)
Results:
There were 392,647 prior urine cultures identified in 214,656 patients. A history of bacterial resistance to the specific treatment was the most important predictor of subsequent resistance for positive cultures, followed by a history of specific antibiotic exposure. The models performed better than previously established risk factors alone, especially for fluoroquinolone resistance, with an AUC of .84 and PRAUC of .70. Notably, the models’ performance improved markedly (AUC = .90, PRAUC = .87) when applied to cultures from patients with a known history of resistance to any of the antibiotic classes.
Conclusion:
These predictive models demonstrate potential in guiding antibiotic prescription and improving infection management.
Background: The fragility index (FI) is the minimum number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result to a non-significant result. We used this to measure the robustness of trials comparing carotid endarterectomy (CEA) to carotid artery stenting (CAS). Methods: A search was conducted in MEDLINE, Embase, and PubMed on RCTs comparing CEA to CAS. The trials need to have statistically significant results and dichotomous primary endpoints to be included. Results: Our literature search identified 10 RCTs which included 9382 patients (4734 CEA, 4648 CAS). The primary end points of all included trials favoured CEA over CAS. The median FI was 9.5 (interquartile range 2.25 - 21.25). All of the studies that reported lost-to-follow-up (LTFU) had LTFU greater than its fragility index, which raises concern that the missing data could change the results of the trial from statistically significant to statistically insignificant. Conclusions: A small number of events (FI, median 9.5) were required to render the results of carotid artery stenosis RCTs comparing CEA to CAS statistically insignificant. All of the studies that reported LTFU had LTFU greater than its fragility index.
The centrifugal mirror confinement scheme incorporates supersonic rotation of a plasma into a magnetic mirror device. This concept has been shown experimentally to drastically decrease parallel losses and increase plasma stability as compared with prior axisymmetric mirrors. MCTrans++ is a dimensionless (0-D) scoping tool which rapidly models experimental operating points in the Centrifugal Mirror Fusion Experiment (CMFX) at the University of Maryland. In the low-collisionality regime, parallel losses can be modelled analytically. A confining potential is set up that is partially ambipolar and partially centrifugal. Due to the stabilizing effects of flow shear, the perpendicular losses can be modelled as classical. Radiation losses such as bremsstrahlung and cyclotron emission are taken into account. A neutrals model is included, and, in some circumstances, charge-exchange losses are found to exceed all other loss mechanisms. We use the SUNDIALS ARKODE library to solve the underlying equations of this model; the resulting software is suitable for scanning large parameter spaces, and can also be used to model time-dependent phenomena such as a capacitive discharge. MCTrans++ has been used to verify results from prior centrifugal mirrors, create an experimental plan for CMFX and find configurations for future reactor-scale fusion devices.
Maternal pre-pregnancy body mass index is positively associated with offspring obesity, even at adulthood, whereas breastfeeding decreases the risk of obesity. The present study was aimed at assessing whether breastfeeding moderates the association of maternal pre-pregnancy body mass index with offspring body composition at adulthood, using data from 3439 subjects enrolled in a southern Brazilian birth cohort. At 30 years of age, maternal pre-pregnancy body mass index was positively associated with offspring prevalence of obesity, abdominal obesity, as well as body mass index and fat and lean mass index. Breastfeeding moderated the association of maternal pre-pregnancy obesity with offspring adiposity at 30 years of age. For those breastfed<6 months, body mass index was 4.13 kg/m2 (95% confidence interval: 2.98; 5.28) higher among offspring of obese mothers, in relation to offspring of normal weight mothers, whereas among those breastfed≥6 months the magnitude of the difference was small [2.95 kg/m2 (95% confidence interval: 1.17; 4.73)], p-value for interaction = 0.03. Concerning obesity, among those who had been breastfed < 6 months, the prevalence of obesity was 2.56 (95% confidence interval: 1.98; 3.31) times higher among offspring of obese mothers. On the other hand, among those who were breastfed ≥ 6 months, the prevalence of obesity was 1.82 (95% confidence interval: 1.09; 3.04) times higher among offspring of obese mothers. Therefore, among overweight mothers breastfeeding for more than 6 months should be supported, as it may mitigate the consequences of maternal overweight on offspring body composition.
Background: Basilar fenestration is a rare congenital anomaly. When present, it is commonly found at the proximal portion of the artery near the vertebrobasilar junction. Methods: This is a case report of a ruptured basilar fenestration aneurysm in a 47-year-male successfully treated with endovascular coiling. Results: A 47-year-old male presented with sudden onset headache, neck pain, blurry vision, nausea, vomiting, and diaphoresis. Cerebral angiogram revealed a saccular basilar fenestration aneurysm located at the vertebrobasilar junction measuring 3.1 x 2.6 x 3.4 mm with a 2.3 mm neck. Multiple coils were placed including Target 360 Nano 2mm x 4 cm (Stryker, Kalamazoo, MI, US), Target 360 Nano 1.5 mm x 2 cm (Stryker, Kalamazoo, MI, US), and Target Helical Nano 1.5 mm x 1 cm (Stryker, Kalamazoo, MI, US). A repeat angiogram revealed complete exclusion of the aneurysm with preservation of both vertebral arteries. Conclusions: A literature review was conducted on basilar fenestration aneurysms which included 158 patients from 39 studies. Overall, complete exclusion of the aneurysm was achieved in 75.8% of cases, with 22.4% of cases having residual flow and 1.8% of cases with unreported exclusion status.
We investigate the fundamental time scales that characterise the statistics of fragmentation under homogeneous isotropic turbulence for air–water bubbly flows at moderate to large bubble Weber numbers, $We$. We elucidate three time scales: $\tau _r$, the characteristic age of bubbles when their subsequent statistics become stationary; $\tau _\ell$, the expected lifetime of a bubble before further fragmentation; and $\tau _c$, the expected time for the air within a bubble to reach the Hinze scale, radius $a_H$, through the fragmentation cascade. The time scale $\tau _\ell$ is important to the population balance equation (PBE), $\tau _r$ is critical to evaluating the applicability of the PBE no-hysteresis assumption, and $\tau _c$ provides the characteristic time for fragmentation cascades to equilibrate. By identifying a non-dimensionalised average speed $\bar {s}$ at which air moves through the cascade, we derive $\tau _c=C_\tau \varepsilon ^{-1/3} a^{2/3} (1-(a_{max}/a_H)^{-2/3})$, where $C_\tau =1/\bar {s}$ and $a_{max}$ is the largest bubble radius in the cascade. While $\bar {s}$ is a function of PBE fragmentation statistics, which depend on the measurement interval $T$, $\bar {s}$ itself is independent of $T$ for $\tau _r \ll T \ll \tau _c$. We verify the $T$-independence of $\bar {s}$ and its direct relationship to $\tau _c$ using Monte Carlo simulations. We perform direct numerical simulations (DNS) at moderate to large bubble Weber numbers, $We$, to measure fragmentation statistics over a range of $T$. We establish that non-stationary effects decay exponentially with $T$, independent of $We$, and provide $\tau _r=C_{r} \varepsilon ^{-1/3} a^{2/3}$ with $C_{r}\approx 0.11$. This gives $\tau _r\ll \tau _\ell$, validating the PBE no-hysteresis assumption. From DNS, we measure $\bar {s}$ and find that for large Weber numbers ($We>30$), $C_{\tau }\approx 9$. In addition to providing $\tau _c$, this obtains a new constraint on fragmentation models for PBE.
OBJECTIVES/GOALS: As hospitals across the nation respond to the need to address community violence, there is a dearth of Hospital-based Violence Intervention Programs (HVIPs) in the South despite having disproportionate rates. This research aims to identify key factors and strategies for implementation of an HVIP among rural patient populations in a southern state. METHODS/STUDY POPULATION: Semi-structured interviews will be conducted with medical providers, social service organizations, and patients transferred from four high-risk rural areas in Arkansas. Data will be analyzed using Framework Analysis, a rapid analysis approach involving framework development, code application, impactful statement identification, and content analysis. Evidence- Based Quality Improvement (EBQI), a group consensus making process, will be conducted to identify key implementation strategies and factors to adapt based interview findings. Priority areas for adaptation will be identified via systematic rating. The EBQI team, including researchers and key rural stakeholders will engage in a series of discussion, vote on final strategies, and develop a guide for future HVIP implementation and pilot testing. RESULTS/ANTICIPATED RESULTS: Findings from this study will result in a prioritized list of barriers and facilitators across sample groups. Factors will be rated by level of importance. Cluster maps will display the relationships among factors. Go and no-go zones will be identified based on importance and feasibility. Implementation strategies will be mapped to barriers and facilitators. DISCUSSION/SIGNIFICANCE: The findings will result in a culturally and geographically relevant HVIP model and package of implementation strategies to test in future hybrid trials (feasibility pilot & multi-site RCT); and shape the future of violence prevention efforts in healthcare settings across the rural South.