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This study reports on a set of experiments designed to clarify the impact of the rotational transform on confinement quality at the TJ-II stellarator. For this purpose, the net plasma current is controlled using external coils, resulting in the modification of the rotational transform profile. Significant and systematic variations of the edge electron density gradients (up to $50\,\%{-}60\,\%$) and the plasma energy content ($20\,\%{-}30\,\%$) are achieved. The explanation of this behaviour relies on the placement of low-order rational surfaces in relation to the edge gradient region, which affect local turbulence fluctuation levels, facilitating the formation of zonal flows and concomitant transport barriers. This hypothesis is confirmed experimentally on the basis of a broad array of diagnostic measurements. Calculations based on a resistive magnetohydrodynamic turbulence model provide qualitative support for this hypothesis, clarifying the impact on confinement of specific rational surfaces and highlighting the complex nature of magnetically confined fusion plasmas.
Often in Software Engineering, a modeling formalism has to support scenarios of inconsistency in which several requirements either reinforce or contradict each other. Paraconsistent transition systems are proposed in this paper as one such formalism: states evolve through two accessibility relations capturing weighted evidence of a transition or its absence, respectively. Their weights come, parametrically, from a residuated lattice. This paper explores both i) a category of these systems, and the corresponding compositional operators and ii) a modal logic to reason upon them. Furthermore, two notions of crisp and graded simulation and bisimulation are introduced in order to relate two paraconsistent transition systems. Finally, results of modal invariance, for specific subsets of formulas, are discussed.
Quantifying and assessing the computational accuracy of coarse-graining simulations of turbulence is challenging and imperative to achieve prediction – computations and results with a quantified and adequate degree of uncertainty that can be confidently used in projects without reference data. Verification, validation, and uncertainty quantification (VVUQ) provide the tools and metrics to accomplish such an objective. This chapter reviews these methods and illustrates their importance to coarse-graining models. Toward this end, we first describe the sources of computational errors and uncertainties in coarse-graining simulations of turbulence, followed by the concepts of VVUQ. Next, we utilize the modified equation analysis and the physical interpretation of a complex problem to demonstrate the role of VVUQ in evaluating and enhancing the fidelity and confidence in numerical simulations. This is crucial to achieving predictive rather than postdictive simulations.
Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.
Methods
This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.
Results
When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.
Limitations
This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.
Conclusions
These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
Good social connections are proposed to positively influence the course of cognitive decline by stimulating cognitive reserve and buffering harmful stress-related health effects. Prior meta-analytic research has uncovered links between social connections and the risk of poor health outcomes such as mild cognitive impairment, dementia, and mortality. These studies have primarily used aggregate data from North America and Europe with limited markers of social connections. Further research is required to explore these associations longitudinally across a wider range of social connection markers in a global setting.
Research Objective:
We examined the associations between social connection structure, function, and quality and the risk of our primary outcomes (mild cognitive impairment, dementia, and mortality).
Method:
Individual participant-level data were obtained from 13 longitudinal studies of ageing from across the globe. We conducted survival analysis using Cox regression models and combined estimates from each study using two-stage meta-analysis. We examined three social constructs: connection structure (living situation, relationship status, interactions with friends/family, community group engagement), function (social support, having a confidante) and quality (relationship satisfaction, loneliness) in relation to the risks of three primary outcomes (mild cognitive impairment, dementia, and mortality). In our partially adjusted models, we included age, sex, and education and in fully adjusted models used these variables as well as diabetes, hypertension, smoking, cardiovascular risk, and depression.
Preliminary results of the ongoing study:
In our fully adjusted models we observed: a lower risk of mild cognitive impairment was associated with being married/in a relationship (vs. being single), weekly community group engagement (vs. no engagement), weekly family/friend interactions (vs. not interacting), and never feeling lonely (vs. often feeling lonely); a lower risk of dementia was associated with monthly/weekly family/friend interactions and having a confidante (vs. no confidante); a lower risk of mortality was associated with living with others (vs. living alone), yearly/monthly/weekly community group engagement, and having a confidante.
Conclusion:
Good social connection structure, function, and quality are associated with reduced risk of incident MCI, dementia, and mortality. Our results provide actionable evidence that social connections are required for healthy ageing.
Different starch-to-protein ratios were compared among neutered and spayed domiciled cats. Male and female obese and non-obese cats were fed kibble diets ad libitum for 4 months high in starch (HS (38 % crude protein (CP)): starch 32 %, protein 38 %; DM basis) or high in protein (HP (55 % CP): starch 19 %, protein 55 %) but similar in energy and fat in a crossover design. Physical activity was evaluated using an accelerometer, and body composition (BC), energy expenditure (EE) and water turnover (WT) using the doubly labelled water method. Results were compared in a 2 diet × 2 sex × 2 body condition factorial arrangement. Cats fed the HS (38 % CP) diet maintained a constant body weight, but lean mass (LM) tended to be reduced in female obese but to be increased in male non-obese (P < 0·08) and increased in female non-obese cats (P = 0·01). The HP (55 % CP) diet induced an increase in cat body weight and LM (P < 0·05) without altering BC proportion. EE tended to be higher in males (351 (se 8) kJ/kg0·67/d) than females (330 (se 8) kJ/kg0·67/d; P = 0·06), was unaffected by diet or BC, decreased as age increased (R2 0·44; P < 0·01) and increased as physical activity increased (R2 0·58; P < 0·01). WT was higher for the HP (55 % CP) diet (P < 0·01) and increased with EE (R2 0·65; P < 0·01). The HS (38 % CP) diet favoured body weight control during 4 months of ad libitum feeding. Caution is necessary to balance protein in diets of female obese cats over 5 years, as they may have low energy and food intake, with LM loss.
The COVID-19 pandemic has affected the continuity of cognitive rehabilitation (CR) worldwide. However, the use of teleneuropsychology (TNP) to provide CR has contributed significantly to the continuity of treatment. The objective of this study was to measure the effects of CR via the TNP on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with Mild Cognitive Impairment (MCI).
Participants and Methods:
A sample of 60 patients (60% female; age: 72.4±6.96) with MCI according to Petersen criteria was randomly divided into two groups: 30 cases (treatment group) and 30 controls (waiting list group). Subjects were matched for age, sex, and MMSE or MoCA.
The treatment group received ten weekly CR sessions of 45 minutes weekly. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different Linear Mixed Models were estimated to test treatment effect (CR vs. Controls) on each outcome of interest over Time (Pre/Post), controlling for Diagnosis, Age, Sex, and MMSE/MoCA performance.
Results:
A significant Group (Control/Treatment) x Time (pre/post) interaction revealed that the treatment group at 10 weeks had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency(p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ Satisfaction p=0.004) and use of memory strategies (MMQ Strategy p=0.00), and a significant reduction of affective symptomatology: depression (GDS p=0.00), neuropsychiatric symptoms (NPIQ p=0.045), Forgetfulness (EDO-10 p=0.00), Stress (DAS Stress p=0.00).
Conclusions:
This is the first study to test CR using teleNP in South America. Our results suggest that CR through teleNP is an effective intervention to improve performance on cognitive variables and reduce neuropsychiatric symptomatology compared to patients with MCI. These results have great significance in the context of the COVID-19 pandemic in South America, where teleNP is proving to be a valuable tool.
Singapore imports more than 90 per cent of its daily food consumption. Imports are one of the four key “taps” on the supply side for meeting demand. The other three include domestic production, reserves and growing food overseas and re-importing it into the country. Within the island citystate, rice plays a crucial role, since it is a staple in the Singaporean diet. According to the country's 2010 National Nutrition Survey, rice and rice alternatives (e.g., wheat) composed the largest share of consumption requirements (44 per cent), followed by meat and meat alternatives (30 per cent), fruits (12 per cent), vegetables (12 per cent) and wholegrains (2 per cent) (HPB 2010). Despite rice's importance, Singapore relies purely on international sources to meet rice consumption requirements. This is because rice is a land-extensive commodity, requiring vast expanses of land that the city-state lacks.
The COVID-19 outbreak was declared a pandemic by the World Health Organization in March 2020, and it has been a significant disruptor to global health, with more than 450 million cases recorded as of March 2022. It has also disrupted the global economy, causing economic contractions that have not been seen since the Great Depression of the 1930s. This chapter presents policy insights for Singapore's food security in the face of COVID-19, learning from its experience in its rice sector. It is divided into three sections. The first section describes the policy context for food security in Singapore prior to COVID-19, describing the evolution of Singapore's approaches, including the investments in domestic production after the Global Food Price Crisis of 2007–8; the development of its Food Security Roadmap in 2013; the restructuring of its food authority, the Agri-Veterinary Authority and its transformation into the Singapore Food Authority announced in 2018; and the launching in 2019 of the “30-by-30” target of 30 per cent food self-sufficiency by 2030. This section highlights that across these transitions, Singapore has forgone attempts to boost domestic production and stayed the course of import reliance for rice, by focusing on diversifying foreign sources for rice, as well as other commodities.
OBJECTIVES/GOALS: Surgical training is constrained by duty hour limits, bias, and a trial-and-error learning process. Surgeon skill variation is a healthcare system disparity that can impact patient outcomes. Incorporating validated, standardized assessment tools and machine learning (ML) algorithms may help to standardize and reduce bias in surgeon education. METHODS/STUDY POPULATION: To support assessment tool and ML algorithm development, we are curating an annotated video registry of neurosurgical procedures. Point-of-view video of resident and attending neurosurgeons performing craniotomies is recorded via an eye-tracking headset. A Delphi panel of neurosurgeons will review the video and determine which represent expert versus trainee performance. Neurosurgery attendings will be interviewed to provide descriptions of craniotomies which will be used to develop an assessment rubric. A Delphi panel will determine what rubric components should be maintained. New craniotomy videos will be viewed by attendings in a blinded fashion while completing the assessment rubric. An online feedback platform is being developed allowing residents to prospectively track assessment data. RESULTS/ANTICIPATED RESULTS: We anticipate development of an annotated, institutional video database featuring craniotomies performed by residents and attending neurosurgeons. Using a Delphi approach, we anticipate achieving consensus on which videos reflect expert versus trainee performance. We anticipate development of a novel craniotomy assessment rubric that is both valid and reliable. Our online feedback platform will allow prospective tracking of assessment data from multiple sources and enhanced transparency in the feedback process. The video registry and assessment data will enable development of novel ML algorithms able to recognize craniotomy segments and estimate operator skill. DISCUSSION/SIGNIFICANCE: Building a video registry of procedures, validated assessment tools, and a prototype feedback platform enables a pipeline for ML algorithm development. Together these tools will help to standardize and optimize resident education translating to earlier operative independence, improved patient safety, and reduced bias during surgical training.
Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.
Methods
After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.
Results
The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.
Conclusions
These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.
Here we report a quantitative analysis of human metaphase II (MII) oocytes from a 22-year-old oocyte donor, retrieved after ovarian-controlled hyperstimulation. Five surplus donor oocytes were processed for transmission electron microscopy (TEM), and a stereological analysis was used to quantify the distribution of organelles, using the point-counting technique with an adequate stereological grid. Comparisons between means of the relative volumes (Vv) occupied by organelles in the three oocyte regions, cortex (C), subcortex (SC) and inner cytoplasm (IC), followed the Kruskal–Wallis test and Mann–Whitney U-test with Bonferroni correction. Life cell imaging and TEM analysis confirmed donor oocyte nuclear maturity. Results showed that the most abundant organelles were smooth endoplasmic reticulum (SER) elements (26.8%) and mitochondria (5.49%). Significant differences between oocyte regions were found for lysosomes (P = 0.003), cortical vesicles (P = 0.002) and large SER vesicles (P = 0.009). These results were quantitatively compared with previous results using prophase I (GV) and metaphase I (MI) immature oocytes. In donor MII oocytes there was a normal presence of cortical vesicles, SER tubules, SER small, medium and large vesicles, lysosomes and mitochondria. However, donor MII oocytes displayed signs of cytoplasmic immaturity, namely the presence of dictyosomes, present in GV oocytes and rare in MI oocytes, of SER very large vesicles, characteristic of GV oocytes, and the rarity of SER tubular aggregates. Results therefore indicate that the criterion of nuclear maturity used for donor oocyte selection does not always correspond to cytoplasmic maturity, which can partially explain implantation failures with the use of donor oocytes.
This study uses luminescence and 14C accelerator mass spectrometry procedures to date relevant glaciofluvial and glacial deposits from the south-central and southeastern Pyrenees (Andorra–France–Spain). We distinguish two types of end-moraine complexes: (1) those in which at least a far-flung moraine exists beyond a frequently nested end-moraine complex (the most common) and (2) those in which a close-nested end moraine encompasses at least two glacial cycles. Both types formed within six distinctive glacial intervals: (1) A penultimate glacial cycle during Marine Oxygen Isotope Stage (MIS) 6 and older glaciofluvial terraces occurred beyond the range of the luminescence dating method. (2) An early glacial advance in MIS 5d (~97 −15/+19 ka) was followed by glacial retreat during MIS 5c (< 91 ± 9 ka). (3) The last maximum ice extent (LMIE) was in early MIS 4 (~74 ± 4.5 ka). (4) Unexpectedly, glaciers thinned during the second half of MIS 3 (~39 −6/+11 ka). (5) During the MIS 3–2 transition, glaciers subsequently fluctuated behind the LMIE limits. (6) The global last glacial maximum (LGM) started as early as ~26.6 ± 0.365 ka b2k, and the corresponding end moraines were built behind the LMIE limits or merged with it, forming close-nested moraines.
Pain following surgery for cardiac disease is ubiquitous, and optimal management is important. Despite this, there is large practice variation. To address this, the Paediatric Acute Care Cardiology Collaborative undertook the effort to create this clinical practice guideline.
Methods:
A panel of experts consisting of paediatric cardiologists, advanced practice practitioners, pharmacists, a paediatric cardiothoracic surgeon, and a paediatric cardiac anaesthesiologist was convened. The literature was searched for relevant articles and Collaborative sites submitted centre-specific protocols for postoperative pain management. Using the modified Delphi technique, recommendations were generated and put through iterative Delphi rounds to achieve consensus
Results:
60 recommendations achieved consensus and are included in this guideline. They address guideline use, pain assessment, general considerations, preoperative considerations, intraoperative considerations, regional anaesthesia, opioids, opioid-sparing, non-opioid medications, non-pharmaceutical pain management, and discharge considerations.
Conclusions:
Postoperative pain among children following cardiac surgery is currently an area of significant practice variability despite a large body of literature and the presence of centre-specific protocols. Central to the recommendations included in this guideline is the concept that ideal pain management begins with preoperative counselling and continues through to patient discharge. Overall, the quality of evidence supporting recommendations is low. There is ongoing need for research in this area, particularly in paediatric populations.
Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement.
Methods
Children and adolescents aged 6–17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses.
Results
Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control.
Conclusions
Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.
The Brazilian Cerrado, a Neotropical savanna, is a fire-prone ecosystem where the ground layer biomass consists mainly of graminoids. However, as for other savannas, the effects of fire cues (such as smoke) on Cerrado grasses do not present a clear pattern, either for germination or seedling development. Smoke can stimulate different stages of the plant life cycle, which can alter the community and invasion processes. So far, most research on the subject focuses on germination, not addressing post-germinative phases, a sensitive stage of plant development. Here, we investigated the effect of smoke on a native (Echinolaena inflexa) and an invasive (Urochloa decumbens) grass species common in the Cerrado. We analysed germinative parameters and seedling mass and length after exposing the seeds to dry smoke for 5, 10, 15 or 20 min. Seedling development was assessed by measuring shoot and root systems after cultivating germinated seeds for 3, 7 or 15 d. Smoke did not affect germination percentages. However, fumigation reduced the mean germination time of both species and the germination onset of E. inflexa. U. decumbens had higher length values in all periods of cultivation, whereas mass values only surpassed that of E. inflexa at 15 d. Smoke exposure reduced the aboveground length of 7-d seedlings of U. decumbens, and mass of 15-d plants of both species. Also, smoke enhanced the root investment of the native and invasive species in different cultivation periods. Therefore, studying post-germinative parameters on seedling development may bring further insights into the smoke effects.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Methods
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
Results
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Conclusions
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
Young people are most vulnerable to suicidal behaviours but least likely to seek help. A more elaborate study of the intrinsic and extrinsic correlates of suicidal ideation and behaviours particularly amid ongoing population-level stressors and the identification of less stigmatising markers in representative youth populations is essential.
Methods
Participants (n = 2540, aged 15–25) were consecutively recruited from an ongoing large-scale household-based epidemiological youth mental health study in Hong Kong between September 2019 and 2021. Lifetime and 12-month prevalence of suicidal ideation, plan, and attempt were assessed, alongside suicide-related rumination, hopelessness and neuroticism, personal and population-level stressors, family functioning, cognitive ability, lifetime non-suicidal self-harm, 12-month major depressive disorder (MDD), and alcohol use.
Results
The 12-month prevalence of suicidal ideation, ideation-only (no plan or attempt), plan, and attempt was 20.0, 15.4, 4.6, and 1.3%, respectively. Importantly, multivariable logistic regression findings revealed that suicide-related rumination was the only factor associated with all four suicidal outcomes (all p < 0.01). Among those with suicidal ideation (two-stage approach), intrinsic factors, including suicide-related rumination, poorer cognitive ability, and 12-month MDE, were specifically associated with suicide plan, while extrinsic factors, including coronavirus disease 2019 (COVID-19) stressors, poorer family functioning, and personal life stressors, as well as non-suicidal self-harm, were specifically associated with suicide attempt.
Conclusions
Suicide-related rumination, population-level COVID-19 stressors, and poorer family functioning may be important less-stigmatising markers for youth suicidal risks. The respective roles played by not only intrinsic but also extrinsic factors in suicide plan and attempt using a two-stage approach should be considered in future preventative intervention work.
OBJECTIVES/GOALS: To summarize baseline characteristics and risk factors for major adverse cardiovascular events (MACEs) and develop a prediction model by testing the association between genetic variants and MACEs in Caribbean Hispanic patients on clopidogrel using machine-learning (ML) techniques. METHODS/STUDY POPULATION: This is a secondary analysis of available clinical and genomic data from an existing database of 600 Caribbean Hispanic cardiovascular (CV) patients on clopidogrel. MACEs is defined as the composite of all-cause death, myocardial infarction, stroke and stent thrombosis over 6 months. Dataset is divided into training (60%) and testing (40%) sets, respectively. Two different supervised ML approaches (i.e. multiclass classification and regression algorithms) are applied to the study dataset using Python v3.5 and WEKA, and tested by receiver operating curve (ROC) analysis. A case-control association analysis between MACEs at 6 months and genotypes is performed by using chi-squared test. RESULTS/ANTICIPATED RESULTS: Average age of participants was 68 years-old, 55% males, with high prevalence of risk factors (i.e., overweight: 28.4 kg/m2; hypertension: 83.8%; hypercholesterolemia: 71.9% and diabetes: 54.8%). MACEs rate is 13.8%, with 33.5% resistant to clopidogrel. Logistic regression, KNN and gradient boosting showed the best performance, as suggested by ROC analysis and AUC CV scores of 0.6-0.7. A significant association between MACE occurrence and ≥3 risk alleles was found (OR=8.17; p=0.041). We anticipate that these genetic variants (CYP2C19*2, rs12777823, PON1-rs662, ABCB1-rs2032582, PEAR1-rs12041331) will uniquely contribute to clopidogrel resistance and MACEs in Caribbean Hispanics. DISCUSSION/SIGNIFICANCE: Our findings help address in part the long-standing problem of excluding minorities from research, which entails a gap of knowledge about clopidogrel pharmacogenomics in Puerto Ricans. This study provides a possible ML model that integrates clinical and pharmacogenomics for MACE risk estimation.