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This study describes the performance of the Multilingual Naming Test (MINT) by Chinese American older adults who are monolingual Chinese speakers. An attempt was also made to identify items that could introduce bias and warrant attention in future investigation.
The MINT was administered to 67 monolingual Chinese older adults as part of the standard dementia evaluation at the Alzheimer’s Disease Research Center (ADRC) at the Icahn School of Medicine at Mount Sinai (ISMMS), New York, USA. A diagnosis of normal cognition (n = 38), mild cognitive impairment (n = 12), and dementia (n = 17) was assigned to all participants at clinical consensus conferences using criterion sheets developed at the ADRC at ISMMS.
MINT scores were negatively correlated with age and positively correlated with education, showing sensitivity to demographic factors. One item, butterfly, showed no variations in responses across diagnostic groups. Inclusion of responses from different regions of China changed the answers from “incorrect” to “correct” on 20 items. The last five items, porthole, anvil, mortar, pestle, and axle, yielded a high nonresponse rate, with more than 70% of participants responding with “I don’t know.” Four items, funnel, witch, seesaw, and wig, were not ordered with respect to item difficulty in the Chinese language. Two items, gauge and witch, were identified as culturally biased for the monolingual group.
Our study highlights the cultural and linguistic differences that might influence the test performance. Future studies are needed to revise the MINT using more universally recognized items of similar word frequency across different cultural and linguistic groups.
Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.
Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.
Patients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.
In this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.
Lumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.
This paper characterizes novel “star” defects in GaN films grown with metal–organic vapor phase deposition (MOVPE) on GaN substrates with electron channeling contrast imaging (ECCI) and high-resolution electron backscatter diffraction (HREBSD). These defects are hundreds of microns in size and tend to aggregate threading dislocations at their centers. They are the intersection of six nearly ideal low-angle tilt boundaries composed of $\langle a\rangle$-type pyramidal edge dislocations, each on a unique slip system.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.
Calcareous loess in North Canterbury, eastern South Island, New Zealand (NZ), preserves subfossil bird bone, terrestrial gastropods, and eggshell, whose abundances and radiocarbon ages allowed us to reconstruct aspects of palaeoenvironment at high resolution through 25 to 21 cal ka BP. This interval includes millennial-scale climatic variability during the extended last glacial maximum (30–18 ka) of Australasia. Our loess palaeoclimatic record shows good correspondence with stadial and interstadial climate events of the NZ Climate Event Stratigraphy, which were defined from a pollen record on the western side of South Island. An interstade from 25.4 to 24 cal ka BP was warm but also relatively humid on eastern South Island, and loess grain size may indicate reduced vigour of the Southern Hemisphere westerly winds. The subsequent stade (24–22.6 cal ka BP) was drier, colder, and probably windier. The next interstade remained relatively dry on eastern South Island, and westerly winds remained vigorous. The 25.4–24 ka interstade is synchronous with Heinrich stade 2, which may have driven a southward migration of the subtropical front, leading to warming and wetting of northern and central South Island and retreat of Southern Alps glaciers at ca. 26.5 ka.
Social and economic changes associated with new roads can bring about rapid nutritional transitions. To study this process, we: (1) describe trends in adult overweight and obesity (OW/OB) among rural Afro-Ecuadorians over time and across a gradient of community remoteness from the nearest commercial centre; (2) examine the relationship between male and female adult OW/OB and factors associated with market integration such as changing livelihoods and (3) examine the co-occurrence of adult OW/OB and under-five stunting and anaemia.
Adult anthropometry was collected through serial case–control studies repeated over a decade across twenty-eight communities. At the same time, anthropometry and Hb were measured for all children under 5 years of age in every community.
Northern coastal Ecuador.
Adults (n 1665) and children under 5 years of age (n 2618).
From 2003 and 2013, OW/OB increased from 25·1 % to 44·8 % among men and 59·9 % to 70·2 % among women. The inverse relationship between remoteness and OW/OB in men was attenuated when adjusting for urban employment, suggesting that livelihoods mediated the remoteness–OW/OB relationship. No such relationship was observed among women. Communities with a higher prevalence of male OW/OB also had a greater prevalence of stunting, but not anaemia, in children under 5 years of age.
The association between male OW/OB and child stunting at the community level, but not the household level, suggests that changing food environments, rather than household- or individual-level factors, drove these trends. A closer examination of changing socio-economic structures and food environments in communities undergoing rapid development could help mitigate future public health burdens.
Background: Approximately two-thirds of children aged <5 years receive out-of-home child care. Childcare attendees have an increased risk of infections compared to children not in childcare settings, possibly due to their close contact in a shared environment. As multidrug-resistant organisms (MDROs) increasingly move from healthcare-associated to community settings, childcare can provide a venue for further transmission of these pathogens. Our objective was to evaluate the bioburden of pathogens present on fomites in childcare centers and how surface contamination changes over time. Methods: The study was conducted in the single-room play area of an Ypsilanti, Michigan, childcare center caring for children aged 3–5 years. Polyester swabs were used to collect surface samples from 16 locations in the room, including (1) laminate, wood and plastic tabletops and furniture; (2) a stainless steel sink and adjacent plastic trash bin; and (3) wood, metal and plastic toys. A water sample was also collected at a 17th site. Samples were collected twice weekly for 5 of 6 weeks, followed by 1 additional collection (September–October 2019). Tryptic soy agar was used for standard plate counts and selective media were used to identify methicillin-resistant Staphylococcus aureus (MRSA), Vvancomycin-resistant Enterococcus (VRE), and extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae. Single-plex RT-PCR was used to detect norovirus and adenovirus. Results: Among 175 samples collected on 11 days, MRSA and ESBL-producing Enterobacteriaceae were detected from 10.3% (18 of 175) and 8.0% (14 of 175), respectively, of environmental specimens. No specimens were positive for VRE or norovirus. Adenovirus was detected in 20 of 175 specimens (11.4%). Median bioburden by site ranged from 85 CFU/mL to 2,510 CFU/mL. The highest median bioburden was observed at the sink (2,510 CFU/mL), followed by the plastic building block table (1,620 CFU/mL), the small wood blocks (1,565 CFU/mL) and water from a water play area and an adjacent tabletop (1,260 and 1,100 CFU/mL respectively). The highest single day bioburden was 273,000 CFU/mL at the sink. Conclusion: The presence of MDROs on childcare center fomites raised concern for exposure to these pathogens among vulnerable populations. More study is needed to determine the degree to which these contaminated fomites drive transmission between children. We found the highest bioburdens on sites where children played or washed with water, identifying potential targets for more frequent cleaning.
Disclosures: Emily T. Martin reports a consulting from Pfizer.
Healthcare workers (HCWs) have a theoretically increased risk of contracting severe acute respiratory coronavirus virus 2 (SARS-CoV-2) given their occupational exposure. We tested 2,167 HCWs in a London Acute Integrated Care Organisation for antibodies to SARS-CoV-2 in May and June 2020 to evaluate seroprevalence. We found a seropositivity rate of 31.6% among HCWs.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
OBJECTIVES/GOALS: Acetaminophen (Tylenol, APAP) toxicity has been well documented and well explored over the last 50 years. However, there has been no investigation into identification of specific metabolites that can predict which patients will have adverse reactions to therapeutic doses of APAP. METHODS/STUDY POPULATION: 205 subjects recruited from the Denver, CO community received the highest recommended daily dosing of APAP, 4 grams, for 16 days. Subjects were grouped by 1) alanine aminotransferase (ALT) at any monitored time point above 60units/L (n = 20) vs 2) no increase in ALT at any time point (n = 185). Blood was collected at days 0, 4, 7, 16, and 31. Samples were run on ultra-high performance liquid chromatography mass spectrometry with 27 heavy-labeled standards for metabolites documented to be associated with APAP metabolism. Data will be analyzed to look for significant changes in metabolite and demographic variable expressions using t-tests, chi square and logistic regression, as appropriate. RESULTS/ANTICIPATED RESULTS: It is expected that there will be greater elevations of conjugated non-toxic APAP metabolites (APAP-glucuronide, APAP-sulfate) in subjects whose ALT did not elevate because of successful hepatoprotection. Conjugated APAP metabolites are expected to only be present in samples taken after APAP therapy initiation confirming exposure as compared to being predictive of toxic response. Increases in lactate and cysteine in pre-exposure samples would allow for prediction of APAP toxicity as they are expected to have increased expression in subjects whose ALT became elevated which is indicative of increased hepatic damage due to oxidative damage. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of metabolites and/or demographic factors associated with toxic response to APAP prior to administration could advise APAP recommendations. Quantification of post-APAP administration metabolites would identify extent of successful hepatoprotective mechanisms.
OBJECTIVES/GOALS: A particularly debilitating consequence of stroke is alexia, an acquired impairment in reading. Cognitive models aim to characterize how information is processed based on behavioral data. If we can concurrently characterize how neural networks process that information, we can enhance the models to reflect the neuronal interactions that drive them. METHODS/STUDY POPULATION: There will be 10 unimpaired adult readers. Two functional localizer tasks, deigned to consistently activate robust language areas, identify the regions of interest that process the cognitive reading functions (orthography, phonology, semantics). Another task, designed for this experiment, analyses the reading-related functional-connectivity between these areas by presenting words classified along the attributes of frequency, concreteness, and regularity, which utilize specific cognitive routes, and a visual control. Connectivity is analyzed during word reading overall vs. a control condition to determine overall reading-related connectivity, and while reading words that have high vs. low attribute values, to determine if cognitive processing routes bias the neural reading network connectivity. RESULTS/ANTICIPATED RESULTS: The localizer analysis is expected to result in the activation of canonical reading areas. The degree of functional connectivity observed between these regions is expected to depend on the degree to which each cognitive route is utilized to read a given word. After orthographic, phonologic, and semantic areas have been identified, the connectivity analysis should show that there is high correlation between all three types of areas during reading compared to the control condition. Then the frequency, regularity, and concreteness of the words being read should alter the reliance on the pathways between these area types. This would support the hypothesized pattern of connectivity as predicted by the cognitive reading routes. Otherwise, it will show how the neural reading network differs from the cognitive model. DISCUSSION/SIGNIFICANCE OF IMPACT: The results will determine the relationship between the cognitive reading model and the neural reading network. Cognitive models show what processes occur in the brain, but neural networks show how these processes occur. By relating these components, we obtain a more complete view of reading in the brain, which can inform future alexia treatments.
OBJECTIVES/GOALS: Utilizing clinical electronic health record (eHR) data pulled en masse from data warehouses provides unique challenges when applying it to retrospective studies. Use of this data in conjunction with metabolomic and genomic results to predict response to lisinopril or ondansetron has been completed. METHODS/STUDY POPULATION: Study population consists of >2000 subjects recruited from the Emergency Medicine Specimen Bank at University of Colorado Denver (UCD). All patients presenting to the emergency department are approached to participate which significantly increases demographic diversity of our study populations. Clinical data is pulled from Health Data Compass (data warehouse at UCD that collects all electronic health record (EHR) data to be able to deliver de-identified). Effectiveness of lisinopril and ondansetron were investigated using metabolomic data collected via ultra-high performance liquid chromatography mass spectrometry and genomic data from Illumina chip technology to find relevant correlations. RESULTS/ANTICIPATED RESULTS: Obtaining retrospective clinical data from data warehouses comes with significant challenges to be addressed. Verifying all clinical variables from patient EHRs is a crucial step that requires extensive quality control steps. As well, ensuring data validity, appropriateness of data points pulled as relate to the study criteria and identifying alternate EHR data points is needed. Chart review is a critical step necessary to surmount these challenges. Additionally, use of retrospective EHR data often necessitates the development of novel definitions of clinical effectiveness that can be abstracted from the EHR– such as how to determine decrease in nausea without a visual analogue scale. DISCUSSION/SIGNIFICANCE OF IMPACT: Utilizing data warehouses to deliver EHR data provides a valuable tool for completing retrospective precision medicine projects. The validation of definitions for clinical outcomes identifiable retrospectively are necessary and provide novel guidance for future studies.
This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program – Neuroreader™.
Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models.
Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses.
This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.