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Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.
OBJECTIVES/GOALS: Neuroblastoma (NB) is the most common extra-cranial solid tumor with outcomes varying from spontaneous regression to metastatic with high mortality rates. The tumor immune microenvironment (TIME) may play a significant role in this disease. In this study we analyze the TIME comparing high-risk (HR) and low-risk (LR) NBs using multiplex platforms. METHODS/STUDY POPULATION: Two tissue microarrays (TMAs) with 2mm cores were created from 41 patients treated at Columbia University Irving Medical Center. Five micron TMA slides were stained for Digital Spatial Profiling (DSP, nanoString) and multiplex immunofluorescence (mIF). For DSP, a 24-patient subset including 11 HR, 8 LR and 4 intermediate risk patients was analyzed for 34 proteins. Protein expression among risk groups was compared using Mann-Whitney t-test. For mIF, TMA FFPE slides were stained for DAPI, CD3, CD8, CD68, HLA-DR, PDL1 and Chromogranin A. Whole TMA cores were captured as 9 -20X multispectral images (MSIs) stitched into a 3x3 MSI using Vectra (Akoya). MSIs were processed with inForm and qualitative analysis performed comparing HR and LR tumors. RESULTS/ANTICIPATED RESULTS: With DSP, we find significantly more HLA-DR in HR compared to LR tumors (p = 0.016). When controlling for immune cells with CD45 we find HLA-DR/CD45 to be higher in HR than LR tumors (p = 0.026). We found increased PD1 and PDL1 expression in all groups without significant difference between LR and HR (p = 0.778 and p = 0.310, respectively). Preliminary analysis of mIF on 9 patients (4 HR and 5 LR) finds HR tumors appear to have more immune cells than LR tumors, specifically more CD3+CD8- T cells while total CD8+ cells may be similar. There may be less macrophages in the HR compared to LR tumors. Completion of image processing and quantitative analysis of mIF data is underway. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased expression of immune markers in NB TIME correlates with higher risk, which is unlike many other tumors. We compared TIME in HR and LR NB using multiplex platforms, DSP and mIF. We find that HLA-DR is more expressed in HR NB while PD1 and PDL1 expression is consistently high and not different between risk groups. Further analysis is underway. CONFLICT OF INTEREST DESCRIPTION: Robyn D. Gartrell-Corrado received grant support from nanoString for Digital Spatial Profiling and received honoraria and travel support from Northwest Biotherapeutics and PerkinElmer, respectively.
Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.
Emerging research highlights the importance of the timing of the onset of a depressive episode. This study examines the risk factors and psychiatric features of participants who experienced their first major depressive episode as children, teenagers or adults. This study is unique in that it emphasises the importance of examining onset of an episode during critical developmental periods.
Participants were 372 depressed outpatients who were either treated with psychotherapy (IPT or CBT) or medication as part of two separate randomised clinical trials. Participants completed a number of assessment measures including clinician ratings of DSM diagnoses. Personality was also assessed using Cloninger's (e.g., 1994) Temperament and Character Inventory.
Participants with childhood onset and teenage-onset depression had a higher number of co-morbid diagnoses and more DSM III/IV personality disorder diagnoses than those with adult-onset depression. Specifically, more participants with childhood or teenage onset depression had diagnoses of avoidant and borderline personality disorder. Women who had childhood onset depression were over three times more likely to have attempted suicide compared to other participants. Participants with childhood onset depression were also more likely to report being threatened with abuse, have experienced psychological abuse and reported more abuse incidents. Age of onset was also associated with a number of differences in temperament and character.
This research emphasises the significance of understanding the age of onset of a depressive episode. Depressive episodes that begin in childhood/adolescence are associated with higher co-morbidity and greater personality dysfunction.
Examine impact of audit and feedback on antipsychotic prescribing in schizophrenia over 4.5-years.
Clinical files in three outpatient psychiatric services in Auckland, New Zealand were reviewed at two time-points (March-2000;October-2004). After the first audit, feedback was provided to all three services. Baseline prescribing variations between services were found for antipsychotic combinations and atypical prescribing, in particular clozapine. In two services audit and feedback continued with two interim reviews (October-2001;March-2003). Specific feedback and interventions targeting clozapine use were introduced in both services. No further audit or feedback occurred in the third service until the final audit. Data were collected (patient characteristics, diagnosis, antipsychotic treatment) and analysed at each audit.
Three prescribing variables (antipsychotic monotherapy, atypical and clozapine use) were consistent with practice recommendations at the final audit (85.7%, 82.7% and 34.5% respectively) and had changed in the desired direction for all three services over 4.5-years. At baseline there were differences between the three services. One service had baseline prescribing variables closest to recommendations, was actively involved in audit, and improved further. The second service, also actively involved in audit had baseline prescribing variables further from recommendations but improved the most. The service not involved in continuing audit and feedback made smaller changes, and atypical and clozapine use at endpoint were significantly lower despite at baseline being comparable to the service which improved the most.
We found high intensity audit and feedback was an effective intervention in closing the gap between recommended and clinical practice for antipsychotic prescribing.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Masses have been computed for the white dwarfs (WDs) in eclipsing, mass exchange (symbiotic), WD–red giant (RG) binaries by using single-lined spectroscopic orbits, orbital inclinations, and the RG masses. Inclinations have been measured for 13 eclipsing symbiotic binaries. Using Gaia data the mass of the RG can be found from evolutionary tracks. Since the WD evolved from the more massive star in the binary, the WD should be more massive than predicted from the mass of the current RG. Typically the WD has a lower mass than expected implying a previous mass exchange stage for these systems.
Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.
Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.
Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.
These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.
Over 80% of CTSA programs have a community advisory board (CAB). Little is known about how research discussed with CABs aligns with community priorities (bidirectionality). This program evaluation assessed researcher presentations from 2014 to 2018 to the CABs linked to our CTSA at all three sites (Minnesota, Arizona, and Florida) for relevance to local community needs identified in 2013 and/or 2016. From content analysis, of 65 presentations total, 41 (63%) addressed ≥1 local health needs (47% Minnesota, 60% Florida, and 80% Arizona). Cross-cutting topics were cancer/cancer prevention (physical activity/obesity/nutrition) and mental health. Results could help to prioritize health outcomes of community-engaged research efforts.
OBJECTIVES/SPECIFIC AIMS: Over 80% of CTSA programs have a community advisory board (CAB), an effective strategy to increase community engagement (CE) in research. Little is known about how the research discussed with CABs aligns with community priorities (i.e., bi-directionality). This program evaluation assessed the health topics presented by researchers to the CABs linked to our CE Program at all three Mayo Clinic sites (MN, AZ, and FL) for relevance to local community needs. METHODS/STUDY POPULATION: Two coders classified Mayo researcher presentations to our CABs from 2014-2018 for relevance to needs identified in the local 2013 and/or 2016 County Health Needs Assessments and specific topic(s); with high levels of agreement (Kappa=0.90). RESULTS/ANTICIPATED RESULTS: Overall, of the 65 presentations 41 (63%) addressed one or more local health needs (47% MN, 60% FL, 80% AZ). Cross-cutting health topics addressed at 2 sites were physical activity/obesity/nutrition and mental health. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings were shared with our CABs to obtain input on future directions. The FL and AZ CABs are systematic in seeking out or initiating research projects that address local health needs, an approach the MN site is interested in adopting. Ultimately, it is important to demonstrate improved health outcomes with CTSA-based CE research strategies. Understanding community health needs and depth of researchers in those areas may help to focus priorities for demonstrating such outcomes.
Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed.
To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses.
Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales.
Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia.
The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia.
Borderline personality disorder (BPD) is characterised by recurring crises, hospitalisations, self-harm, suicide attempts, addictions, episodes of depression, anxiety and aggression and lost productivity. The objective of this study is to determine the use of direct health care resources by persons with BPD in Ireland and the corresponding costs.
This prevalence-based micro-costing study was undertaken on a sample of 196 individuals with BPD attending publicly funded mental health services in Ireland. All health care costs were assessed using a resource utilisation questionnaire completed by mental health practitioners. A probabilistic sensitivity analysis, using a Monte Carlo simulation, was performed to examine uncertainty.
Total direct healthcare cost per individual was €10 844 annually (ranging from 5228 to 20 609). Based on a prevalence of 1% and an adult population (18–65 years) of 2.87 million, we derived that there were 28 725 individuals with BPD in Ireland. Total yearly cost of illness was calculated to be up to €311.5 million.
There is a dearth of data on health care resource use and costs of community mental health services in Ireland. The absence of this data is a considerable constraint to research and decision-making in the area of community mental health services. This paper contributes to the limited literature on resource use and costs in community mental health services in Ireland. The absence of productivity loss data (e.g. absenteeism and presenteeism), non-health care costs (e.g. addiction treatment), and indirect costs (e.g. informal care) from study participants is a limitation of this study.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
Cognitive behaviour therapy (CBT) and interpersonal psychotherapy (IPT) are the most studied psychotherapies for treatment of depression, but they are rarely directly compared particularly over the longer term. This study compares the outcomes of patients treated with CBT and IPT over 10 months and tests whether there are differential or general predictors of outcome.
A single centre randomised controlled trial (RCT) of depressed outpatients treated with weekly CBT or IPT sessions for 16 weeks and then 24 weeks of maintenance CBT or IPT. The principle outcome was depression severity measured using the MADRS. Pre-specified predictors of response were in four domains: demographic depression, characteristics, comorbidity and personality. Data were analysed over 16 weeks and 40 weeks using general linear mixed effects regression models.
CBT was significantly more effective than IPT in reducing depressive symptoms over the 10 month study largely because it appeared to work more quickly. There were no differential predictors of response to CBT v. IPT at 16 weeks or 40 weeks. Personality variables were most strongly associated with overall outcome at both 16 weeks and 40 weeks. The number of personality disorder symptoms and lower self-directness and reward dependence scores were associated with poorer outcome for both CBT and IPT at 40 weeks.
CBT and IPT are effective treatments for major depression over the longer term. CBT may work more quickly. Personality variables are the most relevant predictors of outcome.
Progress in ultrafast terahertz (THz) communications has been limited due to the lack of picosecond switchable modulators with sufficient modulation depth. Gallium arsenide nanowires are ideal candidates for THz modulators as they absorb THz radiation, only when photoexcited – giving the potential for picosecend speed switching and high modulation depth. By embedding the nanowires in a polymer matrix and laminating together several nanowire–polymer films, we increase the areal density of nanowires, resulting in greater modulation of THz radiation. In this paper, we compare PDMS and Parylene C polymers for nanowire encapsulation and show that a high modulation depth is possible using Parylene C due to its thinness and its ability to be laminated. We characterize the modulator behavior and switching speed using optical pump–THz probe spectroscopy, and demonstrate a parylene–nanowire THz modulator with 13.5% modulation depth and 1ps switching speed.
Introduction: Trauma is the leading cause of death among people under 40. With more than 7 million Canadians living over one hour’s travel from a level 1 or 2 trauma center, access to quality trauma care in Canada is a major concern. We recently reported that more than 40% of rural EDs across Canada were more than 300 km from levels 1 and 2 trauma centers. Direct transportation to trauma centers is therefore unusual and most trauma cases are initially managed in rural EDs. Assistance from trauma centers via telemedicine could thus be valuable in optimizing initial stabilization and inter-facility transfers. Objective: Is telemedicine a potentially effective intervention for improving rural trauma care? Methods: We conducted a literature review to examine the potential impact (number of transfers, transfer times, length of hospital stays and mortality) of telemedicine on rural trauma care. Two reviewers independently searched PubMed, Embase and Cochrane databases with key words / concept combinations: telemedicine, trauma and rural. Articles included in the final review had to address the question with specific methodologies. After duplicate removal, 312 articles were found relevant. After independent review of titles and abstracts, only 25 articles pertained to the specific question. Only three studies met inclusion criteria. Results: These studies reported 187 successful teleconsultations in the context of rural trauma care, 29 of which involved significant interventions (8 interventions potentially lifesaving). Some unnecessary inter-facility transfers were avoided. However, transfer times to trauma centers and length of hospital stays appeared slightly longer with telemedicine. Conclusion: The literature on the efficacy of telemedicine in trauma care is scarce, with only three studies addressing the question. Conclusions generally favor telemedicine, but additional research must should determine its impact and better understand the barriers/facilitators to the implementation of telemedicine for rural trauma care.
Imbalances in dietary fat intakes are linked to several chronic diseases. This study describes dietary intakes and food sources of fat and fatty acids in 1051 Irish adults (aged 18–90 years), using data from the 2011 national food consumption survey, the National Adult Nutrition Survey. It also compares current intakes for 18–64-year-olds with those reported in the last such survey in 2001, the North/South Ireland Food Consumption Survey. Dietary fat intakes were estimated using data from 4-d semi-weighed (2011) and 7-d estimated (2001) food diaries. In 2011, intakes for 18–64-year-olds were as follows: total fat, 34·1 (sd 6·1) % total energy (%TE); SFA, 13·3 (sd 3·3) %TE; MUFA, 12·5 (sd 2·6) %TE; PUFA, 6·1 (sd 2·2) %TE; and trans-fat, 0·511 (sd 0·282) %TE. Apart from MUFA, intakes decreased (P<0·001) compared with 2001. There was no statistically significant difference in intakes of EPA and DHA by 18–64-year-olds in 2011 (269·0 (sd 515·0) mg/d) and 2001 (279·1 (sd 497·5) mg/d). In 2011, adults aged >65 years had the highest intakes of SFA; however, intakes were typically higher than UK-recommended values for all groups. In contrast, intakes of long-chain n-3 fatty acids were lowest in younger age groups. Intakes of trans-fat were well within UK-recommended levels. Although there have been some improvements in the profile of intakes since 2001, imbalances persist in the quantity and quality of dietary fat consumed by Irish adults, most notably for total and SFA and for younger age groups for long-chain n-3 fatty acids.