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ABSTRACT IMPACT: Implement and evaluate a fellowship program to foster a new generation of entrepreneurial and collaboratively-minded team scientists, equipped with the knowledge and skills to innovate technology-based solutions for COVID-19 to advance human health OBJECTIVES/GOALS: Mount Sinai Targeted Healthcare Innovation Fellowship (THRIVE) is a 9-month program for participants from diverse professional backgrounds to develop HealthTech innovations related to COVID-19. The program is designed to provide an experiential team science platform for fellows to take an idea from concept to commercially viable innovation. METHODS/STUDY POPULATION: Following a competitive application process, 16 THRIVE fellows comprise four teams working collaboratively in an online forum with input from experts in the field. Success of the program will be evaluated by:
assessing pre- and post- collaborative research orientation among THRIVE fellows using the ROI scale1
using social network analysis (SNA) to investigate the social networks of THRIVE fellows to capture patterns of communication and collaboration related to innovation development
exploring participant experiences of group formation, teamwork and collaboration related to innovation development using one-to-one semi-structured interview
determining team success in innovation development, measured by number of publications, funding awarded, provisional patents and viable products. RESULTS/ANTICIPATED RESULTS: Paired t-tests will determine whether collaborative orientation of THRIVE fellows changes pre- vs. post- program participation, indicating changes in attitude toward multidisciplinary team work. SNA will be used to describe structural patterns of communication that occur at individual and group levels. Network-level indices will provide insight into patterns of communication that exist in innovation development: degree centrality (number of connections per individual), betweenness centrality (number of bridges to others in a network), closeness centrality (closeness to others in a network). We will also test for associations between network characteristics and team success. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding patterns of formal and informal relationships, interactions, and perceptions of the collaborative process among individuals in THRIVE teams will elucidate whether such a program can provide an effective forum for team science and innovation development related to COVID-19.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.
The triarchic model was advanced as an integrative, trait-based framework for investigating psychopathy using different assessment methods and across developmental periods. Recent research has shown that the triarchic traits of boldness, meanness, and disinhibition can be operationalized effectively in youth, but longitudinal research is needed to realize the model's potential to advance developmental understanding of psychopathy. We report on the creation and validation of scale measures of the triarchic traits using questionnaire items available in the University of Southern California Risk Factors for Antisocial Behavior (RFAB) project, a large-scale longitudinal study of the development of antisocial behavior that includes measures from multiple modalities (self-report, informant rating, clinical-diagnostic, task-behavioral, physiological). Using a construct-rating and psychometric refinement approach, we developed triarchic scales that showed acceptable reliability, expected intercorrelations, and good temporal stability. The scales showed theory-consistent relations with external criteria including measures of psychopathy, internalizing/externalizing psychopathology, antisocial behavior, and substance use. Findings demonstrate the viability of measuring triarchic traits in the RFAB sample, extend the known nomological network of these traits into the developmental realm, and provide a foundation for follow-up studies examining the etiology of psychopathic traits and their relations with multimodal measures of cognitive-affective function and proneness to clinical problems.
Hemiparetic walking after stroke is typically slow, asymmetric, and inefficient, significantly impacting activities of daily living. Extensive research shows that functional, intensive, and task-specific gait training is instrumental for effective gait rehabilitation, characteristics that our group aims to encourage with soft robotic exosuits. However, standard clinical assessments may lack the precision and frequency to detect subtle changes in intervention efficacy during both conventional and exosuit-assisted gait training, potentially impeding targeted therapy regimes. In this paper, we use exosuit-integrated inertial sensors to reconstruct three clinically meaningful gait metrics related to circumduction, foot clearance, and stride length. Our method corrects sensor drift using instantaneous information from both sides of the body. This approach makes our method robust to irregular walking conditions poststroke as well as usable in real-time applications, such as real-time movement monitoring, exosuit assistance control, and biofeedback. We validate our algorithm in eight people poststroke in comparison to lab-based optical motion capture. Mean errors were below 0.2 cm (9.9%) for circumduction, −0.6 cm (−3.5%) for foot clearance, and 3.8 cm (3.6%) for stride length. A single-participant case study shows our technique’s promise in daily-living environments by detecting exosuit-induced changes in gait while walking in a busy outdoor plaza.
An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
Observations of teleseismic earthquakes using broadband seismometers on the Ross Ice Shelf (RIS) must contend with environmental and structural processes that do not exist for land-sited seismometers. Important considerations are: (1) a broadband, multi-mode ambient wavefield excited by ocean gravity wave interactions with the ice shelf; (2) body wave reverberations produced by seismic impedance contrasts at the ice/water and water/seafloor interfaces and (3) decoupling of the solid Earth horizontal wavefield by the sub-shelf water column. We analyze seasonal and geographic variations in signal-to-noise ratios for teleseismic P-wave (0.5–2.0 s), S-wave (10–15 s) and surface wave (13–25 s) arrivals relative to the RIS noise field. We use ice and water layer reverberations generated by teleseismic P-waves to accurately estimate the sub-station thicknesses of these layers. We present observations consistent with the theoretically predicted transition of the water column from compressible to incompressible mechanics, relevant for vertically incident solid Earth waves with periods longer than 3 s. Finally, we observe symmetric-mode Lamb waves generated by teleseismic S-waves incident on the grounding zones. Despite their complexity, we conclude that teleseismic coda can be utilized for passive imaging of sub-shelf Earth structure, although longer deployments relative to conventional land-sited seismometers will be necessary to acquire adequate data.
We performed a cross-sectional survey of infection preventionists in 60 US community hospitals between April 22 and May 8, 2020. Several differences in hospital preparedness for SARS-CoV-2 emerged with respect to personal protective equipment conservation strategies, protocols related to testing, universal masking, and restarting elective procedures.
Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.
Introduction: Emergency Department (ED) crowding is an international health system issue that is worsening. Further, ED crowding and “hallway medicine” has been identified as one of the most significant healthcare challenges currently facing Canadians. One contributor is preventable transfers from long-term care facilities (LTCFs) to Emergency Departments (EDs). In Canada, there were 63,752 LTCF patient transfers to the ED in 2014, with 24% (15,202) of them due to potentially preventable conditions. Each preventable transfer exposes patients to transport and hospital-related complications, and costs the healthcare system thousands of dollars. There have been many proposed and studied interventions aimed at alleviating the issue, but few attempts to assess and evaluate different interventions across institutions in a systematic manner. Methods: A scoping review of the literature using three electronic databases was conducted. A scoping review methodology was used due to the range of interventions and the heterogeneity in study design and outcome. Inclusion criteria included: studies on interventions designed to reduce transfers from LTCFs, studies that reported key outcomes such as number of ED transfers, and studies with a control or comparison group. Articles were screened by two independent reviewers (Cohen's k = 0.68), and study quality was assessed using the National Heart, Lung, Blood Institute quality assessment tools. Results: Findings were organized into five intervention types (telemedicine, outreach teams, interdisciplinary teams, integrated approaches, and other), and both a tabular and narrative synthesis was completed. Eleven studies had a good quality assessment rating, 13 studies had a fair rating, and two studies had a poor rating. Twenty out of the 26 studies reported statistically significant reductions in ED transfer rate, ranging from 10-70%. Interdisciplinary healthcare teams staffed within LTCFs were the most effective interventions. Conclusion: There are several promising interventions that have successfully reduced the number of preventable transfers from LTCFs to EDs, in a variety of health system settings. Further analysis of the relative resource requirements of each intervention, and practices that can enable successful implementation are needed to inform healthcare policy and administrative decision making. Widespread implementation of these interventions has the potential to considerably reduce ED crowding.
To evaluate efficacy and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, in obese (BMI =30kg/m2) and non-obese (BMI <30kg/m2) patients with schizophrenia.
Data from a 38-week, double-blind, active-controlled, non-inferiority study (NCT00706654); randomisation (2:2:1) to AOM-400mg, oral aripiprazole (10-30mg/day) (ARI), or aripiprazole once-monthly 50mg (AOM-50mg) assessing the efficacy and safety of AOM in patients requiring chronic antipsychotic treatment were used for this post-hoc analysis. We report the overall relapse rates in the 38-week randomized phase. Comparisons of overall relapse rates were analyzed using the Chi-squared test.
662 patients were randomized to: AOM-400mg (n=265); ARI (n=266); or AOM-50mg (n=131). Of these, the following were obese: AOM- 400mg: n=95; ARI: n=95; AOM-50mg: n=43. In the obese patients, the overall relapse rate was significantly (p=0.0012) lower with AOM-400mg (7.4%) than with AOM-50mg (27.9%). The difference between AOM-400mg and ARI (8.4%) was not significantly different. In the non-obese patients, the overall relapse was significantly (p=0.0153) lower with AOM-400mg (8.8%) than with AOM-50mg (19.3%). The difference between AOM-400mg and ARI (7.6%) was not significantly different. For patients treated with AOM-400mg, the most common TEAEs (>10% in any group) are presented in Table 1.
Injection site pain
Upper respiriatory tract infection
The efficacy and tolerability of aripiprazole once-monthly 400mg were similar in both the obese and non-obese subgroups.
Supported by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S
This study directly compares the effectiveness of aripiprazole once-monthly 400 mg (AOM) and paliperidone palmitate once-monthly (PP) on the validated and symptom-focused Heinrichs-Carpenter Quality-of-Life Scale (QLS) in schizophrenia.
A 28-week, randomized, open-label rater-blinded, head-to-head study (NCT01795547) of AOM and PP in adult patients (18-60 years) needing a change from current oral antipsychotic treatment for any reason. The study comprised oral conversion, initiation of AOM or PP treatment according to labels, and treatment continuation with injections every 4 weeks. The primary endpoint assessed non-inferiority and subsequently superiority on change from baseline to week 28 in QLS total score analyzed using a mixed model for repeated measurements.
Of 295 randomized patients, 100/148 (67.6%) of AOM and 83/147 (56.5%) of PP patients completed 28 weeks of treatment. In treated patients, adverse events (AEs) were the most frequent reason for discontinuation; AOM: 16/144 (11.1%), PP: 27/137 (19.7%). The difference in change from baseline to week 28 on QLS total score was statistically significant (4.67 [95%CI: 0.32;9.02], p=0.036), confirming non-inferiority and establishing superiority of AOM compared to PP. The respective changes were 7.47±1.53 for AOM and 2.80±1.62 for PP. AEs occurring at rates ≥5% in either group in the treatment continuation phase were weight increased (AOM: 12/119 [10.1%]; PP: 17/109 [15.6%]), psychotic disorder (AOM: 3/119 [2.5%]; PP: 6/109 [5.5%]) and insomnia (AOM: 3/119 [2.5%]; PP: 6/109 [5.5%]).
Superior improvements on the clinician-rated QLS and lower rates of all-cause discontinuation suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate.
To evaluate the initial (3 months) all-cause discontinuation and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, stratified by previous treatment.
These two studies (NCT00705783 & NCT00706654) were double-blind, placebo- or active-controlled assessing the efficacy and safety of AOM-400mg. Detailed study designs have been reported previously (1, 2). This analysis was conducted on the pooled population in the first 3 months after initiating AOM-400mg treatment, on patients who received at least one dose of AOM-400mg. Outcome measures are reported for groups stratified by prior treatment.
During the first 3 months of treatment, discontinuation due to all-causes (except for those who discontinued due to the sponsor stopping the NCT00705783 study early after pre-specified efficacy parameters were met) as well as due to adverse events are presented in Table 1. The rates of insomnia and akathisia are shown in Table 1
Aripiprazole once-monthly 400mg appeared equally safe and effective (as measured by all cause discontinuation) in the first 3 months after initiation, regardless of treatment prior to entering trials.
Antipsychotic other than oral aripiprazole (converted) n=581
Single nucleotide polymorphisms (SNPs) contribute small increases in risk for late-onset Alzheimer's disease (LOAD). LOAD SNPs cluster around genes with similar biological functions (pathways). Polygenic risk scores (PRS) aggregate the effect of SNPs genome-wide. However, this approach has not been widely used for SNPs within specific pathways.
We investigated whether pathway-specific PRS were significant predictors of LOAD case/control status.
We mapped SNPs to genes within 8 pathways implicated in LOAD. For our polygenic analysis, the discovery sample comprised 13,831 LOAD cases and 29,877 controls. LOAD risk alleles for SNPs in our 8 pathways were identified at a P-value threshold of 0.5. Pathway-specific PRS were calculated in a target sample of 3332 cases and 9832 controls. The genetic data were pruned with R2 > 0.2 while retaining the SNPs most significantly associated with AD. We tested whether pathway-specific PRS were associated with LOAD using logistic regression, adjusting for age, sex, country, and principal components. We report the proportion of variance in liability explained by each pathway.
The most strongly associated pathways were the immune response (NSNPs = 9304, = 5.63 × 10−19, R2 = 0.04) and hemostasis (NSNPs = 7832, P = 5.47 × 10−7, R2 = 0.015). Regulation of endocytosis, hematopoietic cell lineage, cholesterol transport, clathrin and protein folding were also significantly associated but accounted for less than 1% of the variance. With APOE excluded, all pathways remained significant except proteasome-ubiquitin activity and protein folding.
Genetic risk for LOAD can be split into contributions from different biological pathways. These offer a means to explore disease mechanisms and to stratify patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological interventions. Fluoxetine, paroxetine, sertraline and venlafaxine are the best-evidenced drugs, with lower-level evidence for other medications. It is important that prescribing for PTSD is evidence-based.
The Ross Ice Shelf (RIS) is host to a broadband, multimode seismic wavefield that is excited in response to atmospheric, oceanic and solid Earth source processes. A 34-station broadband seismographic network installed on the RIS from late 2014 through early 2017 produced continuous vibrational observations of Earth's largest ice shelf at both floating and grounded locations. We characterize temporal and spatial variations in broadband ambient wavefield power, with a focus on period bands associated with primary (10–20 s) and secondary (5–10 s) microseism signals, and an oceanic source process near the ice front (0.4–4.0 s). Horizontal component signals on floating stations overwhelmingly reflect oceanic excitations year-round due to near-complete isolation from solid Earth shear waves. The spectrum at all periods is shown to be strongly modulated by the concentration of sea ice near the ice shelf front. Contiguous and extensive sea ice damps ocean wave coupling sufficiently so that wintertime background levels can approach or surpass those of land-sited stations in Antarctica.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
In part, our understanding of contemporary sectarianism in the Middle East is based on a misunderstanding of the origins and development of Muslim sectarian identities. We tend to view Sunni Islam as the original or orthodox Islam while we portray all other Islams, such as Shiʿism, as heterodox deviations from the original. This book aims to dispel this misconception. While Sunni Islam eventually became politically and numerically dominant, Sunni and Shiʿi identities took centuries to develop as independent communities with fully articulated theologies and practices. Rather than seeing Sunnis and Shiʿis as having split and never come back together, it is more accurate to view the early Muslim community as espousing a diversity of formulations of Islam that eventually, over centuries, narrowed into the sectarian identities that we can recognize today.
Further, due to modern sectarian conflicts, we tend to assume that enmity and violence have been a constant feature of the Sunni–Shiʿi relationship. On the contrary, this book will reveal how the idea of Muslim sectarian hostility developed relatively late in Islamic history by analysing two tenth-century Shiʿi dynasties, the Fatimids (909–1171) of North Africa and the Buyids (945–1055) of Iraq and Iran, investigating how they articulated their power, and how local Sunnis reacted to them.
Islamic sectarianism has received a great deal of attention recently due to contemporary events in the Middle East: the collapse of Iraq following the U.S. invasion in 2003, the ongoing Syrian civil war, protests led by Shiʿi groups in Yemen and the Gulf States, the tension between Sunni Saudi Arabia and Shiʿi Iran, and the rise of extremist Sunni organizations like Daesh/ISIS and al-Qaeda that violently target Shiʿi Muslims. These current conflicts in the Middle East, with their empha-sis on sectarian identities, have led historians and political scientists to coin the term “sectarianization” as the process by which political actors use aspects of sectarian identity to exacerbate existing conflicts for their own benefit.
It can be easy to blame sectarianism for contemporary and historical conflicts in the Middle East, especially when the causes seem hard to explain.