Brown University

• Providence, Rhode Island, United States
Recent publications
Background In response to the coronavirus disease (COVID-19) pandemic, Project HOPE®, an international humanitarian organization, partnered with Brown University to develop and deploy a virtual training-of-trainers (TOT) program to provide practical knowledge to healthcare stakeholders. This study is designed to evaluate this TOT program. Objective The goal of this study is to assess the effectiveness of this educational intervention in enhancing knowledge on COVID-19 concepts and to present relative change in score of each competency domains of the training. Methods The training was created by interdisciplinary faculty from Brown University and delivered virtually. Training included eight COVID-19 specific modules on infection prevention and control, screening and triage, diagnosis and management, stabilization and resuscitation, surge capacity, surveillance, and risk communication and community education. The assessment of knowledge attainment in each of the course competency domain was conducted using 10 question pre-and post-test evaluations. Paired t-test were used to compare interval knowledge scores in the overall cohort and stratified by WHO regions. TOT dissemination data was collected from in-country partners by Project Hope. Results Over the period of 7 months, 4,291 personnel completed the TOT training in 55 countries, including all WHO regions. Pre-test and post-test were completed by 1,198 and 706 primary training participants, respectively. The mean scores on the pre-test and post-test were 68.45% and 81.4%, respectively. The mean change in score was 11.72%, with P value <0.0005. All WHO regions had a statistically significant improvement in their score in post-test. The training was disseminated to 97,809 health workers through local secondary training. Conclusion Innovative educational tools resulted in improvement in knowledge related to the COVID-19 pandemic, significantly increasing the average score on knowledge assessment testing. Academic – humanitarian partnerships can serve to implement and disseminate effective education rapidly across the globe.
Studies identifying bacterial members that dictate host phenotype have focused mainly on the dominant members, and the role of low abundance microbes in determining host phenotypes and pathogenesis of diseases remains unexplored. In this study, we compared the gut bacterial community of mice with wide-ranging microbial exposure to determine if low abundance bacteria vary based on microbial exposure or remain consistent. We noted that similar to the high abundance bacterial community, a core community of low abundance bacteria made up a significant portion of the gut microbiome irrespective of microbial exposure. To determine the role of low abundance bacteria in regulating community composition and host gene expression, we devised a microbiome dilution strategy to "delete" out low abundance bacteria and engrafted the diluted microbiomes into germ-free mice. Our approach successfully excluded low abundance bacteria from small and large intestinal bacterial communities and induced global changes in microbial community composition in the large intestine. Gene expression analysis of intestinal tissue revealed that loss of low abundance bacteria resulted in a drastic reduction in expression of multiple genes involved MHCII antigen presentation pathway and T-cell cytokine production in the small intestine. The effect of low abundance bacteria on MHCII expression was found to be specific to the intestinal epithelium at an early timepoint post-colonization and correlated with bacteria belonging to the family Erysipelotrichaceae. We conclude that low abundance bacteria have a significantly higher immuno-stimulatory effect compared to dominant bacteria and are thus potent drivers of early immune education in the gut.
While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital’s image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.
Background Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC. Methods and results We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients ( N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97–1.00; CD8T: HR = 0.97, 95% CI = 0.95–1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00–1.07; mdNLR: HR = 1.12, 95% CI = 1.04–1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death ( P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites. Conclusions Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.
Background Myeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype. Results Using the Illumina EPIC array to measure DNAm of gMDSCs and neutrophils from diverse neonatal and adult blood sources, we found 189 differentially methylated CpGs between gMDSCs and neutrophils with a core of ten differentially methylated CpGs that were consistent across both sources of cells. Genes associated with these loci that are involved in immune responses include VCL, FATS, YAP1, KREMEN2, UBTF, MCC-1, and EFCC1. In two cancer patient groups that reflected those used to develop the methylation markers (head and neck squamous cell carcinoma (HNSCC) and glioma), all of the CpG loci were differentially methylated, reaching statistical significance in glioma cases and controls, while one was significantly different in the smaller HNSCC group. Conclusions Our findings indicate that gMDSCs have a core of distinct DNAm alterations, informing future research on gMDSC differentiation and function.
We consider the derivation of the defocusing cubic nonlinear Schrödinger equation (NLS) on R3\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathbb {R}}^{3}$$\end{document} from quantum N-body dynamics. We reformat the hierarchy approach with Klainerman-Machedon theory and prove a bi-scattering theorem for the NLS to obtain convergence rate estimates under H1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H^{1}$$\end{document} regularity. The H1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H^{1}$$\end{document} convergence rate estimate we obtain is almost optimal for H1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$H^{1}$$\end{document} datum, and immediately improves if we have any extra regularity on the limiting initial one-particle state.
The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
Background Drug overdose and firearm injury are two of the United States (US) most unrelenting public health crises, both of which have been compounded by the COVID-19 pandemic. Programs and policies typically focus on each epidemic, alone, which may produce less efficient interventions if overlap does exist. The objective is to examine whether drug overdose correlates with and is associated with firearm injury at the census tract level while controlling for neighborhood characteristics. Methods An ecological study of census tracts in Indianapolis, Indiana from 2018 to 2020. Population rates per 100,000 and census tracts with the highest overlap of overdose and firearm injury were identified based on spatial clusters. Bivariate association between census tract characteristic and drug overdose and firearm violence rate within spatial clusters. Zero-inflated negative binominal regression was used to estimate if the drug overdose activity is associated with higher future firearm injury. Results In high overdose—high firearm injury census tracts, rates of firearm injury and drug overdose are two times higher compared to city wide rates. Indicators of structural disadvantage and structural racism are higher in high overdose—high firearm injury census tracts compared to city-wide averages. Drug overdoses are associated with higher rates of firearm injury in the following year (IRR: 1.004, 95% CI 1.001, 1.007, p < 0.05), adjusting for census tract characteristics and spatial dependence. Conclusions Drug overdose and firearm injury co-spatially concentrate within census tracts. Moreover, drug overdoses are associated with future firearm injury. Interventions to reduce firearm injuries and drug overdoses should be a co-response in high drug overdose—high firearm injury communities.
Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15–12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.
When navigating uncertain worlds, humans must balance exploring new options versus exploiting known rewards. Longer horizons and spatially structured option values encourage humans to explore, but the impact of real-world cognitive constraints such as environment size and memory demands on explore-exploit decisions is unclear. In the present study, humans chose between options varying in uncertainty during a multi-armed bandit task with varying environment size and memory demands. Regression and cognitive computational models of choice behavior showed that with a lower cognitive load, humans are more exploratory than a simulated value-maximizing learner, but under cognitive constraints, they adaptively scale down exploration to maintain exploitation. Thus, while humans are curious, cognitive constraints force people to decrease their strategic exploration in a resource-rational-like manner to focus on harvesting known rewards.
Introduction Global surgery efforts have significantly expanded in the last decade. While an increasing number of general surgery residents are incorporating global surgery experiences and research into their training, few resources are available for residency applicants to evaluate opportunities at programs to which they are applying. Materials and methods A 17-question survey of all general surgery residency program directors (PDs) was conducted by the Global Surgery Student Alliance through emails to the Association of Program Directors in Surgery listserv. PDs indicated if they wished to remain anonymous or include program information in an upcoming online database. Results Two hundred fifty eight general surgery PDs were emailed the survey and 45 (17%) responses were recorded. Twenty eight (62%) programs offered formal global surgery experiences for residents, including clinical rotations, research, and advocacy opportunities. Thirty one (69%) programs were developing a global health center. Forty two (93%) respondents indicated that global surgery education was an important aspect of surgical training. Barriers to global surgery participation included a lack of funding, time constraints, low faculty participation, and minimal institutional interest. Conclusions While most respondents felt that global surgery was important, less than two-thirds offered formal experiences. Despite the significant increase in public awareness and participation in global surgery, these numbers remain low. While this study is limited by a 17% response rate, it demonstrates that more efforts are needed to bolster training, research, and advocacy opportunities for surgical trainees and promote a global perspective on healthcare.
We consider the existence and spectral stability of periodic multi-pulse solutions in Hamiltonian systems which are translation invariant and reversible, for which the fifth-order Korteweg-de Vries equation is a prototypical example. We use Lin's method to construct multi-pulses on a periodic domain, and in particular demonstrate a pitchfork bifurcation structure for periodic double pulses. We also use Lin's method to reduce the spectral problem for periodic multi-pulses to computing the determinant of a block matrix, which encodes both eigenvalues resulting from interactions between neighboring pulses and eigenvalues associated with the essential spectrum. We then use this matrix to compute the spectrum associated with periodic single and double pulses. Most notably, we prove that brief instability bubbles form when eigenvalues collide on the imaginary axis as the periodic domain size is altered. These analytical results are all in good agreement with numerical computations, and numerical timestepping experiments demonstrate that these instability bubbles correspond to oscillatory instabilities.
Siblings describe positive and negative aspects of autism and often assume lifelong support roles. Less is known about cultural influences on sibling relationships. This qualitative study characterizes processes linking siblings’ autism conceptualizations, sibling relationships, and self-concept using a multicultural framework. Siblings (12 Latino/a/x, 9 non-Latino/a/x white) participated. Data were stratified by ethnicity and analyzed using applied thematic analysis. Latino/a/x and non-Latino/a/x siblings described processes linking autism, relationships, and self-concept differently. Latino/a/x siblings emphasized family roles and identified as caregivers and protectors. Non-Latino/a/x siblings emphasized general sensitivity toward individuals who differed from themselves. Findings may reflect cultural differences in familism, caregiving expectations, and autism conceptualizations, thereby illuminating foundations of siblings’ lifelong caregiving roles and highlighting the importance of culturally-sensitive, family-centered care.
In the present review, we consider technology-based methods for training and monitoring counseling skills in behavioral health (i.e., addictions, mental health, and behavioral medicine). We provide an overview of topical foci and design features, as well as review the available research. The Arksey and O'Malley framework for scoping review was used and there were two project phases. First, we reviewed and charted design features and training topics. Second, we reviewed and charted published research evaluating training outcomes. The search process yielded six commercial companies or academic research centers targeting online training of behavioral health counseling skills. These programs could be categorized by an avatar (i.e., computer-generated) or video (i.e., human actor) client interface, as well as by a completely interactive experience (i.e., virtual reality) or an experience with a pre-programmed, branch-logic interaction (i.e., computer simulation). One final company provided monitoring services only, without an explicit training component. The literature in this area is in its nascent stages, with primarily pilot scope and comparatively less progress if contrasted with fields such as general medicine. Online training and monitoring of behavioral health counseling skills is a promising emerging field with positive qualities such as scalability, resource efficiency, and standardization. Future research should emphasize (1) between-group randomized clinical trials, (2) comparisons to standard training practices, and (3) alignment with professional competency standards. Supplementary information: The online version contains supplementary material available at 10.1007/s41347-022-00252-8.
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7,616 members
• Department of Cognitive, Linguistic and Psychological Sciences
• Department of Ecology and Evolutionary Biology
• Brown School of Engineering
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