Sustainable Options for Division Street

To reflect the Division Vision Coalition\u27s (DVC) desire to promote neighborhood livability through sustainable development, Team Urbanics offered a series of community workshops in May 2004 that explored the concepts of sustainable development. The goals of the Sustainable Options for Division Street workshops were to: Provide DVC with an educational tool that enhances the public’s awareness of sustainable development options Encourage public participation in upcoming redevelopment planning efforts Promote sustainable practices, including environmental protection, economic development, and social equity, and Create a forum for civil discourse, for neighbors to meet neighbors, and for people to learn new things about their community. This project was conducted under the supervision of Deborah Howe, Barry Messer, and Ethan Seltzer

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Interview with Alisa Kane, Office of Sustainable Development, 2006 (audio)

Interview of Alisa Kane by Daniel Woodward at City of Portland Office of Sustainable Development, Oregon on November 30th, 2006. The interview index is available for download

Signal Transducer and Activator of Transcription 3 Control of Human T and B Cell Responses

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated downstream of many key cytokine receptors expressed by lymphocytes. As such, it plays a critical role in regulating B cells as well as CD4+ and CD8+ T cells. Patients with clinically significant immunodeficiency and immune dysregulation resulting from loss-of-function or gain-of-function mutations in STAT3 have been described. These individuals provide insight into the critical role of this transcription factor in the regulation of immune responses and the balance between effective immune protection and autoimmunity

Dissection of T-dependent B cell responses using novel mouse models of primary immunodeficiency

The primary function of T-dependent B cell response is long-lived production of high affinity antibodies. This is a highly regulated process occurring in secondary organs. Insight into the molecular mechanisms that regulate these responses can be gleaned from Mendelian inborn errors of human immunity which cause Primary Immunodeficiency disorders. Autosomal Hyper IgE syndrome caused by loss of function mutations in STAT3 and Activated Phosphotidylinositol-3-OH kinases-?-Syndrome caused by gain-of-function mutations in PIK3CD are two such disorders. Both conditions are associated with clinical features of frequent lower respiratory tract infections with encapsulated organisms and impaired production of specific antibodies. These features suggest that STAT3, a signaling molecule down stream of cytokine receptors, and PI3K?, a signaling molecule downstream of the B cell receptor and co-receptors, are key regulators of the T-dependent B cell response, however, the exact mechanisms underlying the distinct effects of these molecules is poorly understood. To better understand the role of STAT3 and PI3K? on the T dependent B cell response in vivo, novel mouse models of STAT3 loss-of-function and PI3K? gain-of-function were used. STAT3 was found to be a key regulator of multiple aspects of the T dependent B cell response with B cell intrinsic loss-of-function mutations resulting in impaired clonal expansion due to enhanced apoptosis, impaired differentiation into germinal centre B cells, impaired affinity maturation and aberrant class switch recombination with enhanced switching to IgE. T cell intrinsic loss-of-function was associated with reduced T follicular helper cell and germinal centre B cell numbers. The effect of B cell intrinsic PI3K? gain-of-function mutations was more specific with impaired istotype switching and an associated increase in serum IgM. Most importantly, a specific inhibitor of PI3K? was found to completely correct the isotype switching defect due to PI3K? gain-of-function.Both mouse models of human primary immunodeficiency closely recapitulated the defects seen in human disease and have provided new sight in to the regulation of the T-dependent B cell response. In addition, these mouse models of human disease may be useful a tools for the study of precision therapeutics in the future

Mortality and PICU hospitalization among pediatric gunshot wound victims in Chicago

Firearm injury accounts for significant morbidity with high mortality among children admitted to the PICU. Understanding risk factors for PICU admission is an important step toward developing prevention and intervention strategies to minimize the burden of pediatric gunshot wound (GSW) injury. Objectives: The primary objective of this study was to characterize outcomes and the likelihood of PICU admission among children with GSWs. Design setting and participants: Retrospective cohort study of GSW patients 0-18 years old evaluated at the University of Chicago Comer Children\u27s Hospital Pediatric Trauma Center from 2010 to 2017. Main outcomes and measures: Demographic and injury severity measures were acquired from an institutional database. We describe mortality and hospitalization characteristics for the cohort. We used logistic regression models to test the association between PICU admission and patient characteristics. Results: During the 8-year study period, 294 children experienced GSWs. We did not observe trends in overall mortality over time, but mortality for children with GSWs was higher than all-cause PICU mortality. Children 0-6 years old experienced longer hospitalizations compared with children 13-16 years old (5 vs 3 d; p = 0.04) and greater frequency of PICU admission (83.3% vs 52.9%; p = 0.001). Adjusting for severity of illness, children less than 7 years old were four-fold more likely to be admitted to the PICU than children 13-16 years old (aOR range, 3.9-4.6). Conclusions and relevance: Despite declines in pediatric firearm mortality across the United States, mortality did not decrease over time in our cohort and was higher than all-cause PICU mortality. Younger children with GSWs experience longer hospitalizations and require PICU care more often than older children. Our findings suggest that the youngest victims of firearm-related injury may be particularly at-risk of the long-term sequelae of critical illness and injury