Horatio Alger: The Persistence of a Ghetto Social Welfare Institution

Despite the riots, radical movements and demands for community controls of the 1960\u27s, social scientists and social workers have noted the perserverance of many non-radical, traditional institutions in ghetto neighborhoods. Some of these institutions, like settlement houses, still advance the ideas of hard work, hoensty, competition, and individual achievement which are at the heart of the American dream. These institutions were often around long before the War on Poverty and appear likely to last long after its end. They, therefore, seem to be a reliable potential source of aid for many ghetto residents. The question at the heart of this paper is whether there is any contradiction between the more or less permanent place of social welfare institutions in a ghetto community and the goal of changing and improving that same neighborhood. How have these traditional organizations been able to survive during a period of heightened social consciousness and political action? What accommodations, if any,have they had to make? and what does this perserverance indicate about the political culture in the ghetto and the possibility of significant, even radical, change? Our answer to these issues will come from looking at the ideology, staff, budget, and Board of Trustees of one social welfare institution in New York: The Boys\u27 Club

Horatio Alger: The Persistence of a Ghetto Social Welfare Institution

Despite the riots, radical movements and demands for community controls of the 1960\u27s, social scientists and social workers have noted the perserverance of many non-radical, traditional institutions in ghetto neighborhoods. Some of these institutions, like settlement houses, still advance the ideas of hard work, hoensty, competition, and individual achievement which are at the heart of the American dream. These institutions were often around long before the War on Poverty and appear likely to last long after its end. They, therefore, seem to be a reliable potential source of aid for many ghetto residents. The question at the heart of this paper is whether there is any contradiction between the more or less permanent place of social welfare institutions in a ghetto community and the goal of changing and improving that same neighborhood. How have these traditional organizations been able to survive during a period of heightened social consciousness and political action? What accommodations, if any,have they had to make? and what does this perserverance indicate about the political culture in the ghetto and the possibility of significant, even radical, change? Our answer to these issues will come from looking at the ideology, staff, budget, and Board of Trustees of one social welfare institution in New York: The Boys\u27 Club

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome.

Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it

The numbers of differentially expressed genes with a p-value less than 0.05 are shown for each comparison.

See S1–S4 Tables for full lists of significant differentially expressed genes.</p

RNA-seq analysis shows differentially expressed genes between proband and control groups.

A. T-SNE shows clusters based on hypoxia treatment and whether the sample is from a proband or a control. B. Heatmap of significant (pTable 1.</p

g:Profiler results from the analysis of 58 genes differentially expressed in four proband fibroblast lines cultured at normoxia compared to three control fibroblast lines cultured at normoxia.

Analysis was performed using the default settings and selecting the Ensembl ID with the most annotations for each gene name. The p-value cut-off was 0.05 after g:SCS significance adjustment. (PDF)</p

Primer pairs designed for genomic DNA amplification and Sanger sequencing of candidate variants.

(PDF)</p

g:Profiler results from the analysis of 28 genes differentially expressed in three proband fibroblast lines cultured at hypoxia compared to three control fibroblast lines cultured at hypoxia.

Analysis was performed using the default settings and selecting the Ensembl ID with the most annotations for each gene name. The p-value cut-off was 0.05 after g:SCS significance adjustment. (PDF)</p