The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities

Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Peptide-Modified Albumin Carrier Explored as a Novel Strategy for a Cell-Specific Delivery of Interferon Gamma To Treat Liver Fibrosis

Excessive accumulation of the extracellular matrix proteins primarily produced by activated hepatic stellate cells (HSC) leads to liver fibrosis. To date, no successful therapeutic intervention is available for the treatment of this disease. Platelet derived growth factor beta receptor (PDGF beta R) is highly upregulated on disease-inducing activated HSC and thus can be used for delivery of antifibrotic drugs to increase therapeutic efficacy with reduced adverse effects. Interferon gamma (IFN gamma) has been recognized as a potent antifibrotic cytokine; however, poor pharmacokinetics and side effects due to frequent administration have limited its clinical use. For HSC-specific delivery, a PDGF beta R-specific drug delivery carrier (PPB-HSA) was developed by modifying albumin with PDGF beta R-recognizing cyclic peptides. Subsequently, IFN gamma was conjugated to PPB-HSA via bifunctional PEG linkers to synthesize PPB-HSA-PEG-IFN gamma. In vitro, PPB-HSA-PEG-IFN gamma retained complete biological activity similar to unmodified IFN gamma and showed PDGF beta R-specific binding to human HSC and primary culture-activated rat HSC. In TGF beta-stimulated mouse fibroblasts and human HSC, PPB-HSA-PEG-IFN gamma induced significant reduction in crucial fibrotic parameters. In vivo, the conjugate rapidly accumulated into PDGF beta R-expressing HSC in fibrotic livers and activated IFN gamma-mediated pstat1 alpha signaling pathway. Furthermore, in a CCl(4)-induced acute liver injury model in mice, treatment with HSC-targeted IFN gamma strongly ameliorated hepatic fibrogenesis by inducing significant reduction (about 60%; p <0.01) in collagen I and alpha-SMA expression as well as enhanced fibrolysis (increased MMP/TIMP ratio; p <0.05) while free unmodified IFN gamma was ineffective. Furthermore, in contrast to free native IFN gamma, the conjugate did not induce macrophage infiltration and IL-1 beta expression in the liver. In conclusion, these data demonstrate the enhanced antifibrotic efficacy and reduced off-target effects of PPB-HSA-PEG-IFN gamma conjugate showing the potential of cell-specific targeting of IFN gamma for the treatment of liver fibrosis

Early intensive care sedation predicts long-term mortality in ventilated critically ill patients

Rationale: Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome. Objectives: To investigate the relationships between early sedation and time to extubation, delirium, and hospital and 180-day mortality among ventilated critically ill patients in the intensive care unit (ICU). Methods: Multicenter (25 Australia and New Zealand hospitals) prospective longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients ventilated and sedated 24 hours or more. We assessed administration of sedative agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We used multivariable Cox regression to quantify relationships between early deep sedation (RASS, -3 to -5) and patients' outcomes. Measurements and Main Results: We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR, 1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01-1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19). Conclusions: Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies