How roadway composition matters in analyzing police data on racial profiling

This article argues that roadway composition data is essential to the analysis of police behavior when studying racial profiling of motorists. Police data alone show only the number and proportion of stops of African American and White drivers. They do not show how these numbers relate to the number of African American and White drivers using the roads. Proxy measures, drawn from the number of African American residents or license holders, assume that all roads in the community contain the same proportion The authors acknowledge the generous assistance of the anonymous police department that provided access. The Roadway Observation Study was supported by the Oakland University research committee and Vice-Provost Randy Hanson. We thank our research assistant

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

Differential cellular immunolocalization of renal tumour necrosis factor-α production during ischaemia versus endotoxaemia

Both renal ischaemia and endotoxaemia provoke renal dysfunction and cellular injury. Although the clinical manifestation of each insult is similar (global renal dysfunction), ischaemia and endotoxaemia induce different patterns of cellular injury. Tumour necrosis factor-α (TNF-α) has been implicated in both types of renal injury; however, it remains unknown whether differential cellular TNF-α expression accounts for these changes. We hypothesized that renal glomerular cells and tubular cells differentially express TNF-α in response to ischaemia compared with endotoxaemia. To investigate this hypothesis, male Sprague–Dawley rats were anaesthetized and exposed to various time-periods of renal ischaemia, with or without reperfusion (sham operation=negative control), or lipopolysaccharide (LPS) 0·5 mg/kg intraperitoneally (i.p.). The kidneys were harvested following renal injury, and rat TNF-α protein expression was determined (by enzyme-linked immunosorbent assay), as were TNF-α bioactivity (by WEHI-164 cell clone cytotoxicity assay) and TNF-α cellular localization (by immunohistochemistry). TNF-α protein expression and TNF-α bioactivity peaked following 1 hr of ischaemia and 2 hr of reperfusion (48 ± 11 pg/mg of protein, P < 0·05, and 12 ± 0·5 × 10(−3) units/mg of protein, P < 0·05, respectively). The concentration of TNF-α increased to a similar extent following exposure to LPS; however, while TNF-α production following ischaemia-reperfusion injury localized predominantly to renal tubular epithelial cells, animals exposed to LPS demonstrated a primarily glomerular distribution of TNF-α production. Hence, the cellular localization of renal TNF-α production appears to be injury specific, i.e. renal tubular cells are the primary source of TNF-α following an ischaemic insult, whereas LPS induces glomerular TNF-α production. The cellular source of TNF-α following different insults may have therapeutic implications for targeted inhibition of TNF-α production