A Case of Ability and Disability: What Managers Must Know About the ADA

This teaching exercise addresses a relatively neglected area of diversity, the employment of persons with disabilities. In the first part of the two-stage exercise, students are required to make a hiring decision based on a case that includes candidates who are disabled. This decision raises issues concerning the legal and ethical responsibilities of a hiring manager and uncovers some of the myths concerning candidates with disabilities. The case is subsequently used to anchor a lecture on essential information every manager should know about the Americans with Disabilities Act (ADA) and disability in the workplace. As a result of this exercise, students improved their knowledge of the ADA and the vocabulary associated with the Act, and recognized unfounded attitudes that can limit the employment prospects of persons with disabilities

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

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

The Necessity of α4* Nicotinic Receptors in Nicotine-Driven Behaviors: Dissociation Between Reinforcing and Motor Effects of Nicotine

Here we utilize a mouse line with a targeted deletion of the α4 subunit (α4−/− mice), to investigate the role of α4* nAChRs in reinforcing and locomotor effects of nicotine. Within a conditioned place preference paradigm, both α4−/− mice and wild-type (WT) littermates showed a similar place preference to nicotine (0.5 mg/kg i.p.) conditioning. When assessed for operant intravenous self-administration of nicotine (0.05 mg/kg/infusion), α4−/− mice did not differ from their WT littermates in self-administration behavior. To further examine a modulatory role for α4* nAChRs in the reinforcing effects of nicotine, a transgenic mouse with a point mutation of the α4 subunit (α4-S248F) that renders increased sensitivity to low dose nicotine, was assessed for nicotine self-administration over a range of doses. At higher doses examined (0.05 and 0.07 mg/kg/infusion) there was no difference in intravenous nicotine self-administration; however, when mice were offered a lower dose of nicotine (0.03 mg/kg/infusion), α4-S248F mice showed greater nicotine intake than controls. Acute administration of 0.5 mg/kg nicotine caused significant locomotor depression in WT mice but α4−/− mice instead showed significant hyperactivity. Following chronic, intermittent administration of this dose of nicotine only WT mice displayed significant tolerance. Analogous experiments utilizing administration of the nicotinic antagonist mecamylamine in WT mice confirmed a dissociation between the putative nicotinic receptor subtypes required for mediating psychomotor and reinforcing effects of nicotine. These data demonstrate a necessary role for α4* nAChRs in the locomotor depressant effect of nicotine but not the reinforcing effects that support ongoing self-administration of nicotine

α-Conotoxin MII-Sensitive Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Shell Regulate Progressive Ratio Responding Maintained by Nicotine

β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; asterisk (*) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of α-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of α-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation