African American Caregivers' Racial Socialization Profiles Across Adolescents' Transition to High School: Associations with Gender, Racial Identity, Interracial Contact, and Racial Discrimination

In a cross-sectional sample of 598 African American caregivers and adolescents, this dissertation investigates whether and how the racial socialization messages of Black caregivers change as their children transition from middle to high school. I used latent class analysis implemented by Mplus to identify racial socialization clusters at three different time points (i.e., seventh grade, eighth grade, and ninth grade). Racial socialization clusters were comprised of three types of racial socialization messages (i.e., Navigation Capital messages, Black Cultural Immersion, and Racial Barrier messages). Navigation Capital messages represent a new racial socialization category that aligns with Yosso’s (2005) navigation capital from her model of community cultural wealth, while Black Cultural Immersion and Racial Barrier socialization messages align with previously researched constructs (e.g., White-Johnson et al., 2010). For caregivers of adolescents in the seventh grade, I identified five clusters of caregiver-reported racial socialization patterns: High Multifaceted, Black Navigation Capital, Low Multifaceted, Egalitarian Navigation Capital, and Barrier Immersion. Caregivers with adolescents in the eighth grade and ninth grade had the same five clusters of racial socialization patterns: High Multifaceted, Black Navigation Capital, Low Multifaceted, Infrequent, and Moderate Multifaceted. I also used a series of analyses of variance (ANOVAs) in SPSS to conduct an examination of how adolescent gender, caregiver racial identity, family interracial contact, caregiver and adolescent reports of racial discrimination, and caregiver and adolescent reported quality of communication related to caregiver cluster membership. Findings indicate that racial centrality, experiences of racial discrimination, and quality of communication were predictive of caregiver racial socialization cluster membership, especially for caregivers with adolescents in the seventh and ninth grades. In the seventh and ninth grades, caregivers with the highest reports of racial centrality were members of the High Multifaceted cluster (i.e., above average score in Navigation Capital, BCI, and Racial Barrier messages). An important contribution of this dissertation is the exploration of how different types of racial discrimination experiences (i.e., Invisible/Outsider, Criminal, Harassment, Unintelligent, Other) could explain caregiver cluster membership. Racial discriminatory experiences of being treated like a criminal and harassed were particularly predictive of cluster membership. Caregivers in the seventh grade High Multifaceted cluster reported significantly more experiences of being treated like a criminal than caregivers in the seventh grade Egalitarian Navigation Capital cluster. In comparison to caregivers in the ninth grade Black Navigation Capital cluster, caregivers in the ninth grade High Multifaceted cluster also reported more experiences of being harassed, being treated as criminal, and being treated as if they were unintelligent. From a developmental perspective, my results suggest that a) caregivers move towards race salience racial socialization patterns (i.e., High Multifaceted Cluster) and away from patterns in which racial barrier messages are minimized (i.e., Black Navigation Capital Cluster) over time and b) substantial shifts in racial socialization patterns may happen before the transition to high school.PhDEducation & PsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169667/1/asyaah_1.pd

Adherence enables Neisseria gonorrhoeae to overcome zinc limitation imposed by nutritional immunity proteins

Neisseria gonorrhoeae (Gc) must overcome the limitation of metals such as zinc to colonize mucosal surfaces in its obligate human host. While the zinc-binding nutritional immunity proteins calprotectin (S100A8/A9) and psoriasin (S100A7) are abundant in human cervicovaginal lavage fluid, Gc possesses TonB-dependent transporters TdfH and TdfJ that bind and extract zinc from the human version of these proteins, respectively. Here we investigated the contribution of zinc acquisition to Gc infection of epithelial cells of the female genital tract. We found that TdfH and TdfJ were dispensable for survival of strain FA1090 Gc that was associated with Ect1 human immortalized epithelial cells, when zinc was limited by calprotectin and psoriasin. In contrast, suspension-grown bacteria declined in viability under the same conditions. Exposure to murine calprotectin, which Gc cannot use as a zinc source, similarly reduced survival of suspension-grown Gc, but not Ect1-associated Gc. We ruled out epithelial cells as a contributor to the enhanced growth of cell-associated Gc under zinc limitation. Instead, we found that attachment to glass was sufficient to enhance bacterial growth when zinc was sequestered. We compared the transcriptional profiles of WT Gc adherent to glass coverslips or in suspension, when zinc was sequestered with murine calprotectin or provided in excess, from which we identified open reading frames that were increased by zinc sequestration in adherent Gc. One of these, ZnuA, was necessary but not sufficient for survival of Gc under zinc-limiting conditions. These results show that adherence protects Gc from zinc-dependent growth restriction by host nutritional immunity proteins

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II\ue2\u80\u93IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56\uc2\ub76 [SEM 4\uc2\ub75] vs 68\uc2\ub73 [4\uc2\ub75]; rank-based treatment difference \ue2\u88\u9211\uc2\ub77, 95% CI \ue2\u88\u9224\uc2\ub73 to 0\uc2\ub796; p=0\uc2\ub70698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals