Campaigning for Judicial Office, 2012

Concerns over the way in which judicial campaigns are conducted have been voiced since the 1970s. Judicial elections are thought to have become rough and tumble contests, featuring increasing campaign expenditures and controversial campaign speech. With the widespread deregulation of judicial candidate campaign speech in the early 2000s, scholars have become increasingly concerned with how judicial candidates campaign. This dissertation examines the role of the media in judicial elections, campaign communication methods used by candidates, how candidates develop campaign messages, controversial campaign speech, the consequences of campaigning, and candidates’ attitudes toward judicial selection reform. Data gathered from a survey of judicial candidates who ran for election in 2012 (n = 490) and follow-up interviews with candidates (n = 35) were used to address the research questions posed by this investigation. Findings reveal a number of areas of concern with judicial elections beyond campaign speech, including lack of media coverage, lack of access to adequate communication channels, and concerns over external group involvement in judicial elections. Controversial speech is rare in judicial campaigns and few candidates favor strong speech regulations, which are viewed as barriers between the office and the public

Gasping in Response to Basic Resuscitation Efforts: Observation in a Swine Model of Cardiac Arrest

Objective. To analyze the effect of basic resuscitation efforts on gasping and of gasping on survival. Methods. This is secondary analysis of a previously reported study comparing continuous chest compressions (CCC CPR) versus chest compressions plus ventilation (30:2 CPR) on survival. 64 swine were randomized to 1 of these 2 basic CPR approaches after either short (3 or 4 minutes) or long (5 or 6 minutes) durations of untreated VF. At 12 minutes of VF, all received the same Guidelines 2005 Advanced Cardiac Life Support. Neurologically status was evaluated at 24 hours. A score of 1 is normal, 2 is abnormal, such as not eating or drinking normally, unsteady gait, or slight resistance to restraint, 3 severely abnormal, where the animal is recumbent and unable to stand, 4 is comatose, and 5 is dead. For this analysis a neurological outcome score of 1 or 2 was classified as “good”, and a score of 3, 4, or 5 was classified as “poor.” Results. Gasping was more likely to continue or if absent, to resume in the animals with short durations of untreated VF before basic resuscitation efforts. With long durations of untreated VF, the frequency of gasping and survival was better in swine receiving CCC CPR. In the absence of frequent gasping, intact survival was rare in the long duration of untreated VF group. Conclusions. Gasping is an important phenomenon during basic resuscitation efforts for VF arrest and in this model was more frequent with CCC-CPR

Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab’)2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation

Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2)

The crystal structure† of LRH-1 ligand binding domain bound to our previously reported agonist 3-(E-oct-4-en-4-yl)-1-phenylamino-2-phenyl-cis-bicyclo[3.3.0]oct-2-ene 5 is described. Two new classes of agonists in which the bridgehead anilino group from our first series was replaced with an alkoxy or 1-ethenyl group were designed, synthesized and tested for activity in a peptide recruitment assay. Both new classes gave very active compounds, particularly against SF-1. Structure-activity studies led to excellent dual-LRH-1 / SF-1 agonists (e.g. RJW100) as well as compounds selective for LRH-1 (RJW101) and SF-1 (RJW102, RJW103). The series based on 1-ethenyl substitution were acid stable, overcoming a significant drawback of our original bridgehead anilino-substituted series. Initial studies on regulation of gene expression in human cell lines showed excellent, reproducible activity at endogenous target genes

Inducing Cross-Clade Neutralizing Antibodies against HIV-1 by Immunofocusing

Background: Although vaccines are important in preventing viral infections by inducing neutralizing antibodies (nAbs), HIV-1 has proven to be a difficult target and escapes humoral immunity through various mechanisms. We sought to test whether HIV-1 Env mimics may serve as immunogens. Methodology/Principal Findings: Using random peptide phage display libraries, we identified the epitopes recognized by polyclonal antibodies of a rhesus monkey that had developed high-titer, broadly reactive nAbs after infection with a simianhuman immunodeficiency virus (SHIV) encoding env of a recently transmitted HIV-1 clade C (HIV-C). Phage peptide inserts were analyzed for conformational and linear homology using computational analysis; some peptides mimicked various domains of the original HIV-C Env, such as conformational V3 loop epitopes and the conserved linear region of the gp120 C-terminus. Next, we devised a novel prime/boost strategy to test the immunogenicity of such phage-displayed peptides and primed mice only once with HIV-C gp160 DNA followed by boosting with mixtures of recombinant phages. Conclusions/Significance: This strategy, which was designed to focus the immune system on a few Env epitopes (immunofocusing), not only induced HIV-C gp160 binding antibodies and cross-clade nAbs, but also linked a conserved HIV Env region for the first time to the induction of nAbs: the C-terminus of gp120. The identification of conserved antige

Translating CDSMP to the Workplace: Results of the Live Healthy Work Healthy Program

Purpose: Report the results of a randomized, controlled trial of Live Healthy, Work Healthy (LHWH), a worksite translation of the Chronic Disease Self-Management Program (CDSMP). Design: 14 worksites were randomly assigned to LHWH, standard CDSMP (usual care) or no-intervention (control) group. Setting: The diverse set of work organizations centered around a rural community in SE US. Subjects: 411 participants completed baseline data with 359 being included in the final analyses. Intervention: LHWH had been adapted to fit the unique characteristics of work organizations. This translated program consists of 15 sessions over 8 weeks and was facilitated by trained lay leaders. Measures: The primary outcomes including health risk, patient-provider communication, quality of life, medical adherence and work performance were collected pretest, posttest (6 mos.) and follow-up (12 mos.). Analysis: Analyses were conducted using latent change score models in a structural equation modeling framework. Results: 79% of participants reported at least one chronic condition with an average of 2.7 chronic conditions reported. Results indicated that LHWH program demonstrated positive changes in a most outcomes including significant exercise (uΔ = 0.89, p \u3c.01), chronic disease self-efficacy (uΔ = 0.63, p \u3c.05), fatigue (uΔ = −1.45, p \u3c.05), stress (uΔ = −0.98, p \u3c.01) and mentally unhealthy days (uΔ = −3.47, p \u3c.001). Conclusions: The translation of LHWH is an effective, low cost, embeddable program that has the potential to improve the health and work life of employees

Gasping during cardiac arrest in humans is frequent and associated with improved survival

The incidence and significance of gasping after cardiac arrest in humans are controversial