Use of a modified delphi process for establishing occupational exposure limits in support of health surveillance for space travelers

On-orbit exposures can come from numerous factors related to the space environment as evidenced by almost 50 years of environmental samples collected for water analysis, air analysis, radiation analysis, and physiologic parameters. For astronauts and spaceflight participants the occupational exposures can be very different from those experienced by workers performing similar tasks in workplaces on Earth, because the duration of the exposure could be continuous for very long orbital, and eventually interplanetary, missions. The establishment of long-term exposure standards is vital to controlling the quality of the spacecraft environment over long periods. NASA often needs to update and revise its prior exposure standards (Spacecrafts Maximum Allowable Concentrations (SMACs)). Traditional standards-setting processes are often lengthy, so a more rapid method to review and establish standards would be a substantial advancement in this area. This project investigates use of the Delphi method for this purpose. ^ In order to achieve the objectives of this study a modified Delphi methodology was tested in three trials executed by doctoral students and a panel of experts in disciplines related to occupational safety and health. During each test/trial modifications were made to the methodology. Prior to submission of the Delphi Questionnaire to the panel of experts a pilot study/trial was conducted using five doctoral students with the goals of testing and adjusting the Delphi questionnaire to improve comprehension, work out any procedural issues and evaluate the effectiveness of the questionnaire in drawing the desired responses. The remainder of the study consisted of two trials of the Modified Delphi process using 6 chemicals that currently have the potential of causing occupational exposures to NASA astronauts or spaceflight participants. To assist in setting Occupational Exposure Limits (OEL), the expert panel was established consisting of experts from academia, government and industry. Evidence was collected and used to create close-ended questionnaires which were submitted to the Delphi panel of experts for the establishment of OEL values for three chemicals from the list of six originally selected (trial 1). Once the first Delphi trial was completed, adjustments were made to the Delphi questionnaires and the process above was repeated with the remaining 3 chemicals (trial 2). ^ Results indicate that experience in occupational safety and health and with OEL methodologies can have a positive effect in minimizing the time experts take in completing this process. Based on the results of the questionnaires and comparison of the results with the SMAC already established by NASA, we conclude that use of the Delphi methodology is appropriate for use in the decision-making process for the selection of OELs.^

The type-A horizontal cell: GABAergic characteristics and role in development of the outer plexiform layer

Morphological analysis of neonatal rabbit retina suggests that the type-A horizontal cell acts as the pioneer cell for development of the OPL. It is the first mature element of the OPL, and it forms the infrastructure upon which the OPL accrues. The role of type-A horizontal cells in influencing postnatal development of the OPL was examined.^ GABAergic characteristics of the type-A horizontal cell were defined. The type-A horizontal cell was found to possess two more GABAergic characteristics in addition to those previously demonstrated, during a short period in early postnatal development: endogenous stores of GABA and the GABA precursor, glutamate. Lesioning the type-A horizontal cell resulted in their permanent loss in addition to the disappearance of cone terminals and a dramatic increase in rod terminals within the OPL. Thus the type-A cells are not a necessary prerequisite for positioning the OPL in postnatal development, but may be necessary for establishment of the normal photoreceptor mosaic.^ Since type-A horizontal cells possess a number of GABAergic qualities during the period of cone photoreceptor cell differentiation, and there are reports of GABA's trophic action in other developing neuronal systems; the role that GABAergic type-A horizontal cells play in directing photoreceptor differentiation was examined.^ Disrupting effects of GABA-A receptor antagonists indicate that type-A horizontal cells act as postsynaptic targets for the growing cone terminals of photoreceptor cells. These trophic or synaptic interactions may involve GABA-A receptors activated by GABA released from horizontal cells. These findings are consistent with the hypothesis that type-A horizontal cells act as pioneering cells in directing the postnatal development of the OPL.^ These studies offer an in depth analysis of the structural and chemical relationship between type-A horizontal cells and other elements of the OPL from which the roles of type-A horizontal cells and the GABA system in development can be defined. They contribute to our knowledge of both structural and GABAergic mechanisms involved in central nervous system development. ^

Genetic and functional analyses of cell division proteins FtsZ and FtsA in Escherichia coli

In the current model for bacterial cell division, the FtsZ protein forms a ring that marks the division plane, creating a cytoskeletal framework for the subsequent action of other essential division proteins such as FtsA and ZipA. The putative protein complex ultimately generates the division septum. The essential cell division protein FtsZ is a functional and structural homolog of eukaryotic tubulin, and like tubulin, FtsZ hydrolyzes GTP and self-assembles into protein filaments in a strictly GTP-dependent manner. FtsA shares sequence similarity with members of the ATPase superfamily that include actin, but its actual function remains unknown. To test the division model and elucidate functions of the division proteins, this dissertation primarily focuses on the analysis of FtsZ and FtsA in Escherichia coli. ^ By tagging with green fluorescent protein, we first demonstrated that FtsA also exhibits a ring-like structure at the potential division site. The localization of FtsA was dependent on functional FtsZ, suggesting that FtsA is recruited to the septum by the FtsZ ring. In support of this idea, we showed that FtsA and FtsZ directly interact. Using a novel E. coli in situ assay, we found that the FtsA-FtsZ interaction appears to be species-specific, although an interspecies interaction could occur between FtsA and FtsZ proteins from two closely related organisms. In addition, mutagenesis of FtsA revealed that no single domain is solely responsible for its septal localization or interaction with FtsZ. To explore the function of FtsA, we purified FtsA protein and demonstrated that it has ATPase activity. Furthermore, purified FtsA stimulates disassembly of FtsZ polymers in a sedimentation assay but does not affect GTP hydrolysis of FtsZ. This result suggests that in the cell, FtsA may function similarly in regulating dynamic instability of the FtsZ ring during the cell division process. ^ To elucidate the structure-function relationship of FtsZ, we carried out thorough genetic and functional analyses of the mutagenized FtsZ derivatives. Our results indicate that the conserved N-terminal domain of FtsZ is necessary and sufficient for FtsZ self-assembly and localization. Moreover, we discovered a critical role for an extreme C-terminal domain of FtsZ that consists of only 12 residues. Truncated FtsZ derivatives lacking this domain, though able to polymerize and localize, are defective in ring formation in vivo as well as interaction with FtsA and ZipA. Alanine scanning mutagenesis of this region pinpointed at least five residues necessary for the function of FtsZ. Studies of protein levels and protein-protein interactions suggested that these residues may be involved in regulating protein stability and/or FtsZ-FtsA interactions. Interestingly, two of the point mutants exhibited dominant-negative phenotypes. ^ In summary, results from this thesis work have provided additional support for the division machinery model and will contribute to a better understanding of the coordinate functions of FtsA and FtsZ in the cell division process. ^

Factors that affect non-adherence to first line antiretroviral medications among HIV infected children and adolescents in Botswana

The aims of the study were to determine the prevalence of and factors that affect non-adherence to first line antiretroviral (ARV) medications among HIV infected children and adolescents in Botswana. The study used secondary data from Botswana-Baylor Children's Clinical Center of Excellence for the period of June 2008 to February 10th, 2010. The study design was cross-sectional and case-comparison between non-adherent and adherent participants was used to examine the effects of socio-demographic and medication factors on non-adherence to ARV medications. A case was defined as non-adherent child with adherence level < 95% based on pill count and measurement of liquid formulations. The comparison group consisted of children with adherence levels ≥95%.^ A total of 842 participants met the eligibility criteria for determination of the prevalence of non-adherence and 338 participants (169 cases and 169 individuals) were used in the analysis to estimate the effects of factors on non-adherence. ^ Univariate and multivariable logistic regression were used to estimate the association between non-adherence (outcome) and socio-demographic and medication factors (exposures). The prevalence of non-adherence for participants on first line ARV medications was 20.0% (169/842).^ Increase in age (OR (95% CI): 1.10 (1.04–1.17) p = 0.001) was associated with nonadherence, while increase in number of caregivers (OR (95% CI): 0.72 (0.56–0.93) p = 0.01) and increase in number of monthly visits (OR (95% CI): 0.92 (0.86–0.99) p = 0.02), were associated with good adherence in both the unadjusted and the adjusted models. For the categorical variables, having more than two caregivers (OR (95% CI): 0.66 (0.28–0.84), p = 0.002) was associated with good adherence even in the adjusted model. ^ Conclusion. The prevalence of non-adherence to antiretroviral medicines among the study population was estimated to be 20.0%. In previous studies, adherence levels of ≥ 95% have been associated with better clinical outcomes and suppression of virus to prevent development of resistance. Older age, fewer numbers of caregivers and fewer monthly visits were associated with non-adherence. Strategies to improve and sustain adherence especially among older children are needed. The role of caregivers and social support should be investigated further.^

Cross-culture perspectives on fear of HIV disease and AIDS in health care workers

Health care workers have been known to carry into the workplace a variety of judgmental and negative attitudes towards their patients. In no other area of patient care has this issue been more pronounced as in the management of patients with AIDS. Health care workers have refused to treat or manage patients with AIDS and have often treated them more harshly than identically described leukemia patients. Some health care institutions have simply refused to admit patients with AIDS and even recent applicants to medical colleges and schools of nursing have indicated a preference for schools in areas with low prevalence of HIV disease. Since the attitudes of health care workers do have significant consequences on patient management, this study was carried out to determine the differences in clinical practice in Nigeria and the United States of America as it relates to knowledge of a patient's HIV status, determine HIV prevalence and culture in each of the study sites and how they impact on infection control practices, determine the relationship between infection control practices and fear of AIDS, and also determine the predictors of safe infection control practices in each of the study sites.^ The study utilized the 38-item fear of AIDS scale and the measure of infection control questionnaire for its data. Questionnaires were administered to health care workers at the university teaching hospital sites of Houston, Texas and Calabar in Nigeria. Data was analyzed using a chi-square test, and where appropriate, a student t-tests to establish the demographic variables for each country. Factor analysis was done using principal components analysis followed by varimax rotation to simple structure. The subscale scores for each study site were compared using t-tests (separate variance estimates) and utilizing Bonferroni adjustments for number of tests. Finally, correlations were carried out between infection control procedures and fear of AIDS in each study site using Pearson-product moment correlation coefficients.^ The study revealed that there were five dimensions of the fear of AIDS in health care workers, namely fear of loss of control, fear of sex, fear of HIV infection through blood and illness, fear of death and medical interventions and fear of contact with out-groups. Fear of loss of control was the primary area of concern in the Nigerian health care workers whereas fear of HIV infection through blood and illness was the most important area of AIDS related feats in United States health care workers. The study also revealed that infection control precautions and practices in Nigeria were based more on normative and social pressures whereas it was based on knowledge of disease transmission, supervision and employee discipline in the United States, and thus stresses the need for focused educational programs in health care settings that emphasize universal precautions at all times and that are sensitive to the cultural nuances of that particular environment. ^

Interrelationships between the structural and functional aspects of social relationships, comorbidity and health related quality of life in breast cancer survivors

It is widely acknowledged in theoretical and empirical literature that social relationships, comprising of structural measures (social networks) and functional measures (perceived social support) have an undeniable effect on health outcomes. However, the actual mechanism of this effect has yet to be clearly understood or explicated. In addition, comorbidity is found to adversely affect social relationships and health related quality of life (a valued outcome measure in cancer patients and survivors). ^ This cross sectional study uses selected baseline data (N=3088) from the Women's Healthy Eating and Living (WHEL) study. Lisrel 8.72 was used for the latent variable structural equation modeling. Due to the ordinal nature of the data, Weighted Least Squares (WLS) method of estimation using Asymptotic Distribution Free covariance matrices was chosen for this analysis. The primary exogenous predictor variables are Social Networks and Comorbidity; Perceived Social Support is the endogenous predictor variable. Three dimensions of HRQoL, physical, mental and satisfaction with current quality of life were the outcome variables. ^ This study hypothesizes and tests the mechanism and pathways between comorbidity, social relationships and HRQoL using latent variable structural equation modeling. After testing the measurement models of social networks and perceived social support, a structural model hypothesizing associations between the latent exogenous and endogenous variables was tested. The results of the study after listwise deletion (N=2131) mostly confirmed the hypothesized relationships (TLI, CFI >0.95, RMSEA = 0.05, p=0.15). Comorbidity was adversely associated with all three HRQoL outcomes. Strong ties were negatively associated with perceived social support; social network had a strong positive association with perceived social support, which served as a mediator between social networks and HRQoL. Mental health quality of life was the most adversely affected by the predictor variables. ^ This study is a preliminary look at the integration of structural and functional measures of social relationships, comorbidity and three HRQoL indicators using LVSEM. Developing stronger social networks and forming supportive relationships is beneficial for health outcomes such as HRQoL of cancer survivors. Thus, the medical community treating cancer survivors as well as the survivor's social networks need to be informed and cognizant of these possible relationships. ^