Assessing nonresponse bias at follow-up in a large prospective cohort of relatively young and mobile military service members

<p>Abstract</p> <p>Background</p> <p>Nonresponse bias in a longitudinal study could affect the magnitude and direction of measures of association. We identified sociodemographic, behavioral, military, and health-related predictors of response to the first follow-up questionnaire in a large military cohort and assessed the extent to which nonresponse biased measures of association.</p> <p>Methods</p> <p>Data are from the baseline and first follow-up survey of the Millennium Cohort Study. Seventy-six thousand, seven hundred and seventy-five eligible individuals completed the baseline survey and were presumed alive at the time of follow-up; of these, 54,960 (71.6%) completed the first follow-up survey. Logistic regression models were used to calculate inverse probability weights using propensity scores.</p> <p>Results</p> <p>Characteristics associated with a greater probability of response included female gender, older age, higher education level, officer rank, active-duty status, and a self-reported history of military exposures. Ever smokers, those with a history of chronic alcohol consumption or a major depressive disorder, and those separated from the military at follow-up had a lower probability of response. Nonresponse to the follow-up questionnaire did not result in appreciable bias; bias was greatest in subgroups with small numbers.</p> <p>Conclusions</p> <p>These findings suggest that prospective analyses from this cohort are not substantially biased by non-response at the first follow-up assessment.</p

How does one become spiritual? The Spiritual Modeling Inventory of Life Environments (SMILE)

We report psychometric properties, correlates and underlying theory of the Spiritual Modeling Index of Life Environments (SMILE), a measure of perceptions of spiritual models, defined as everyday and prominent people who have functioned for respondents as exemplars of spiritual qualities, such as compassion, self-control, or faith. Demographic, spiritual, and personality correlates were examined in an ethnically diverse sample of college students from California, Connecticut, and Tennessee (N=1010). A summary measure of model influence was constructed from perceived models within family, school, religious organization, and among prominent individuals from both tradition and media. The SMILE, based on concepts from Bandura\u27s (1986) Social Cognitive Theory, was well-received by respondents. The summary measure demonstrated good 7-week test/retest reliability (r=.83); patterns of correlation supporting convergent, divergent, and criterion-related validity; demographic differences in expected directions; and substantial individual heterogeneity. Implications are discussed for further research and for pastoral, educational, and health-focused interventions

Evidence That a Lipolytic Enzyme—Hematopoietic-Specific Phospholipase C-β2—Promotes Mobilization of Hematopoietic Stem Cells by Decreasing Their Lipid Raft-Mediated Bone Marrow Retention and Increasing the Promobilizing Effects of Granulocytes

Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs

DCs Pulsed with Novel HLA-A2-Restricted CTL Epitopes against Hepatitis C Virus Induced a Broadly Reactive Anti-HCV-Specific T Lymphocyte Response

OBJECTIVE: To determine the capacity of dendritic cells (DCs) loaded with single or multiple-peptide mixtures of novel hepatitis C virus (HCV) epitopes to stimulate HCV-specific cytotoxic T lymphocyte (CTL) effector functions. METHODS: A bioinformatics approach was used to predict HLA-A2-restricted HCV-specific CTL epitopes, and the predicted peptides identified from this screen were synthesized. Subsequent IFN-γ ELISPOT analysis detected the stimulating function of these peptides in peripheral blood mononuclear cells (PBMCs) from both chronic and self-limited HCV infected subjects (subjects exhibiting spontaneous HCV clearance). Mature DCs, derived in vitro from CD14(+) monocytes harvested from the study subjects by incubation with appropriate cytokine cocktails, were loaded with novel peptide or epitope peptide mixtures and co-cultured with autologous T lymphocytes. Granzyme B (GrB) and IFN-γ ELISPOT analysis was used to test for epitope-specific CTL responses. T-cell-derived cytokines contained in the co-cultured supernatant were detected by flow cytometry. RESULTS: We identified 7 novel HLA-A2-restricted HCV-specific CTL epitopes that increased the frequency of IFN-γ-producing T cells compared to other epitopes, as assayed by measuring spot forming cells (SFCs). Two epitopes had the strongest stimulating capability in the self-limited subjects, one found in the E2 and one in the NS2 region of HCV; five epitopes had a strong stimulating capacity in both chronic and self-limited HCV infection, but were stronger in the self-limited subjects. They were distributed in E2, NS2, NS3, NS4, and NS5 regions of HCV, respectively. We also found that mDCs loaded with novel peptide mixtures could significantly increase GrB and IFN-γ SFCs as compared to single peptides, especially in chronic HCV infection subjects. Additionally, we found that DCs pulsed with multiple epitope peptide mixtures induced a Th1-biased immune response. CONCLUSIONS: Seven novel and strongly stimulating HLA-A2-restricted HCV-specific CTL epitopes were identified. Furthermore, DCs loaded with multiple-epitope peptide mixtures induced epitope-specific CTLs responses

Conservation of Complex Nuclear Localization Signals Utilizing Classical and Non-Classical Nuclear Import Pathways in LANA Homologs of KSHV and RFHV

ORF73 latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS) in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG)-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin β1 in a RanGTP-sensitive manner and serves as an NLS in the importin β1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR)-rich bipartite motif that binds directly to multiple members of the importin α family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin α/β-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an increased ability to interact with different nuclear components in its multifunctional role to maintain viral latency

Flash Flood simulation and valve behavior of Mytilus galloprovincialis measured with Hall sensors

Mussels close their shell as a protective strategy and the quantification of this behavioral marker may represent an alarm signal when they are exposed to environmental stressors. In the present study, we investigated the ability of the Mediterranean mussel Mytilus galloprovincialis to recover and then the resilience or inertia of valve activity after a pulsing exposition to diverse levels of salinity (5, 10, 20 and 35 PSU as reference value). The trial simulated an event of drastic and sudden reduction of seawater salinity thus mimicking an event of Flash Flood from intense rain. Valve gaping and movements were measured in continuous cycle for ten days using a customized magneto-electric device which uses Hall sensors. Results showed that under normal conditions of salinity (35 PSU) the general pattern of valve movements was a continuously open state with sporadic spikes indicating a closing motion. At salinity of 5 PSU mussels reacted by closing their valves, leading to a 77% mortality on the fourth day. At salinity of 10 PSU animals were observed with closed valves for the entire duration of the exposure and no mortality occurred, they showed a significant reduction in the valve activity once the reference value of salinity was re-established. In contrast, salinity of 20 PSU did not trigger a significant behavioral response. Interestingly, there no define rhythms of valve movements were recorded during salinity challenges