17 resultados para longitudinal analyses

em Duke University


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Sexual risk behavior among young adults is a serious public health concern; 50% will contract a sexually transmitted infection (STI) before the age of 25. The current study collected self-report personality and sexual history data, as well as neuroimaging, experimental behavioral (e.g., real-time hypothetical sexual decision making data), and self-report sexual arousal data from 120 heterosexual young adults ages 18-26. In addition, longitudinal changes in self-reported sexual behavior were collected from a subset (n = 70) of the participants. The primary aims of the study were (1) to predict differences in self-report sexual behavior and hypothetical sexual decision-making (in response to sexually explicit audio-visual cues) as a function of ventral striatum (VS) and amygdala activity, (2) test whether the association between sexual behavior/decision-making and brain function is moderated by gender, self-reported sexual arousal, and/or trait-level personality factors (i.e., self-control, impulsivity, and sensation seeking) and (3) to examine how the main effects of neural function and interaction effects predict sexual risk behavior over time. Our hypotheses were mostly supported across the sexual behavior and decision-making outcome variables, such that neural risk phenotypes (heightened reward-related ventral striatum activity coupled with decreased threat-related amygdala activity) were associated with greater lifetime sexual partners at baseline measured and over time (longitudinal analyses). Impulsivity moderated the relationship between neural function and self-reported number of sexual partners at baseline and follow up measures, as well as experimental condom use decision-making. Sexual arousal and sensation seeking moderated the relationship between neural function and baseline and follow up self-reports of number of sexual partners. Finally, unique gender differences were observed in the relationship between threat and reward-related neural reactivity and self-reported sexual risk behavior. The results of this study provide initial evidence for the potential role for neurobiological approaches to understanding sexual decision-making and risk behavior. With continued research, establishing biomarkers for sexual risk behavior could help inform the development of novel and more effective individually tailored sexual health prevention and intervention efforts.

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Using data from a longitudinal study of community-dwelling older adults, we analyzed the most extensive set of known correlates of PTSD symptoms obtained from a single sample to examine the measures' independent and combined utility in accounting for PTSD symptom severity. Fifteen measures identified as PTSD risk factors in published meta-analyses and 12 theoretically and empirically supported individual difference and health-related measures were included. Individual difference measures assessed after the trauma, including insecure attachment and factors related to the current trauma memory, such as self-rated severity, event centrality, frequency of involuntary recall, and physical reactions to the memory, accounted for symptom severity better than measures of pre-trauma factors. In an analysis restricted to prospective measures assessed before the trauma, the total variance explained decreased from 56% to 16%. Results support a model of PTSD in which characteristics of the current trauma memory promote the development and maintenance of PTSD symptoms.

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How do infants learn word meanings? Research has established the impact of both parent and child behaviors on vocabulary development, however the processes and mechanisms underlying these relationships are still not fully understood. Much existing literature focuses on direct paths to word learning, demonstrating that parent speech and child gesture use are powerful predictors of later vocabulary. However, an additional body of research indicates that these relationships don’t always replicate, particularly when assessed in different populations, contexts, or developmental periods.

The current study examines the relationships between infant gesture, parent speech, and infant vocabulary over the course of the second year (10-22 months of age). Through the use of detailed coding of dyadic mother-child play interactions and a combination of quantitative and qualitative data analytic methods, the process of communicative development was explored. Findings reveal non-linear patterns of growth in both parent speech content and child gesture use. Analyses of contingency in dyadic interactions reveal that children are active contributors to communicative engagement through their use of gestures, shaping the type of input they receive from parents, which in turn influences child vocabulary acquisition. Recommendations for future studies and the use of nuanced methodologies to assess changes in the dynamic system of dyadic communication are discussed.

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DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.

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BACKGROUND: Coronary artery bypass grafting (CABG) is often used to treat patients with significant coronary heart disease (CHD). To date, multiple longitudinal and cross-sectional studies have examined the association between depression and CABG outcomes. Although this relationship is well established, the mechanism underlying this relationship remains unclear. The purpose of this study was twofold. First, we compared three markers of autonomic nervous system (ANS) function in four groups of patients: 1) Patients with coronary heart disease and depression (CHD/Dep), 2) Patients without CHD but with depression (NonCHD/Dep), 3) Patients with CHD but without depression (CHD/NonDep), and 4) Patients without CHD and depression (NonCHD/NonDep). Second, we investigated the impact of depression and autonomic nervous system activity on CABG outcomes. METHODS: Patients were screened to determine whether they met some of the study's inclusion or exclusion criteria. ANS function (i.e., heart rate, heart rate variability, and plasma norepinephrine levels) were measured. Chi-square and one-way analysis of variance were performed to evaluate group differences across demographic, medical variables, and indicators of ANS function. Logistic regression and multiple regression analyses were used to assess impact of depression and autonomic nervous system activity on CABG outcomes. RESULTS: The results of the study provide some support to suggest that depressed patients with CHD have greater ANS dysregulation compared to those with only CHD or depression. Furthermore, independent predictors of in-hospital length of stay and non-routine discharge included having a diagnosis of depression and CHD, elevated heart rate, and low heart rate variability. CONCLUSIONS: The current study presents evidence to support the hypothesis that ANS dysregulation might be one of the underlying mechanisms that links depression to cardiovascular CABG surgery outcomes. Thus, future studies should focus on developing and testing interventions that targets modifying ANS dysregulation, which may lead to improved patient outcomes.

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Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus-challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 beta and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies.

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BACKGROUND: West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease. METHODS: Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis. RESULTS: Statistically different bacterial signatures (P<0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of Veillonella and Streptococcus, with a moderate number of Capnocytophaga. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (Selenomonas, Eubacterium, Dialister). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease. CONCLUSIONS: Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.

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A literature review of howler parasites provides the basis for an overview of the ecological significance of parasite surveys in primates. Within this framework, we have added insights into the interactions between primate hosts and their parasites from a long-term study in Costa Rica. We collected fecal samples from mantled howlers (Alouatta palliata) over a 9-year period (19861994 inclusive) and analyzed them for parasite eggs, larvae, cysts, and oocysts. We found many misperceptions inherent in the typical methodology of primate parasite surveys and in the reporting of the findings. Our work in Costa Rica suggests that a snapshot effect occurs with most surveys. A static view does not reflect the dynamic and changing ecological interaction between host and parasite. We describe some problems with parasite data analyses that emphasize the need for long-term longitudinal surveys in wild primate groups.

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Given the increases in spatial resolution and other improvements in climate modeling capabilities over the last decade since the CMIP3 simulations were completed, CMIP5 provides a unique opportunity to assess scientific understanding of climate variability and change over a range of historical and future conditions. With participation from over 20 modeling groups and more than 40 global models, CMIP5 represents the latest and most ambitious coordinated international climate model intercomparison exercise to date. Observations dating back to 1900 show that the temperatures in the twenty-first century have the largest spatial extent of record breaking and much above normal mean monthly maximum and minimum temperatures. The 20-yr return value of the annual maximum or minimum daily temperature is one measure of changes in rare temperature extremes.

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Using longitudinal data, the present study examined change in midlife neuroticism following trauma exposure. Our primary analyses included 670 participants (M(age) = 60.55; 65.22% male, 99.70% Caucasian) who completed the NEO Personality Inventory at ages 42 and 50 and reported their lifetime exposure to traumatic events approximately 10 years later. No differences in pre- and post-trauma neuroticism scores were found among individuals who experienced all of their lifetime traumas in the interval between the personality assessments. Results were instead consistent with normative age-related declines in neuroticism throughout adulthood. Furthermore, longitudinal changes in neuroticism scores did not differ between individuals with and without histories of midlife trauma exposure. Examination of change in neuroticism following life-threatening traumas yielded a comparable pattern of results. Analysis of facet-level scores largely replicated findings from the domain scores. Overall, our findings suggest that neuroticism does not reliably change following exposure to traumatic events in middle adulthood. Supplemental analyses indicated that individuals exposed to life-threatening traumas in childhood or adolescence reported higher midlife neuroticism than individuals who experienced severe traumas in adulthood. Life-threatening traumatic events encountered early in life may have a more pronounced impact on adulthood personality than recent traumatic events.

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If and only if each single cue uniquely defines its target, a independence model based on fragment theory can predict the strength of a combined dual cue from the strengths of its single cue components. If the single cues do not each uniquely define their target, no single monotonic function can predict the strength of the dual cue from its components; rather, what matters is the number of possible targets. The probability of generating a target word was .19 for rhyme cues, .14 for category cues, and .97 for rhyme-plus-category dual cues. Moreover, some pairs of cues had probabilities of producing their targets of .03 when used individually and 1.00 when used together, whereas other pairs had moderate probabilities individually and together. The results, which are interpreted in terms of multiple constraints limiting the number of responses, show why rhymes, which play a minimal role in laboratory studies of memory, are common in real-world mnemonics.

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Due to changes in cannabis policies, concerns about cannabis use (CU) in adolescents have increased. The population of nonwhite groups is growing quickly in the United States. We examined perceived CU norms and their association with CU and CU disorder (CUD) for White, Black, Hispanic, Native-American, Asian-American, Native Hawaiian/Pacific Islander (NH/PI), and mixed-race adolescents. Data were from adolescents (12-17 years) in the 2004-2012 National Surveys on Drug Use and Health (N = 163,837). Substance use and CUD were assessed by computer-assisted, self-interviewing methods. Blacks, Hispanics, Native-Americans, and mixed-race adolescents had greater odds of past-year CU and CUD than Whites. Among past-year cannabis users (CUs), Hispanics and Native-Americans had greater odds of having a CUD than Whites. Asian-Americans had the highest prevalence of perceived parental or close friends' CU disapproval. Native-Americans and mixed-race adolescents had lower odds than Whites of perceiving CU disapproval from parents or close friends. In adjusted analyses, adolescent's disapproval of CU, as well as perceived disapproval by parents or close friends, were associated with a decreased odds of CU in each racial/ethnic group, except for NHs/PIs. Adolescent's disapproval of CU was associated with a decreased odds of CUD among CUs for Whites (personal, parental, and close friends' disapproval), Hispanics (personal, parental, and close friends' disapproval), and mixed-race adolescents (personal, close friends' disapproval). Racial/ethnic differences in adolescent CU prevalence were somewhat consistent with adolescents' reports of CU norm patterns. Longitudinal research on CU health effects should oversample nonwhite adolescents to assure an adequate sample for analysis and reporting.

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Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.

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Cryptococcus neoformans var. grubii (Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MATa allele were observed in both clinical and environmental isolates; however, the mating-type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MATa and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans.