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1.
Psychol Med ; 53(15): 7329-7340, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37194497

RESUMO

BACKGROUND: Intimate partner violence (IPV) alters women's neurobiological stress response systems. We propose that individual differences early in the attentional processing of threats are associated with these neurobiological mechanisms and contribute to mental illness in this population. METHODS: We assessed attentional bias in relation to threat (AB) in women survivors of IPV (n = 69) and controls (n = 36), and examined overall cortisol secretion using hair cortisol (HC), and stress responsiveness measuring salivary cortisol and α-amylase (sAA) before (T0), and after (T1, T2) an acute psychosocial stress task (Trier Social Stress Test). We used repeated-measures ANCOVAs to explore the associations between Group (IPV, control) and AB with acute stress response, and regression models to examine the associations with mental health symptoms. RESULTS: There were no between-group differences in HC levels. An interaction between Group and AB was found regarding cortisol reactivity (p < 0.05). IPV women with threat avoidance AB showed a blunted cortisol response compared to controls and to IPV participants with threat vigilance AB. The association between sAA reactivity and the interaction between Group, AB, and time approached significance (p = 0.07), with a trend to lower sAA levels particularly in IPV women with threat avoidance AB. Group and cortisol reactivity were associated with symptoms of depression, generalized anxiety, and post-traumatic stress disorder (8-20% explained variance). CONCLUSIONS: Threat avoidance AB is associated with blunted acute cortisol response among women exposed to chronic stress (IPV). Experiencing IPV and acute cortisol response appear to be clearly implicated in long-term mental health problems.


Assuntos
Viés de Atenção , Violência por Parceiro Íntimo , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Hidrocortisona , Violência por Parceiro Íntimo/psicologia , Ansiedade/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia
2.
J Comput Graph Stat ; 29(3): 535-546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38919169

RESUMO

A new empirical Bayes approach to variable selection in the context of generalized linear models is developed. The proposed algorithm scales to situations in which the number of putative explanatory variables is very large, possibly much larger than the number of responses. The coefficients in the linear predictor are modeled as a three-component mixture allowing the explanatory variables to have a random positive effect on the response, a random negative effect, or no effect. A key assumption is that only a small (but unknown) fraction of the candidate variables have a non-zero effect. This assumption, in addition to treating the coefficients as random effects facilitates an approach that is computationally efficient. In particular, the number of parameters that have to be estimated is small, and remains constant regardless of the number of explanatory variables. The model parameters are estimated using a Generalized Alternating Maximization algorithm which is scalable, and leads to significantly faster convergence compared with simulation-based fully Bayesian methods.

3.
Cell Host Microbe ; 25(4): 553-564.e7, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974084

RESUMO

Host genetic variation influences microbiome composition. While studies have focused on associations between the gut microbiome and specific alleles, gene copy number (CN) also varies. We relate microbiome diversity to CN variation of the AMY1 locus, which encodes salivary amylase, facilitating starch digestion. After imputing AMY1-CN for ∼1,000 subjects, we identified taxa differentiating fecal microbiomes of high and low AMY1-CN hosts. In a month-long diet intervention study, we show that diet standardization drove gut microbiome convergence, and AMY1-CN correlated with oral and gut microbiome composition and function. The microbiomes of low-AMY1-CN subjects had enhanced capacity to break down complex carbohydrates. High-AMY1-CN subjects had higher levels of salivary Porphyromonas; their gut microbiota had increased abundance of resistant starch-degrading microbes, produced higher levels of short-chain fatty acids, and drove higher adiposity when transferred to germ-free mice. This study establishes AMY1-CN as a genetic factor associated with microbiome composition and function.


Assuntos
Amilases/genética , Trato Gastrointestinal/microbiologia , Dosagem de Genes , Microbiota , Boca/microbiologia , Saliva/enzimologia , Animais , Vida Livre de Germes , Humanos , Camundongos
4.
Transl Psychiatry ; 6(10): e913, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27727241

RESUMO

Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2). Participants were randomly assigned to three stimulation conditions: direct-current (DC) stimulation, aimed at enhancing extinction-learning; low-frequency alternating-current (AC) stimulation, aimed at interfering with reconsolidation of the activated fear memory; and sham stimulation. The effect of stimulation on these processes was assessed in the subsequent extinction recall phase (Day 3), using skin conductance response and self-reports. Results indicate that AC stimulation potentiated the expression of fear response, whereas DC stimulation led to overgeneralization of fear response to non-reinforced stimuli. The current study demonstrates the capability of electrical stimulation targeting the medial prefrontal cortex to modulate fear extinction processes. However, the stimulation parameters tested here yielded effects opposite to those anticipated and could be clinically detrimental. These results highlight the potential capacity of stimulation to manipulate processes relevant for treatment of anxiety and stress-related disorders, but also emphasize the need for additional research to identify delivery parameters to enable its translation into clinical practice. Clinical trial identifiers: Modulation of Fear Extinction Processes Using Transcranial Electrical Stimulation; https://clinicaltrials.gov/show/NCT02723188; NCT02723188 NCT02723188.


Assuntos
Extinção Psicológica/fisiologia , Medo/fisiologia , Medo/psicologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Transcraniana por Corrente Contínua , Adulto , Condicionamento Clássico/fisiologia , Feminino , Resposta Galvânica da Pele/fisiologia , Generalização Psicológica/fisiologia , Humanos , Masculino , Adulto Jovem
5.
Psychol Med ; 46(12): 2627-36, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27377418

RESUMO

BACKGROUND: Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat. METHOD: We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments. RESULTS: PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01-9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches. CONCLUSIONS: Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.


Assuntos
Viés de Atenção/fisiologia , Distúrbios de Guerra/prevenção & controle , Militares/psicologia , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Adolescente , Adulto , Método Duplo-Cego , Seguimentos , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
6.
Transl Psychiatry ; 6: e801, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27138800

RESUMO

Trauma causes variable risk of posttraumatic stress symptoms (PTSS) owing to yet-unknown genome-neuronal interactions. Here, we report co-intensified amygdala and ventromedial prefrontal cortex (vmPFC) emotional responses that may overcome PTSS in individuals with the single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene. We have recently shown that in individuals with the minor rs17228616 allele, this SNP interrupts AChE suppression by microRNA (miRNA)-608, leading to cortical elevation of brain AChE and reduced cortisol and the miRNA-608 target GABAergic modulator CDC42, all stress-associated. To examine whether this SNP has effects on PTSS and threat-related brain circuits, we exposed 76 healthy Israel Defense Forces soldiers who experienced chronic military stress to a functional magnetic resonance imaging task of emotional and neutral visual stimuli. Minor allele individuals predictably reacted to emotional stimuli by hyperactivated amygdala, a hallmark of PTSS and a predisposing factor of posttraumatic stress disorder (PTSD). Despite this, minor allele individuals showed no difference in PTSS levels. Mediation analyses indicated that the potentiated amygdala reactivity in minor allele soldiers promoted enhanced vmPFC recruitment that was associated with their limited PTSS. Furthermore, we found interrelated expression levels of several miRNA-608 targets including CD44, CDC42 and interleukin 6 in human amygdala samples (N=7). Our findings suggest that miRNA-608/AChE interaction is involved in the threat circuitry and PTSS and support a model where greater vmPFC regulatory activity compensates for amygdala hyperactivation in minor allele individuals to neutralize their PTSS susceptibility.


Assuntos
Acetilcolinesterase/genética , MicroRNAs/genética , Córtex Pré-Frontal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Israel , Imageamento por Ressonância Magnética/métodos , Masculino , Militares , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
7.
Psychol Med ; 45(5): 1011-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25192244

RESUMO

BACKGROUND: Military training is a chronic stressful period that often induces stress-related psychopathology. Stress vulnerability and resilience depend on personality trait anxiety, attentional threat bias and prefrontal-limbic dysfunction. However, how these neurobehavioral elements interact with regard to the development of symptoms following stress remains unclear. METHOD: Fifty-five healthy combat soldiers undergoing intensive military training completed functional magnetic resonance imaging (fMRI) testing while performing the dot-probe task (DPT) composed of angry (threat) and neutral faces. Participants were then stratified according to their bias tendency to avoidance (n = 25) or vigilance (n = 30) groups, categorized as high or low trait anxiety and assessed for post-stress symptom severity. RESULTS: Avoidance compared to vigilance tendency was associated with fewer post-trauma symptoms and increased hippocampal response to threat among high anxious but not low anxious individuals. Importantly, mediation analysis revealed that only among high anxious individuals did hippocampal activity lead to lower levels of symptoms through avoidance bias tendency. However, in the whole group, avoidance bias was modulated by the interplay between the hippocampus and the dorsal anterior cingulate cortex (dACC). CONCLUSIONS: Our results provide a neurobehavioral model to explain the resilience to post-trauma symptoms following chronic exposure. The model points to the importance of considering threat bias tendency in addition to personality traits when investigating the brain response and symptoms of trauma. Such a multi-parametric approach that accounts for individual behavioral sensitivities may also improve brain-driven treatments of anxiety, possibly by targeting the interplay between the hippocampus and the dACC.


Assuntos
Giro do Cíngulo/fisiopatologia , Hipocampo/fisiopatologia , Militares/psicologia , Personalidade , Resiliência Psicológica , Transtornos de Estresse Traumático/fisiopatologia , Estresse Psicológico/fisiopatologia , Adolescente , Ansiedade/fisiopatologia , Nível de Alerta , Encéfalo/fisiopatologia , Medo , Neuroimagem Funcional , Humanos , Individualidade , Imageamento por Ressonância Magnética , Masculino , Transtornos de Estresse Traumático/psicologia , Estresse Psicológico/psicologia , Adulto Jovem
8.
Reprod Sci ; 22(6): 685-95, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25367051

RESUMO

Vitamin D is linked to a number of adverse pregnancy outcomes through largely unknown mechanisms. This study was conducted to examine the role of vitamin D status in metabolomic profiles in a group of 30 pregnant, African American adolescents (17.1 ± 1.1 years) at midgestation (26.8 ± 2.8 weeks), in 15 adolescents with 25-hydroxy vitamin D (25(OH)D) ≥20 ng/mL, and in 15 teens with 25(OH)D <20 ng/mL. Serum metabolomic profiles were examined using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. A novel hierarchical mixture model was used to evaluate differences in metabolite profiles between low and high groups. A total of 326 compounds were identified and included in subsequent statistical analyses. Eleven metabolites had significantly different means between the 2 vitamin D groups, after correcting for multiple hypothesis testing: pyridoxate, bilirubin, xylose, and cholate were higher, and leukotrienes, 1,2-propanediol, azelate, undecanedioate, sebacate, inflammation associated complement component 3 peptide (HWESASXX), and piperine were lower in serum from adolescents with 25(OH)D ≥20 ng/mL. Lower maternal vitamin D status at midgestation impacted serum metabolic profiles in pregnant adolescents.


Assuntos
Metabolômica , Gravidez na Adolescência/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adolescente , Negro ou Afro-Americano , Fatores Etários , Biomarcadores/sangue , Cromatografia Líquida , Análise por Conglomerados , Metabolismo Energético , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Idade Gestacional , Humanos , Intestinos/microbiologia , Metabolômica/métodos , Microbiota , New York/epidemiologia , Gravidez , Gravidez na Adolescência/etnologia , Prevalência , Espectrometria de Massas em Tandem , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/etnologia
9.
PLoS One ; 9(5): e97137, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24817125

RESUMO

Intermediate (VISA-type) vancomycin resistance in Staphylococcus aureus has been associated with a range of physiologic and genetic alterations. Previous work described the emergence of VISA-type resistance in two clonally-distinct series of isolates. In both series (the first belonging to MRSA clone ST8-USA300, and the second to ST5-USA100), resistance was conferred by a single mutation in yvqF (a negative regulator of the vraSR two-component system associated with vancomycin resistance). In the USA300 series, resistance was reversed by a secondary mutation in vraSR. In this study, we combined systems-level metabolomic profiling with statistical modeling techniques to discover specific, reversible metabolic alterations associated with the VISA phenotype.


Assuntos
Proteínas de Bactérias/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Resistência a Vancomicina/genética , Proteínas de Bactérias/genética , Cromatografia Líquida , Proteínas de Ligação a DNA/metabolismo , Espectrometria de Massas , Metabolômica/métodos , Modelos Estatísticos , Análise de Componente Principal , Especificidade da Espécie
10.
Psychol Med ; 44(10): 2077-84, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24131552

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is a chronic and difficult to treat psychiatric disorder. Objective, performance-based diagnostic markers that uniquely index risk for PTSD above and beyond subjective self-report markers could inform attempts to improve prevention and early intervention. We evaluated the predictive value of threat-related attention bias measured immediately after a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up. We measured the predictive contribution of attentional threat bias above and beyond that of the more established marker of risk for PTSD, self-reported psychological dissociation. METHOD: Dissociation symptoms and threat-related attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean age = 35.02 years, 356 males) within 24 h of admission to an emergency department (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow-up using the Clinician-Administered PTSD Scale (CAPS). RESULTS: Self-reported dissociation symptoms significantly accounted for 16% of the variance in PTSD at follow-up, and attention bias toward threat significantly accounted for an additional 4% of the variance in PTSD. CONCLUSIONS: Threat-related attention bias can be reliably measured in the context of a hospital ED and significantly predicts risk for later PTSD. Possible mechanisms underlying the association between threat bias following a potentially traumatic event and risk for PTSD are discussed. The potential application of an attention bias modification treatment (ABMT) tailored to reduce risk for PTSD is suggested.


Assuntos
Acidentes de Trânsito/psicologia , Ansiedade/diagnóstico , Atenção/fisiologia , Transtornos Dissociativos/diagnóstico , Medo/fisiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Sobreviventes/psicologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
11.
J Behav Ther Exp Psychiatry ; 44(3): 285-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23391516

RESUMO

BACKGROUND AND OBJECTIVES: Previous research suggests that attention bias toward threat contributes to the development and maintenance of anxiety. The current study extends this work by mapping the neural correlates of experimentally-induced changes in attention bias. The study examines both behavioral and psychophysiological changes associated with experimentally-induced changes in threat bias. METHODS: Thirty-four non-anxious female adults were randomly assigned to one of two conditions: training attention toward threat or placebo control. Attention bias was assessed and trained via a modified dot-probe task. Participants completed pre- and post-training assessments of attention bias and stress reactivity. As well, EEG was collected during pre- and post-test assessment of attention bias using the dot-probe task. RESULTS: Training induced significant changes in attention bias, though findings were complicated by group differences in baseline threat-bias scores. Compared to controls, those in the training group showed greater depression vulnerability to a post-training stressor and increased P2 amplitude, an ERP component associated with attention toward threat, during the dot-probe task. LIMITATIONS: Although participants were randomly assigned to groups, there were still group differences in pre-training bias scores. Also, while the use of a stress task before the initial assessment of attention bias was used to control for initial differences in stress vulnerability, this may have altered pre-bias scores since participants completed this task immediately after being stressed. CONCLUSIONS: These findings demonstrate training-induced changes in behavior and neural response patterns relevant to work on attention bias modification.


Assuntos
Atenção/fisiologia , Potenciais Evocados Visuais/fisiologia , Estresse Psicológico/psicologia , Adulto , Afeto/fisiologia , Ansiedade , Terapia Cognitivo-Comportamental/métodos , Expressão Facial , Feminino , Humanos , Estimulação Luminosa , Tempo de Reação/fisiologia , Estresse Psicológico/fisiopatologia
12.
FASEB J ; 27(3): 1245-53, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23195033

RESUMO

This study investigated the influence of maternal choline intake on the human placental transcriptome, with a special interest in its role in modulating placental vascular function. Healthy pregnant women (n=26, wk 26-29 gestation) were randomized to 480 mg choline/d, an intake level approximating the adequate intake of 450 mg/d, or 930 mg/d for 12 wk. Maternal blood and placental samples were retrieved at delivery. Whole genome expression microarrays were used to identify placental genes and biological processes impacted by maternal choline intake. Maternal choline intake influenced a wide array of genes (n=166) and biological processes (n=197), including those related to vascular function. Of special interest was the 30% down-regulation (P=0.05) of the antiangiogenic factor and preeclampsia risk marker fms-like tyrosine kinase-1 (sFLT1) in the placenta tissues obtained from the 930 vs. 480 mg/d choline intake group. Similar decreases (P=0.04) were detected in maternal blood sFLT1 protein concentrations. The down-regulation of sFLT1 by choline treatment was confirmed in a human trophoblast cell culture model and may be related to enhanced acetylcholine signaling. These findings indicate that supplementing the maternal diet with extra choline may improve placental angiogenesis and mitigate some of the pathological antecedents of preeclampsia.


Assuntos
Inibidores da Angiogênese/sangue , Colina/administração & dosagem , Suplementos Nutricionais , Neovascularização Fisiológica/fisiologia , Terceiro Trimestre da Gravidez/sangue , Gravidez/sangue , Trofoblastos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Acetilcolina/sangue , Adulto , Biomarcadores/sangue , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Pré-Eclâmpsia/sangue , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Nascimento a Termo/sangue , Transcriptoma/efeitos dos fármacos , Transcriptoma/fisiologia , Trofoblastos/citologia
13.
PLoS One ; 7(11): e46736, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23133592

RESUMO

BACKGROUND: Pregnancy induces physiological adaptations that may involve, or contribute to, alterations in the genomic landscape. Pregnancy also increases the nutritional demand for choline, an essential nutrient that can modulate epigenomic and transcriptomic readouts secondary to its role as a methyl donor. Nevertheless, the interplay between human pregnancy, choline and the human genome is largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: As part of a controlled feeding study, we assessed the influence of pregnancy and choline intake on maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26-29 gestation) and nonpregnant (n = 21) women were randomized to choline intakes of 480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks. Blood leukocytes were acquired at study week 0 and study week 12 for microarray, DNA damage and global DNA/histone methylation measurements. A main effect of pregnancy that was independent of choline intake was detected on several of the maternal leukocyte genomic markers. Compared to nonpregnant women, third trimester pregnant women exhibited higher (P<0.05) transcript abundance of defense response genes associated with the innate immune system including pattern recognition molecules, neutrophil granule proteins and oxidases, complement proteins, cytokines and chemokines. Pregnant women also exhibited higher (P<0.001) levels of DNA damage in blood leukocytes, a genomic marker of oxidative stress. No effect of choline intake was detected on the maternal leukocyte genomic markers with the exception of histone 3 lysine 4 di-methylation which was lower among pregnant women in the 930 versus 480 mg/d choline intake group. CONCLUSIONS: Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.


Assuntos
Dano ao DNA , Imunidade Inata , Ativação Transcricional , Adulto , Estudos de Casos e Controles , Colina/metabolismo , Análise por Conglomerados , Dieta , Epigenômica , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma Humano , Genômica , Histonas/metabolismo , Humanos , Interleucina-6/biossíntese , Leucócitos/metabolismo , Leucócitos Mononucleares/citologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Estresse Oxidativo , Gravidez , Terceiro Trimestre da Gravidez , Fator de Necrose Tumoral alfa/biossíntese
14.
Stat Med ; 31(27): 3347-65, 2012 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-22733577

RESUMO

When event data are retrospectively reported, more temporally distal events tend to get 'heaped' on even multiples of reporting units. Heaping may introduce a type of attenuation bias because it causes researchers to mismatch time-varying right-hand side variables. We develop a model-based approach to estimate the extent of heaping in the data and how it affects regression parameter estimates. We use smoking cessation data as a motivating example, but our method is general. It facilitates the use of retrospective data from the multitude of cross-sectional and longitudinal studies worldwide that collect and potentially could collect event data.


Assuntos
Algoritmos , Interpretação Estatística de Dados , Modelos Estatísticos , Estudos Retrospectivos , Processos Estocásticos , Simulação por Computador , Humanos , Método de Monte Carlo , Abandono do Hábito de Fumar/métodos
15.
Stat Appl Genet Mol Biol ; 11(1): Article 8, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22499680

RESUMO

Testing for unequal variances is usually performed in order to check the validity of the assumptions that underlie standard tests for differences between means (the t-test and anova). However, existing methods for testing for unequal variances (Levene's test and Bartlett's test) are notoriously non-robust to normality assumptions, especially for small sample sizes. Moreover, although these methods were designed to deal with one hypothesis at a time, modern applications (such as to microarrays and fMRI experiments) often involve parallel testing over a large number of levels (genes or voxels). Moreover, in these settings a shift in variance may be biologically relevant, perhaps even more so than a change in the mean. This paper proposes a parsimonious model for parallel testing of the equal variance hypothesis. It is designed to work well when the number of tests is large; typically much larger than the sample sizes. The tests are implemented using an empirical Bayes estimation procedure which `borrows information' across levels. The method is shown to be quite robust to deviations from normality, and to substantially increase the power to detect differences in variance over the more traditional approaches even when the normality assumption is valid.


Assuntos
Modelos Estatísticos , Análise de Variância , Teorema de Bayes , Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Tamanho da Amostra
16.
PLoS One ; 7(2): e30827, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22319591

RESUMO

Shewanella oneidensis is a target of extensive research in the fields of bioelectrochemical systems and bioremediation because of its versatile metabolic capabilities, especially with regard to respiration with extracellular electron acceptors. The physiological activity of S. oneidensis to respire at electrodes is of great interest, but the growth conditions in thin-layer biofilms make physiological analyses experimentally challenging. Here, we took a global approach to evaluate physiological activity with an electrode as terminal electron acceptor for the generation of electric current. We performed expression analysis with DNA microarrays to compare the overall gene expression with an electrode to that with soluble iron(III) or oxygen as the electron acceptor and applied new hierarchical model-based statistics for the differential expression analysis. We confirmed the differential expression of many genes that have previously been reported to be involved in electrode respiration, such as the entire mtr operon. We also formulate hypotheses on other possible gene involvements in electrode respiration, for example, a role of ScyA in inter-protein electron transfer and a regulatory role of the cbb3-type cytochrome c oxidase under anaerobic conditions. Further, we hypothesize that electrode respiration imposes a significant stress on S. oneidensis, resulting in higher energetic costs for electrode respiration than for soluble iron(III) respiration, which fosters a higher metabolic turnover to cover energy needs. Our hypotheses now require experimental verification, but this expression analysis provides a fundamental platform for further studies into the molecular mechanisms of S. oneidensis electron transfer and the physiologically special situation of growth on a poised-potential surface.


Assuntos
Transporte de Elétrons , Regulação Bacteriana da Expressão Gênica , Shewanella/genética , Transcrição Gênica , Eletrodos , Compostos Férricos/metabolismo , Perfilação da Expressão Gênica , Oxigênio/metabolismo , Shewanella/metabolismo
17.
J Exp Biol ; 214(Pt 17): 2864-70, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21832129

RESUMO

The role of sound in Drosophila melanogaster courtship, along with its perception via the antennae, is well established, as is the ability of this fly to learn in classical conditioning protocols. Here, we demonstrate that a neutral acoustic stimulus paired with a sucrose reward can be used to condition the proboscis-extension reflex, part of normal feeding behavior. This appetitive conditioning produces results comparable to those obtained with chemical stimuli in aversive conditioning protocols. We applied a logistic model with general estimating equations to predict the dynamics of learning, which successfully predicts the outcome of training and provides a quantitative estimate of the rate of learning. Use of acoustic stimuli with appetitive conditioning provides both an alternative to models most commonly used in studies of learning and memory in Drosophila and a means of testing hearing in both sexes, independently of courtship responsiveness.


Assuntos
Estimulação Acústica , Condicionamento Clássico , Drosophila melanogaster/fisiologia , Comportamento Alimentar , Estimulação Acústica/métodos , Animais , Comportamento Apetitivo , Feminino , Masculino , Modelos Biológicos
18.
Depress Anxiety ; 28(5): 406-11, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21381159

RESUMO

BACKGROUND: Recent studies find a correlation between attentional threat avoidance under stress and posttraumatic stress symptoms. In this study, we assessed this association longitudinally in exposed and unexposed individuals. The degree of threat avoidance during exposure was expected to predict levels of posttraumatic stress symptoms 1 year later. METHODS: Thirty-two participants were recruited and followed for 12 months, including 18 subjects exposed to rocket attacks and 14 nonexposed subjects. At 1-year follow-up, participants completed self-reports and an attention dot-probe task assessing threat-related bias. RESULTS: State anxiety decreased at follow-up in exposed participants, though posttraumatic stress disorder (PTSD) and depression symptoms remained higher in exposed than in the nonexposed group. Attentional threat avoidance during imminent danger in the exposed group changed to threat attendance a year later, such that both the exposed and the nonexposed group exhibited similar threat bias patterns. As hypothesized, in the exposed group, stronger attentional threat avoidance during stress exposure predicted higher levels of PTSD symptoms 1 year later. CONCLUSIONS: Attention bias away from threat during acute stress may relate to risk for PTSD. This suggests that neurocognitive measures may index risk for PTSD.


Assuntos
Nível de Alerta , Atenção , Aprendizagem da Esquiva , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Guerra , Adolescente , Adulto , Lista de Checagem , Feminino , Seguimentos , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Oriente Médio , Orientação , Reconhecimento Visual de Modelos , Tempo de Reação , Fatores de Risco , Semântica , Adulto Jovem
19.
Bioresour Technol ; 102(3): 2623-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21036604

RESUMO

Bioelectrochemical systems (BESs) employing mixed microbial communities as biocatalysts are gaining importance as potential renewable energy, bioremediation, or biosensing devices. While we are beginning to understand how individual microbial species interact with an electrode as electron donor, little is known about the interactions between different microbial species in a community: sugar fermenting bacteria can interact with current producing microbes in a fashion that is either neutral, positively enhancing, or even negatively affecting. Here, we compare the bioelectrochemical performance of Shewanella oneidensis in a pure-culture and in a co-culture with the homolactic acid fermenter Lactococcus lactis at conditions that are pertinent to conventional BES operation. While S. oneidensis alone can only use lactate as electron donor for current production, the co-culture is able to convert glucose into current with a comparable coulombic efficiency of ∼17%. With (electro)-chemical analysis and transcription profiling, we found that the BES performance and S. oneidensis physiology were not significantly different whether grown as a pure- or co-culture. Thus, the microbes worked together in a purely substrate based (neutral) relationship. These co-culture experiments represent an important step in understanding microbial interactions in BES communities with the goal to design complex microbial communities, which specifically convert target substrates into electricity.


Assuntos
Fontes de Energia Bioelétrica , Reatores Biológicos/microbiologia , Eletrodos/microbiologia , Glucose/metabolismo , Ácido Láctico/metabolismo , Lactococcus lactis/fisiologia , Shewanella/fisiologia , Técnicas de Cocultura/instrumentação , Transporte de Elétrons , Desenho de Equipamento , Análise de Falha de Equipamento
20.
Psychol Med ; 41(4): 699-707, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21108868

RESUMO

BACKGROUND: Acute stress disorder involves prominent symptoms of threat avoidance. Preliminary cross-sectional data suggest that such threat-avoidance symptoms may also manifest cognitively, as attentional threat avoidance. Confirming these findings in a longitudinal study might provide insights on risk prediction and anxiety prevention in traumatic exposures. METHOD: Attention-threat bias and post-traumatic symptoms were assessed in soldiers at two points in time: early in basic training and 23 weeks later, during advanced combat training. Based on random assignment, the timing of the repeat assessment occurred in one of two schedules: for a combat simulation group, the repeat assessment occurred immediately following a battlefield simulation exercise, and for a control group, the assessment occurred shortly before this exercise. RESULTS: Both groups showed no threat-related attention bias at initial assessments. Following acute stress, the combat simulation group exhibited a shift in attention away from threat whereas the control group showed no change in attention bias. Stronger threat avoidance in the combat simulation group correlated with severity of post-traumatic symptoms. Such an association was not found in the control group. CONCLUSIONS: Acute stress may lead some individuals to shift their attention away from threats, perhaps to minimize stress exposure. This acute attention response may come at a psychological cost, given that it correlates with post-traumatic stress disorder (PTSD) symptoms. Further research is needed to determine how these associations relate to full-blown PTSD in soldier and civilian populations.


Assuntos
Nível de Alerta , Atenção , Distúrbios de Guerra/diagnóstico , Distúrbios de Guerra/prevenção & controle , Sinais (Psicologia) , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/prevenção & controle , Transtornos de Ansiedade/psicologia , Percepção de Cores , Distúrbios de Guerra/psicologia , Mecanismos de Defesa , Seguimentos , Humanos , Masculino , Orientação , Aprendizagem por Associação de Pares , Reconhecimento Visual de Modelos , Tempo de Reação , Semântica , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto Jovem
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