PARENTAL CHILDHOOD ADVERSITY, DEPRESSIVE SYMPTOMS, AND PARENTING QUALITY: EFFECTS ON TODDLER SELF-REGULATION IN CHILD WELFARE SERVICES INVOLVED FAMILIES.

PubMed

Spieker, Susan J; Oxford, Monica L; Fleming, Charles B; Lohr, Mary Jane

2018-01-01

Parents who are involved with child welfare services (CWSI) often have a history of childhood adversity and depressive symptoms. Both affect parenting quality, which in turn influences child adaptive functioning. We tested a model of the relations between parental depression and child regulatory outcomes first proposed by K. Lyons-Ruth, R. Wolfe, A. Lyubchik, and R. Steingard (2002). We hypothesized that both parental depression and parenting quality mediate the effects of parental early adversity on offspring regulatory outcomes. Participants were 123 CWSI parents and their toddlers assessed three times over a period of 6 months. At Time 1, parents reported on their childhood adversity and current depressive symptoms. At Time 2, parents' sensitivity to their child's distress and nondistress cues was rated from a videotaped teaching task. At Time 3, observers rated children's emotional regulation, orientation/engagement, and secure base behavior. The results of a path model partly supported the hypotheses. Parent childhood adversity was associated with current depressive symptoms, which in turn related to parent sensitivity to child distress, but not nondistress. Sensitivity to distress also predicted secure base behavior. Depression directly predicted orientation/engagement, also predicted by sensitivity to nondistress. Sensitivity to distress predicted emotion regulation and orientation/engagement. Results are discussed in terms of intervention approaches for CWSI families. © 2017 Michigan Association for Infant Mental Health.

Preoperative Falls Predict Postoperative Falls, Functional Decline, and Surgical Complications.

PubMed

Kronzer, Vanessa L; Jerry, Michelle R; Ben Abdallah, Arbi; Wildes, Troy S; Stark, Susan L; McKinnon, Sherry L; Helsten, Daniel L; Sharma, Anshuman; Avidan, Michael S

2016-10-01

Falls are common and linked to morbidity. Our objectives were to characterize postoperative falls, and determine whether preoperative falls independently predicted postoperative falls (primary outcome), functional dependence, quality of life, complications, and readmission. This prospective cohort study included 7982 unselected patients undergoing elective surgery. Data were collected from the medical record, a baseline survey, and follow-up surveys approximately 30days and one year after surgery. Fall rates (per 100 person-years) peaked at 175 (hospitalization), declined to 140 (30-day survey), and then to 97 (one-year survey). After controlling for confounders, a history of one, two, and ≥three preoperative falls predicted postoperative falls at 30days (adjusted odds ratios [aOR] 2.3, 3.6, 5.5) and one year (aOR 2.3, 3.4, 6.9). One, two, and ≥three falls predicted functional decline at 30days (aOR 1.2, 2.4, 2.4) and one year (aOR 1.3, 1.5, 3.2), along with in-hospital complications (aOR 1.2, 1.3, 2.0). Fall history predicted adverse outcomes better than commonly-used metrics, but did not predict quality of life deterioration or readmission. Falls are common after surgery, and preoperative falls herald postoperative falls and other adverse outcomes. A history of preoperative falls should be routinely ascertained. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able to help support early SAR to accelerate drug discovery and decrease late stage attrition in drug discovery projects. In addition, models such as the ones presented here can be used for compound profiling in all development stages.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Added Value of Physical Performance Measures in Predicting Adverse Health-Related Events: Results from the Health, Aging, and Body Composition Study

PubMed Central

Cesari, Matteo; Kritchevsky, Stephen B; Newman, Anne B; Simonsick, Eleanor M; Harris, Tamara B; Penninx, Brenda W; Brach, Jennifer S; Tylavsky, Frances A; Satterfield, Suzanne; Bauer, Doug C; Rubin, Susan M; Visser, Marjolein; Pahor, Marco

2009-01-01

Objectives To determine how three different physical performance measures (PPM) combine for added utility in predicting adverse health events in elders. Design Prospective cohort study. Setting Health, Aging, and Body Composition Study. Participants 3,024 well-functioning older persons (mean age 73.6 years). Measurements Timed gait, repeated chair stands and balance (semi- and full-tandem, and single leg stands each held for 30 seconds) tests were administered at baseline. Usual gait speed was categorized to distinguish high and low risk participants using the previously established 1 m/sec cut-point. The same population-percentile (21.3%) was used to identify cut-points for repeated chair stands (17.05 sec) and balance (53 sec) tests. Cox proportional hazard analyses were performed to evaluate the added value of PPM in predicting mortality, hospitalization, and (severe) mobility limitation events over 6.9 years of follow-up. Results Risk estimates for developing adverse health-related events were similarly large for each of the three high risk groups considered separately. A greater number of PPM scores at the high risk level was associated with a greater risk of developing adverse health-related events. When all three PPMs were considered, having only one poor performance was sufficient to indicate a highly significant higher risk of (severe) lower extremity and mortality events. Conclusion Although gait speed is considered the most important predictor of adverse health events, these findings demonstrate that poor performance on other tests of lower extremity function are equally prognostic. This suggests that chair stand and standing balance performance may be adequate substitutes when gait speed is unavailable. PMID:19207142

External-environmental and internal-health early life predictors of adolescent development.

PubMed

Hartman, Sarah; Li, Zhi; Nettle, Daniel; Belsky, Jay

2017-12-01

A wealth of evidence documents associations between various aspects of the rearing environment and later development. Two evolutionary-inspired models advance explanations for why and how such early experiences shape later functioning: (a) the external-prediction model, which highlights the role of the early environment (e.g., parenting) in regulating children's development, and (b) the internal-prediction model, which emphasizes internal state (i.e., health) as the critical regulator. Thus, by using data from the NICHD Study of Early Child Care and Youth Development, the current project draws from both models by investigating whether the effect of the early environment on later adolescent functioning is subject to an indirect effect by internal-health variables. Results showed a significant indirect effect of internal health on the relation between the early environment and adolescent behavior. Specifically, early environmental adversity during the first 5 years of life predicted lower quality health during childhood, which then led to problematic adolescent functioning and earlier age of menarche for girls. In addition, for girls, early adversity predicted lower quality health that forecasted earlier age of menarche leading to increased adolescent risk taking. The discussion highlights the importance of integrating both internal and external models to further understand the developmental processes that effect adolescent behavior.

Classification and prediction of pilot weather encounters: A discriminant function analysis.

PubMed

O'Hare, David; Hunter, David R; Martinussen, Monica; Wiggins, Mark

2011-05-01

Flight into adverse weather continues to be a significant hazard for General Aviation (GA) pilots. Weather-related crashes have a significantly higher fatality rate than other GA crashes. Previous research has identified lack of situational awareness, risk perception, and risk tolerance as possible explanations for why pilots would continue into adverse weather. However, very little is known about the nature of these encounters or the differences between pilots who avoid adverse weather and those who do not. Visitors to a web site described an experience with adverse weather and completed a range of measures of personal characteristics. The resulting data from 364 pilots were carefully screened and subject to a discriminant function analysis. Two significant functions were found. The first, accounting for 69% of the variance, reflected measures of risk awareness and pilot judgment while the second differentiated pilots in terms of their experience levels. The variables measured in this study enabled us to correctly discriminate between the three groups of pilots considerably better (53% correct classifications) than would have been possible by chance (33% correct classifications). The implications of these findings for targeting safety interventions are discussed.

Early life stress, MAOA, and gene-environment interactions predict behavioral disinhibition in children.

PubMed

Enoch, M-A; Steer, C D; Newman, T K; Gibson, N; Goldman, D

2010-02-01

Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth-3 years) stressors to influence behavior in prepubertal children. The Avon Longitudinal Study of Parents and Children, UK, is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years. In both sexes, exposure to family adversity and stressful life events in the first 3 years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3.5 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1.5 and 2.5 years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity. In a general population sample of prepubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR- stressful life event interactions specifically predicted hyperactivity.

Anxiety Disorders in Adolescents and Psychosocial Outcomes at Age 30

PubMed Central

Essau, Cecilia A.; Lewinsohn, Peter M.; Olaya, Beatriz; Seeley, John R.

2014-01-01

Background Anxiety disorders are associated with adverse psychosocial functioning, and are predictive of a wide range of psychiatric disorders in adulthood. Objective The present study examined the associations between anxiety disorders during childhood and adolescence and psychosocial outcomes at age 30, and sought to address the extent to which psychopathology after age 19 mediated these relations. Method Eight hundred and sixteen participants from a large community sample were interviewed twice during adolescence, at age 24, and at age 30. They completed self-report measures of psychosocial functioning and semi-structured diagnostic interviews during adolescence and young adulthood. Results Childhood anxiety only predicted less years of completed education at age 30, whereas adolescent anxiety predicted income, unemployment, maladjustment, poor coping skills, more chronic stress and life events. Adult major depressive disorder (MDD) was the only disorder predicted by childhood anxiety, whereas adolescent anxiety predicted MDD, substance (SUD) and alcohol abuse/dependence (AUD) in adulthood. No adult psychopathology mediated the relationship between childhood anxiety disorders and psychosocial outcomes at age 30. Adult MDD, SUD and AUD partially or completely mediated the association between adolescent anxiety and most domains of psychosocial functioning at age 30. Limitations The participants are ethically and geographically homogenous, and changes in the diagnostic criteria and the interview schedules across the assessment periods. Conclusion Adolescent anxiety, compared to childhood anxiety, is associated with more adverse psychosocial outcomes at age 30. Adolescent anxiety affects negative outcomes at age 30 directly and through MDD, SUD and AUD. PMID:24456837

Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

PubMed

Raposa, Elizabeth B; Hammen, Constance L; Brennan, Patricia A

2015-01-01

Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

Close Friends’ Psychopathology as a Pathway from Early Adversity to Young Adulthood Depressive Symptoms

PubMed Central

Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia

2014-01-01

Objective Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults’ close friends’ psychological symptoms, and the impact of these close friendships on later depressive symptoms. Method A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants’ mothers provided contemporaneous information about adversity exposure prior to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20’s. Youth also nominated a best friend to complete questionnaires about their own psychopathology at age 20. Results Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends’ psychopathology predicted target youth depressive symptoms two to five years later. Conclusions Results indicate that early adversity continues to affect social functioning throughout young adulthood, and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity. PMID:24871609

Application of gene expression programming and neural networks to predict adverse events of radical hysterectomy in cervical cancer patients.

PubMed

Kusy, Maciej; Obrzut, Bogdan; Kluska, Jacek

2013-12-01

The aim of this article was to compare gene expression programming (GEP) method with three types of neural networks in the prediction of adverse events of radical hysterectomy in cervical cancer patients. One-hundred and seven patients treated by radical hysterectomy were analyzed. Each record representing a single patient consisted of 10 parameters. The occurrence and lack of perioperative complications imposed a two-class classification problem. In the simulations, GEP algorithm was compared to a multilayer perceptron (MLP), a radial basis function network neural, and a probabilistic neural network. The generalization ability of the models was assessed on the basis of their accuracy, the sensitivity, the specificity, and the area under the receiver operating characteristic curve (AUROC). The GEP classifier provided best results in the prediction of the adverse events with the accuracy of 71.96 %. Comparable but slightly worse outcomes were obtained using MLP, i.e., 71.87 %. For each of measured indices: accuracy, sensitivity, specificity, and the AUROC, the standard deviation was the smallest for the models generated by GEP classifier.

Do adverse childhood experiences predict adult interpersonal difficulties? The role of emotion dysregulation.

PubMed

Poole, Julia C; Dobson, Keith S; Pusch, Dennis

2018-06-01

Adverse childhood experiences (ACEs) are risk factors for interpersonal difficulties in adulthood, however the mechanism that underlies this association is unknown. The current study investigated the association of a wide range of ACEs with interpersonal difficulties in adulthood, and tested whether emotion dysregulation mediated the relationship between ACEs and interpersonal difficulties. Patients over the age of 18 were recruited from primary care clinics (N = 4006). Participants completed self-report questionnaires that assessed ACEs, emotion dysregulation, and interpersonal difficulties. Results indicated that, after controlling for a range of demographic variables, each type of ACE significantly predicted increased interpersonal difficulties and that cumulative ACEs predicted increased interpersonal difficulties, F(8, 3137) = 39.68, p < .001, R 2  = 0.09. Further, emotion dysregulation mediated the association between ACEs and interpersonal difficulties, B = 0.79, SE = 0.09, 95% CI [0.64, 0.97]. These findings emphasize the role of childhood adversity on interpersonal functioning in adulthood, and highlight emotion dysregulation as a mechanism by which this association occurs. Results have the potential to inform preventative and treatment efforts to improve adaptive outcomes among individuals with a history of childhood adversity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

PubMed

Gard, Arianna M; Waller, Rebecca; Shaw, Daniel S; Forbes, Erika E; Hariri, Ahmad R; Hyde, Luke W

2017-10-01

Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1 . These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

Differential relationships between social adversity and depressive symptoms by HIV-status and racial/ethnic identity

PubMed Central

Williamson, Timothy J.; Mahmood, Zanjbeel; Kuhn, Taylor P.; Thames, April D.

2016-01-01

Objective Historically marginalized groups are likely to be exposed to social adversity, which predicts important mental health outcomes (e.g., depression). Despite the well-established relationship between adversity and poor health, few studies have examined how adversity differentially predicts mental health among people living with multiple, co-occurring marginalized identities or statuses. The current study fills this gap by examining whether relationships between social adversity and depressive symptoms differed between those living with or without a stigmatized disease (i.e., HIV) and/or marginalized racial/ethnic identity (i.e., African American). Method A community sample of men and women (n = 149) completed questionnaires assessing demographics and depressive symptoms. Additionally, a composite index of social adversity was derived from measures of perceived discrimination, socioeconomic status, financial restriction to receiving medical care, and perceived neighborhood characteristics. Multiple regression was used to test whether relationships between adversity and depressive symptoms differed as a function of HIV-status and racial/ethnic identity. Results A significant three-way interaction between social adversity, HIV-status, and racial/ethnic identity indicated that there was a direct relationship between adversity and depressive symptoms for HIV-positive (HIV+) African Americans but not for HIV-negative (HIV-) African Americans, HIV+ Caucasians, or HIV- Caucasians. Further, HIV+ African Americans evidenced a significantly greater relationship between adversity and depressive symptoms, as compared to HIV- African Americans but not as compared to other groups. Conclusions The findings suggest that HIV+ African Americans may be at risk for higher depressive symptoms amidst adversity, highlighting the importance of evaluating intersectional identities/statuses in the context of mental health. PMID:27929330

Differential relationships between social adversity and depressive symptoms by HIV status and racial/ethnic identity.

PubMed

Williamson, Timothy J; Mahmood, Zanjbeel; Kuhn, Taylor P; Thames, April D

2017-02-01

Historically marginalized groups are likely to be exposed to social adversity, which predicts important mental health outcomes (e.g., depression). Despite the well-established relationship between adversity and poor health, few studies have examined how adversity differentially predicts mental health among people living with multiple, co-occurring marginalized identities or statuses. The current study fills this gap by examining whether relationships between social adversity and depressive symptoms differed between those living with or without a stigmatized disease (i.e., HIV) and/or marginalized racial/ethnic identity (i.e., African American). A community sample of men and women (N = 149) completed questionnaires assessing demographics and depressive symptoms. Additionally, a composite index of social adversity was derived from measures of perceived discrimination, socioeconomic status, financial restriction to receiving medical care, and perceived neighborhood characteristics. Multiple regression was used to test whether relationships between adversity and depressive symptoms differed as a function of HIV status and racial/ethnic identity. A significant 3-way interaction between social adversity, HIV status, and racial/ethnic identity indicated that there was a direct relationship between adversity and depressive symptoms for HIV-positive (HIV+) African Americans but not for HIV-negative (HIV-) African Americans, HIV+ Caucasians, or HIV- Caucasians. Further, HIV+ African Americans evidenced a significantly greater relationship between adversity and depressive symptoms compared with HIV- African Americans, but not compared with other groups. The findings suggest that HIV+ African Americans may be at risk for higher depressive symptoms amid adversity, highlighting the importance of evaluating intersectional identities/statuses in the context of mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Right Atrial Deformation in Predicting Outcomes in Pediatric Pulmonary Hypertension.

PubMed

Jone, Pei-Ni; Schäfer, Michal; Li, Ling; Craft, Mary; Ivy, D Dunbar; Kutty, Shelby

2017-12-01

Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes. Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls ( P <0.001). There were significant associations between RA function with invasive hemodynamics ( P <0.01). RA reservoir, pump function, the rate of RA filling, and atrial minimum volume predicted adverse clinical outcomes (hazard ratio [HR], 0.15; confidence interval [CI], 0.03-0.73; P <0.01; HR, 0.05; CI, 0.003-0.43; P <0.004; HR, 0.04; CI, 0.006-0.56; P <0.01; and HR, 8.6; CI, 1.6-37.2; P <0.01, respectively). RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH. © 2017 American Heart Association, Inc.

Early Life Stress, MAOA, and Gene-Environment Interactions Predict Behavioral Disinhibition in Children

PubMed Central

Enoch, Mary-Anne; Steer, Colin D.; Newman, Timothy K.; Gibson, Nerea; Goldman, David

2009-01-01

Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth – 3 years) stressors to influence behavior in pre-pubertal children. The Avon Longitudinal Study of Parents and Children, U.K., is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years. In both sexes, exposure to family adversity and stressful life events in the first three years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3 ½ years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1 ½ and 2 ½ years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity. In a general population sample of pre-pubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR - stressful life event interactions specifically predicted hyperactivity. PMID:19804559

Comparison between Frailty Index of Deficit Accumulation and Phenotypic Model to Predict Risk of Falls: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort

PubMed Central

Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra

2015-01-01

Objectives To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years. Methods Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. Results The FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively. Conclusions The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings. PMID:25764521

Comparison between frailty index of deficit accumulation and phenotypic model to predict risk of falls: data from the global longitudinal study of osteoporosis in women (GLOW) Hamilton cohort.

PubMed

Li, Guowei; Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra; Adachi, Jonathan D

2015-01-01

To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years. Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. The FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively. The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.

Blunted Diurnal Cortisol Activity in Healthy Adults with Childhood Adversity.

PubMed

Kuras, Yuliya I; Assaf, Naomi; Thoma, Myriam V; Gianferante, Danielle; Hanlin, Luke; Chen, Xuejie; Fiksdal, Alexander; Rohleder, Nicolas

2017-01-01

Childhood adversity, such as neglect, or physical, emotional, or sexual abuse, is prevalent in the U.S. and worldwide, and connected to an elevated incidence of disease in adulthood. A pathway in this relationship might be altered hypothalamic-pituitary-adrenal (HPA) axis functioning, as a result of differential hippocampal development in early life. A blunted diurnal cortisol slope is a precursor for many disorders. While studies have focused on HPA reactivity in relation to childhood adversity, there has been markedly less research on basal HPA functioning in those with low-to-moderate adversity. Based on previous research, we hypothesized that adults with low-to-moderate childhood adversity would have altered HPA axis functioning, as evidenced by a blunted diurnal cortisol slope and altered cortisol awakening response (CAR). Healthy adults aged 18-65 ( n = 61 adults; 31 males and 30 females) completed the Childhood Trauma Questionnaire. Participants provided at-home saliva samples on two consecutive days at wake-up, and 30 min, 1, 4, 9, and 13 h later; samples were averaged over the 2 days. We found that low-to-moderate childhood adversity predicted lower morning cortisol (β = -0.34, p = 0.007, R 2 = 0.21), as well as a blunted cortisol slope (β = 2.97, p = 0.004, R 2 = 0.22), but found no association with CAR (β = 0.19, p = 0.14, R 2 = 0.12). Overall, we found that in healthy participants, low-to-moderate adversity in childhood is associated with altered basal HPA activity in adulthood. Our findings indicate that even low levels of childhood adversity may predispose individuals to disease associated with HPA dysregulation in later life.

Setting the stage for chronic health problems: cumulative childhood adversity among homeless adults with mental illness in Vancouver, British Columbia.

PubMed

Patterson, Michelle L; Moniruzzaman, Akm; Somers, Julian M

2014-04-12

It is well documented that childhood abuse, neglect and household dysfunction are disproportionately present in the backgrounds of homeless adults, and that these experiences adversely impact child development and a wide range of adult outcomes. However, few studies have examined the cumulative impact of adverse childhood experiences on homeless adults with mental illness. This study examines adverse events in childhood as predictors of duration of homelessness, psychiatric and substance use disorders, and physical health in a sample of homeless adults with mental illness. This study was conducted using baseline data from a randomized controlled trial in Vancouver, British Columbia for participants who completed the Adverse Childhood Experiences (ACE) scale at 18 months follow-up (n=364). Primary outcomes included current mental disorders; substance use including type, frequency and severity; physical health; duration of homelessness; and vocational functioning. In multivariable regression models, ACE total score independently predicted a range of mental health, physical health, and substance use problems, and marginally predicted duration of homelessness. Adverse childhood experiences are overrepresented among homeless adults with complex comorbidities and chronic homelessness. Our findings are consistent with a growing body of literature indicating that childhood traumas are potent risk factors for a number of adult health and psychiatric problems, particularly substance use problems. Results are discussed in the context of cumulative adversity and self-trauma theory. This trial has been registered with the International Standard Randomized Control Trial Number Register and assigned ISRCTN42520374.

MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity.

PubMed

Molet, Jenny; Maras, Pamela M; Kinney-Lang, Eli; Harris, Neil G; Rashid, Faisal; Ivy, Autumn S; Solodkin, Ana; Obenaus, Andre; Baram, Tallie Z

2016-12-01

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

PubMed Central

Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

2016-01-01

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis.

PubMed

Shaw, Michael T; Pawlak, Natalie O; Frontario, Ariana; Sherman, Kathleen; Krupp, Lauren B; Charvet, Leigh E

2017-01-01

Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset ( r  = -0.30, p  = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) ( r  = -0.25, p  = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

PubMed

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Adverse Childhood Experiences Predict Alcohol Consumption Patterns Among Kenyan Mothers.

PubMed

Goodman, Michael L; Grouls, Astrid; Chen, Catherine X; Keiser, Philip H; Gitari, Stanley

2017-04-16

We analyze whether adverse childhood experiences predict weekly alcohol consumption patterns of Kenyan mothers and their partners. Randomly selected respondents (n = 1,976) were asked about adverse childhood experiences and alcohol consumption patterns for themselves and their partners. Fixed effect models were used to determine odds of reporting weekly alcohol consumption and the number of beverages typically consumed, controlling for wealth, age, education, and partner alcohol consumption. Cumulative adverse childhood experiences predicted higher odds of weekly alcohol consumption of the respondent and her partner. Childhood exposure to physical abuse, emotional neglect, and mental illness in the household significantly increased odds of weekly alcohol consumption by the respondent. More drinks consumed per typical session were higher among respondents with more cumulative adversities. Physical and emotional abuse significantly predicted number of drinks typically consumed by the respondent. To our knowledge, this is the first study to explore and find associations between adverse childhood experiences and alcohol consumption in Kenya. Consistent with high-income settings, exposure to childhood adversities predicted greater alcohol consumption among Kenyan women.

Can we predict functional decline in hospitalized older people admitted through the emergency department? Reanalysis of a predictive tool ten years after its conception.

PubMed

De Brauwer, Isabelle; Cornette, Pascale; Boland, Benoît; Verschuren, Franck; D'Hoore, William

2017-05-12

In the Emergency Department (ED), early and rapid identification of older people at risk of adverse outcomes, who could best benefit from complex geriatric intervention, would avoid wasting time, especially in terms of prevention of adverse outcomes, and ensure optimal orientation of vulnerable patients. We wanted to test the predictive ability of a screening tool assessing risk of functional decline (FD), named SHERPA, 10 years after its conception, and to assess the added value of other clinical or biological factors associated with FD. A prospective cohort study of older patients (n = 305, ≥ 75 years) admitted through the emergency department, for at least 48 h in non-geriatric wards (mean age 82.5 ± 4.9, 55% women). SHERPA variables (i.e. age, pre-admission instrumental Activity of Daily Living (ADL) status, falls within a year, self-rated health and 21-point MMSE) were collected within 48 h of admission, along with socio-demographic, medical and biological data. Functional status was followed at 3 months by phone. FD was defined as a decrease at 3 months of at least one point in the pre-admission basic ADL score. Predictive ability of SHERPA was assessed using c-statistic, predictive values and likelihood ratios. Measures of discrimination improvement were Net Reclassification Improvement and Integrated Discrimination Improvement. One hundred and five patients (34%) developed 3-month FD. Predictive ability of SHERPA decreased dramatically over 10 years (c = 0.73 vs. 0.64). Only two of its constitutive variables, i.e. falls and instrumental ADL, were significant in logistic regression analysis for functional decline, while 21-point MMSE was kept in the model for clinical relevance. Demographic, comorbidity or laboratory data available upon admission did not improve the SHERPA predictive yield. Prediction of FD with SHERPA is difficult, but predictive factors, i.e. falls, pre-existing functional limitation and cognitive impairment, stay consistent across time and with literature. As accuracy of SHERPA and others existing screening tools for FD is moderate, using these predictors as flags instead of using composite scales can be a way to screen for high-risk patients.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

PubMed

Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

2016-05-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging

PubMed Central

Voss, Michelle W.; Weng, Timothy B.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P.; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

2015-01-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

Associations between early life adversity and executive function in children adopted internationally from orphanages

PubMed Central

Hostinar, Camelia E.; Stellern, Sarah A.; Schaefer, Catherine; Carlson, Stephanie M.; Gunnar, Megan R.

2012-01-01

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery. PMID:23047689

Associations between early life adversity and executive function in children adopted internationally from orphanages.

PubMed

Hostinar, Camelia E; Stellern, Sarah A; Schaefer, Catherine; Carlson, Stephanie M; Gunnar, Megan R

2012-10-16

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

In vitro function of the aryl hydrocarbon receptor predicts in vivo sensitivity of oviparous vertebrates to dioxin-like compounds

EPA Science Inventory

Differences in sensitivity to dioxin-like compounds (DLCs) among species and taxa presents a major challenge to ecological risk assessments. Activation of the aryl hydrocarbon receptor (AHR) regulates adverse effects associated with exposure to DLCs in vertebrates. Prior investig...

Handgrip Strength Predicts Functional Decline at Discharge in Hospitalized Male Elderly: A Hospital Cohort Study

PubMed Central

García-Peña, Carmen; García-Fabela, Luis C.; Gutiérrez-Robledo, Luis M.; García-González, Jose J.; Arango-Lopera, Victoria E.; Pérez-Zepeda, Mario U.

2013-01-01

Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. The aim of this study was to determine if handgrip strength measured upon admission to an acute care facility would predict functional decline (either incident or worsening of preexisting) at discharge among older Mexican, stratified by gender. In addition, cutoff points as a function of specificity would be determined. A cohort study was conducted in two hospitals in Mexico City. The primary endpoint was functional decline on discharge, defined as a 30-point reduction in the Barthel Index score from that of the baseline score. Handgrip strength along with other variables was measured at initial assessment, including: instrumental activities of daily living, cognition, depressive symptoms, delirium, hospitalization length and quality of life. All analyses were stratified by gender. Logistic regression to test independent association between handgrip strength and functional decline was performed, along with estimation of handgrip strength test values (specificity, sensitivity, area under the curve, etc.). A total of 223 patients admitted to an acute care facility between 2007 and 2009 were recruited. A total of 55 patients (24.7%) had functional decline, 23.46% in male and 25.6% in women. Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79–0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and intervene consequently. PMID:23936113

Change in motor function and adverse health outcomes in older African-Americans.

PubMed

Buchman, Aron S; Wilson, Robert S; Leurgans, Sue E; Bennett, David A; Barnes, Lisa L

2015-10-01

We tested whether declining motor function accelerates with age in older African-Americans. Eleven motor performances were assessed annually in 513 older African-Americans. During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/year (Estimate, -0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p's<0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African-Americans. Copyright © 2015 Elsevier Inc. All rights reserved.

Stressful life events as predictors of functioning: findings from the Collaborative Longitudinal Personality Disorders Study

PubMed Central

Pagano, M. E.; Skodol, A. E.; Stout, R. L.; Shea, M. T.; Yen, S.; Grilo, C. M.; Sanislow, C. A.; Bender, D. S.; McGlashan, T. H.; Zanarini, M. C.; Gunderson, J. G.

2008-01-01

Objective Although much attention has been given to the effects of adverse childhood experiences on the development of personality disorders (PDs), we know far less about how recent life events influence the ongoing course of functioning. We examined the extent to which PD subjects differ in rates of life events and the extent to which life events impact psychosocial functioning. Method A total of 633 subjects were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS), a multi-site study of four personality disorders – schizotypal (STPD), borderline (BPD), avoidant (AVPD), obsessive-compulsive (OCPD) – and a comparison group of major depressive disorders (MDD) without PD. Results Borderline personality disorder subjects reported significantly more total negative life events than other PDs or subjects with MDD. Negative events, especially interpersonal events, predicted decreased psychosocial functioning over time. Conclusion Our findings indicate higher rates of negative events in subjects with more severe PDs and suggest that negative life events adversely impact multiple areas of psychosocial functioning. PMID:15521826

Change in Motor Function and Adverse Health Outcomes in Older African Americas

PubMed Central

Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Barnes, Lisa L.

2015-01-01

Objective We tested whether declining motor function accelerates with age in older African Americans. Methods Eleven motor performances were assessed annually in 513 older African Americans. Results During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/yr (Estimate, −0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p’s <0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. Conclusions The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African Americans. PMID:26209439

ACCEPT: Introduction of the Adverse Condition and Critical Event Prediction Toolbox

NASA Technical Reports Server (NTRS)

Martin, Rodney A.; Santanu, Das; Janakiraman, Vijay Manikandan; Hosein, Stefan

2015-01-01

The prediction of anomalies or adverse events is a challenging task, and there are a variety of methods which can be used to address the problem. In this paper, we introduce a generic framework developed in MATLAB (sup registered mark) called ACCEPT (Adverse Condition and Critical Event Prediction Toolbox). ACCEPT is an architectural framework designed to compare and contrast the performance of a variety of machine learning and early warning algorithms, and tests the capability of these algorithms to robustly predict the onset of adverse events in any time-series data generating systems or processes.

Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals

EPA Science Inventory

There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...

Does the Use of Connective Words in Written Assessments Predict High School Students' Reading and Writing Achievement?

ERIC Educational Resources Information Center

Duggleby, Sandra J.; Tang, Wei; Kuo-Newhouse, Amy

2016-01-01

This study examined the relationship between ninth-grade students' use of connectives (temporal, causal, adversative, and additive) in functional writing and performance on standards-based/criterion-referenced measures of reading and writing. Specifically, structural equation modeling (SEM) techniques were used to examine the relationship between…

The Effects of Sleep Deprivation on Item and Associative Recognition Memory

ERIC Educational Resources Information Center

Ratcliff, Roger; Van Dongen, Hans P. A.

2018-01-01

Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item…

Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

PubMed

Mangoni, Arduino A

2012-05-01

Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study

PubMed Central

Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

2015-01-01

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning. PMID:26506054

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

Cumulative early life adversity predicts longevity in wild baboons

PubMed Central

Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

2016-01-01

In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

Monoamine oxidase A genotype, childhood adversity, and criminal behavior in an incarcerated sample.

PubMed

Armstrong, Todd A; Boutwell, Brian B; Flores, Shahida; Symonds, Mary; Keller, Shawn; Gangitano, David A

2014-08-01

A number of studies have found a functional variable number tandem repeat polymorphism in the upstream regulatory region of the monoamine oxidase A gene (MAOA-uVNTR) interacts with childhood adversity to increase risk for antisocial behavior. Several studies have also reported null findings. Here, we examine the association between MAOA-uVNTR genotype, childhood adversity, and criminal activity in a sample of 99 male volunteers who were incarcerated in a large city jail in the Southern United States. MAOA-uVNTR genotypes were obtained from DNA extracted from buccal swabs. Criminal activity in the year before incarceration and childhood adversity were measured with self-report surveys. Violent arrest rates and property arrest rates were quantified with official records of arrest and accounted for periods of incarceration in local and state correctional facilities. The low expressing allele of the MAOA-uVNTR genotype (MAOAL) interacted with abuse to predict self-reports of less serious criminal and delinquent behavior and had a direct association with serious criminal activity. MAOAL genotype interacted with parental criminality to predict self-reports of serious criminal behavior, property arrest rates, and violent arrest rates. The findings suggest that crime prevention efforts may be improved through attention to the neurodevelopmental consequence of gene-by-environment interactions.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

PubMed

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P < 0.0001), and correctly predicted objective response rate ( P = 0.0044) as well as adverse events ( P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

PubMed Central

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-01-01

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration–time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters (ABCB1 and ABCG2), UGT1A, and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate (P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC (P < 0.0001), and correctly predicted objective response rate (P = 0.0044) as well as adverse events (P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC. PMID:29682213

Clinicopathological Features to Predict Progression of IgA Nephropathy with Mild Proteinuria.

PubMed

Chen, Ding; Liu, Jian; Duan, Shuwei; Chen, Pu; Tang, Li; Zhang, Li; Feng, Zhe; Cai, Guangyan; Wu, Jie; Chen, Xiangmei

2018-03-06

In the past, little attention has been paid to patients with IgA nephropathy (IgAN) who had minimal proteinuria upon the onset. The aim of this study was to analyze the clinicopathological features and the prognostic factors in patients with IgA nephropathy. Data of patients that had their first renal biopsy in our hospital and were diagnosed with primary IgAN with proteinuria <1 g/d from January 1995 to December 2014 were retrospectively examined. Clinical records of the clinicopathological features, renal function, and proteinuria were collected and investigated. The factors affecting the renal function and proteinuria were analyzed by Cox regression. The predictive efficiencies of clinical and pathological models were evaluated by Harrell concordance index (C-index). A total of 506 patients with IgA nephropathy were included in this study. (1) Baseline proteinuria greater than 0.5 g/d was positively associated with Oxford M, S, and T lesions. eGFR less than 90 mL/min/1.73 m2 were positively associated with Oxford T. (2) In the follow-up with a median of 50 months, 82 patients (16.2%) achieved complete clinical remission (CCR), whereas 54 patients (10.6%) showed an increase in creatinine by more than 50% (not progressing to end-stage renal disease). The cumulative proportion of creatinine increased >50%, and the values obtained by life-table analysis in 10, 15, and 20 years were 15%, 21%, and 22%, respectively. Significant differences were found in baseline age, proteinuria, and Oxford T between the group of creatinine increase >50% and the CCR group. (4) Multivariate COX regression showed that baseline age and proteinuria > 0.5 g/d were independent risk factors of adverse outcome. C-index suggested that the clinical model was more effective than the pathological models in predicting endpoint events. (5) Effect of the mean value during the follow-up on adverse endpoint events: Multivariate COX regression found that the mean proteinuria during follow-up was an independent influencing factor for the increase of creatinine by more than 50%. (1) Proteinuria > 0.5g/d and eGFR < 90 mL/min/1.73 m2 may predict more severe pathological changes; (2) With the increase in age and baseline proteinuria, the risks of adverse endpoint events would increase significantly; (3) Pathology could roughly predict the adverse endpoint events but is less efficient than the clinical indicators; (4) Data during follow-up suggested that the patients should regularly test their renal function and proactively control their proteinuria. © 2018 The Author(s). Published by S. Karger AG, Basel.

Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R) III: associations with functional impairment related to DSM-IV disorders.

PubMed

McLaughlin, K A; Green, J G; Gruber, M J; Sampson, N A; Zaslavsky, A M; Kessler, R C

2010-05-01

Despite evidence that childhood adversities (CAs) are associated with increased risk of mental disorders, little is known about their associations with disorder-related impairment. We report the associations between CAs and functional impairment associated with 12-month DSM-IV disorders in a national sample. We used data from the US National Comorbidity Survey Replication (NCS-R). Respondents completed diagnostic interviews that assessed 12-month DSM-IV disorder prevalence and impairment. Associations of 12 retrospectively reported CAs with impairment among cases (n=2242) were assessed using multiple regression analysis. Impairment measures included a dichotomous measure of classification in the severe range of impairment on the Sheehan Disability Scale (SDS) and a measure of self-reported number of days out of role due to emotional problems in the past 12 months. CAs were positively and significantly associated with impairment. Predictive effects of CAs on the SDS were particularly pronounced for anxiety disorders and were significant in predicting increased days out of role associated with mood, anxiety and disruptive behavior disorders. Predictive effects persisted throughout the life course and were not accounted for by disorder co-morbidity. CAs associated with maladaptive family functioning (MFF; parental mental illness, substance disorder, criminality, family violence, abuse, neglect) were more consistently associated with impairment than other CAs. The joint effects of co-morbid MFF CAs were significantly subadditive. Simulations suggest that CAs account for 19.6% of severely impairing disorders and 17.4% of days out of role. CAs predict greater disorder-related impairment, highlighting the ongoing clinical significance of CAs at every stage of the life course.

The Interplay among Preschool Child and Family Factors and the Development of ODD Symptoms

ERIC Educational Resources Information Center

Harvey, Elizabeth A.; Metcalfe, Lindsay A.

2012-01-01

The present study examined (a) the interactions between early behavior, early parenting, and early family adversity in predicting later oppositional defiant disorder (ODD) symptoms, and (b) the reciprocal relations between parent functioning and ODD symptoms across the preschool years. Participants were 258 three-year-old children (138 boys, 120…

Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors.

PubMed

Nicholas, Sara S; Stamilio, David M; Dicke, Jeffery M; Gray, Diana L; Macones, George A; Odibo, Anthony O

2009-10-01

The aim of this study was to determine whether prenatal variables can predict adverse neonatal outcomes in fetuses with abdominal wall defects. A retrospective cohort study that used ultrasound and neonatal records for all cases of gastroschisis and omphalocele seen over a 16-year period. Cases with adverse neonatal outcomes were compared with noncases for multiple candidate predictive factors. Univariable and multivariable statistical methods were used to develop the prediction models, and effectiveness was evaluated using the area under the receiver operating characteristic curve. Of 80 fetuses with gastroschisis, 29 (36%) had the composite adverse outcome, compared with 15 of 33 (47%) live neonates with omphalocele. Intrauterine growth restriction was the only significant variable in gastroschisis, whereas exteriorized liver was the only predictor in omphalocele. The areas under the curve for the prediction models with gastroschisis and omphalocele are 0.67 and 0.74, respectively. Intrauterine growth restriction and exteriorization of the liver are significant predictors of adverse neonatal outcome with gastroschisis and omphalocele.

Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

PubMed

Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

2013-11-01

The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

Discriminative ability of commonly used indices to predict adverse outcomes after poster lumbar fusion: a comparison of demographics, ASA, the modified Charlson Comorbidity Index, and the modified Frailty Index.

PubMed

Ondeck, Nathaniel T; Bohl, Daniel D; Bovonratwet, Patawut; McLynn, Ryan P; Cui, Jonathan J; Shultz, Blake N; Lukasiewicz, Adam M; Grauer, Jonathan N

2018-01-01

As research tools, the American Society of Anesthesiologists (ASA) physical status classification system, the modified Charlson Comorbidity Index (mCCI), and the modified Frailty Index (mFI) have been associated with complications following spine procedures. However, with respect to clinical use for various adverse outcomes, no known study has compared the predictive performance of these indices specifically following posterior lumbar fusion (PLF). This study aimed to compare the discriminative ability of ASA, mCCI, and mFI, as well as demographic factors including age, body mass index, and gender for perioperative adverse outcomes following PLF. A retrospective review of prospectively collected data was performed. Patients undergoing elective PLF with or without interbody fusion were extracted from the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (NSQIP). Perioperative adverse outcome variables assessed included the occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, and discharge to higher-level care. Patient comorbidity indices and characteristics were delineated and assessed for discriminative ability in predicting perioperative adverse outcomes using an area under the curve analysis from the receiver operating characteristics curves. In total, 16,495 patients were identified who met the inclusion criteria. The most predictive comorbidity index was ASA and demographic factor was age. Of these two factors, age had the larger discriminative ability for three out of the six adverse outcomes and ASA was the most predictive for one out of six adverse outcomes. A combination of the most predictive demographic factor and comorbidity index resulted in improvements in discriminative ability over the individual components for five of the six outcome variables. For PLF, easily obtained patient ASA and age have overall similar or better discriminative abilities for perioperative adverse outcomes than numerically tabulated indices that have multiple inputs and are harder to implement in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

By-product mutualism with evolving common enemies.

PubMed

De Jaegher, Kris

2017-05-07

The common-enemy hypothesis of by-product mutualism states that organisms cooperate when it is in their individual interests to do so, with benefits for other organisms arising as a by-product; in particular, such cooperation is hypothesized to arise when organisms face the common enemy of a sufficiently adverse environment. In an evolutionary game where two defenders can cooperate to defend a common resource, this paper analyzes the common-enemy hypothesis when adversity is endogenous, in that an attacker sets the number of attacks. As a benchmark, we first consider exogenous adversity, where adversity is not subject to evolution. In this case, the common-enemy hypothesis is predicted when the degree of complementarity between defenders' defensive efforts is sufficiently low. When the degree of complementarity is high, the hypothesis is predicted only when cooperation costs are high; when cooperation costs are instead low, a competing hypothesis is predicted, where adversity discourages cooperation. Second, we consider the case of endogenous adversity. In this case, we continue to predict the competing hypothesis for a high degree of complementarity and low cooperation costs. The common-enemy hypothesis, however, only continues to be predicted for the lowest degrees of complementarity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prospective observational study of delirium recovery trajectories and associated short-term outcomes in older adults admitted to a specialized delirium unit.

PubMed

Lam, Ching-yu; Tay, Laura; Chan, Mark; Ding, Yew Yoong; Chong, Mei Sian

2014-09-01

To describe the recovery trajectories of delirium and to determine factors predicting the course of recovery and adverse outcome. A prospective observational study. Geriatric monitoring unit (GMU), a five-bed unit specializing in managing older adults with delirium. Individuals admitted to the GMU between December 2010 and August 2012 (N = 234; mean age 84.1 ± 7.4). Information was collected on demographic characteristics; comorbidities; severity of illness; functional status; and daily cognitive, Delirium Rating Scale, Revised-98 (DRS-R98) severity, and functional scoring. Resolution of delirium, and thus GMU discharge, was determined according to clinical assessment. The primary outcome was residual subsyndromal delirium (SSD) (DRS-R98 severity ≥13) upon GMU discharge. Univariate and multivariate methods were used to determine the predictors of residual SSD and adverse outcomes (inpatient mortality and incident nursing home admission upon discharge). Participants with residual SSD had a slower recovery in terms of delirium severity, cognition, and functional status than those with no residual SSD. Residual SSD predictors included underlying dementia, admission DRS-R98 severity, DRS-R98 severity on Day 1 minus Day 3 of GMU stay, and admission modified Barthel Index. Only presence of residual SSD at discharge predicted adverse outcomes (odds ratio = 5.27, 95% confidence interval = 1.43-19.47). Individuals with residual SSD had prolonged recovery trajectory of delirium. These new insights into the recovery trajectories of delirium may help formulate early discharge planning and provide the basis for future research on delirium treatment. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

The effects of power, leadership and psychological safety on resident event reporting.

PubMed

Appelbaum, Nital P; Dow, Alan; Mazmanian, Paul E; Jundt, Dustin K; Appelbaum, Eric N

2016-03-01

Although the reporting of adverse events is a necessary first step in identifying and addressing lapses in patient safety, such events are under-reported, especially by frontline providers such as resident physicians. This study describes and tests relationships between power distance and leader inclusiveness on psychological safety and the willingness of residents to report adverse events. A total of 106 resident physicians from the departments of neurosurgery, orthopaedic surgery, emergency medicine, otolaryngology, neurology, obstetrics and gynaecology, paediatrics and general surgery in a mid-Atlantic teaching hospital were asked to complete a survey on psychological safety, perceived power distance, leader inclusiveness and intention to report adverse events. Perceived power distance (β = -0.26, standard error [SE] 0.06, 95% confidence interval [CI] -0.37 to 0.15; p < 0.001) and leader inclusiveness (β = 0.51; SE 0.07, 95% CI 0.38-0.65; p < 0.001) both significantly predicted psychological safety, which, in turn, significantly predicted intention to report adverse events (β = 0.34; SE 0.08, 95% CI 0.18-0.49; p < 0.001). Psychological safety significantly mediated the direct relationship between power distance and intention to report adverse events (indirect effect: -0.09; SE 0.02, 95% CI -0.13 to 0.04; p < 0.001). Psychological safety also significantly mediated the direct relationship between leader inclusiveness and intention to report adverse events (indirect effect: 0.17; SE 0.02, 95% CI 0.08-0.27; p = 0.001). Psychological safety was found to be a predictor of intention to report adverse events. Perceived power distance and leader inclusiveness both influenced the reporting of adverse events through the concept of psychological safety. Because adverse event reporting is shaped by relationships and culture external to the individual, it should be viewed as an organisational as much as a personal function. Supervisors and other leaders in health care should ensure that policies, procedures and leadership practices build psychological safety and minimise power distance between low- and high-status members in order to support greater reporting of adverse events. © 2016 John Wiley & Sons Ltd.

Partial and no recovery from delirium after hospital discharge predict increased adverse events.

PubMed

Cole, Martin G; McCusker, Jane; Bailey, Robert; Bonnycastle, Michael; Fung, Shek; Ciampi, Antonio; Belzile, Eric

2017-01-08

The implications of partial and no recovery from delirium after hospital discharge are not clear. We sought to explore whether partial and no recovery from delirium among recently discharged patients predicted increased adverse events (emergency room visits, hospitalisations, death) during the subsequent 3 months. Prospective study of recovery from delirium in older hospital inpatients. The Confusion Assessment Method was used to diagnose delirium in hospital and determine recovery status after discharge (T0). Adverse events were determined during the 3 months T0. Survival analysis to the first adverse event and counting process modelling for one or more adverse events were used to examine associations between recovery status (ordinal variable, 0, 1 or 2 for full, partial or no recovery, respectively) and adverse events. Of 278 hospital inpatients with delirium, 172 were discharged before the assessment of recovery status (T0). Delirium recovery status at T0 was determined for 152: 25 had full recovery, 32 had partial recovery and 95 had no recovery. Forty-four patients had at least one adverse event during the subsequent 3 months. In multivariable analysis of one or more adverse events, poorer recovery status predicted increased adverse events; the hazard ratio (HR) (95% confidence interval, CI) was 1.72 (1.09, 2.71). The association of recovery status with adverse events was stronger among patients without dementia. Partial and no recovery from delirium after hospital discharge appear to predict increased adverse events during the subsequent 3 months These findings have potentially important implications for in-hospital and post-discharge management and policy.

Dysthymic Disorder and Double Depression: Prediction of 10-Year Course Trajectories and Outcomes

PubMed Central

Klein, Daniel N.; Shankman, Stewart A.; Rose, Suzanne

2008-01-01

We sought to identify baseline predictors of 10-year course trajectories and outcomes in patients with dysthymic disorder and double depression. Eighty-seven outpatients with early-onset (< 21 years) dysthymic disorder, with or without superimposed major depression, were assessed five times at 30-month intervals for 10 years. Baseline evaluations included semi-structured diagnostic interviews for Axis I and II psychopathology and childhood adversity. Direct interview and family history data were collected on first-degree relatives. Follow-up assessments included the Longitudinal Follow-up Evaluation and Hamilton Depression Rating Scale. Using mixed effects growth curve models, univariate predictors of depression severity and functional impairment at 10-year outcome included older age, less education, concurrent anxiety disorder, greater familial loading for chronic depression, a history of a poorer maternal relationship in childhood, and a history of childhood sexual abuse. In addition, longer duration of dysthymic disorder also predicted greater impairment 10 years later. Predictors of a poorer trajectory of depressive symptoms over time included ethnicity and personality disorders; predictors of a poorer trajectory of social functioning included familial loading of chronic depression and quality of the childhood maternal relationship. Thus, demographic, clinical, family history, and early adversity variables all contribute to predicting the long term trajectory and outcome of DD. These variables should be routinely assessed in clinical evaluations and can provide clinicians with valuable prognostic information. PMID:17466334

Dysthymic disorder and double depression: prediction of 10-year course trajectories and outcomes.

PubMed

Klein, Daniel N; Shankman, Stewart A; Rose, Suzanne

2008-04-01

We sought to identify baseline predictors of 10-year course trajectories and outcomes in patients with dysthymic disorder and double depression. Eighty-seven outpatients with early-onset (<21 years) dysthymic disorder, with or without superimposed major depression, were assessed five times at 30-month intervals for 10 years. Baseline evaluations included semi-structured diagnostic interviews for Axis I and II psychopathology and childhood adversity. Direct interview and family history data were collected on first-degree relatives. Follow-up assessments included the Longitudinal Follow-up Evaluation and Hamilton Depression Rating Scale. Using mixed effects growth curve models, univariate predictors of depression severity and functional impairment at 10-year outcome included older age, less education, concurrent anxiety disorder, greater familial loading for chronic depression, a history of a poorer maternal relationship in childhood, and a history of childhood sexual abuse. In addition, longer duration of dysthymic disorder also predicted greater impairment 10 years later. Predictors of a poorer trajectory of depressive symptoms over time included ethnicity and personality disorders; predictors of a poorer trajectory of social functioning included familial loading of chronic depression and quality of the childhood maternal relationship. Thus, demographic, clinical, family history, and early adversity variables all contribute to predicting the long-term trajectory and outcome of DD. These variables should be routinely assessed in clinical evaluations and can provide clinicians with valuable prognostic information.

A clinical return-to-work rule for patients with back pain.

PubMed

Dionne, Clermont E; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R; Larocque, Isabelle

2005-06-07

Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18-64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was "return to work in good health" at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%- 94%). A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome.

A clinical return-to-work rule for patients with back pain

PubMed Central

Dionne, Clermont E.; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R.; Larocque, Isabelle

2005-01-01

Background Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. Methods This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18–64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was “return to work in good health” at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. Results The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%– 94%). Interpretation A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome. PMID:15939915

Testing and testing positive: childhood adversities and later life HIV status among Kenyan women and their partners.

PubMed

Goodman, Michael L; Raimer-Goodman, Lauren; Chen, Catherine X; Grouls, Astrid; Gitari, Stanley; Keiser, Philip H

2017-12-01

Adverse childhood experiences are a critical feature of lifelong health. No research assesses whether childhood adversities predict HIV-testing behaviors, and little research analyzes childhood adversities and later life HIV status in sub-Saharan Africa. We use regression models with cross-sectional data from a representative sample (n = 1974) to analyze whether adverse childhood experiences, separately or as cumulative exposures, predict reports of later life HIV testing and testing HIV+ among semi-rural Kenyan women and their partners. No significant correlation was observed between thirteen cumulative childhood adversities and reporting prior HIV testing for respondent or partner. Separately, childhood sexual abuse and emotional neglect predicted lower odds of reporting having previously been tested for HIV. Witnessing household violence during one's childhood predicted significantly higher odds of reporting HIV+. Sexual abuse predicted higher odds of reporting a partner tested HIV+. Preventing sexual abuse and household violence may improve HIV testing and test outcomes among Kenyan women. More research is required to understand pathways between adverse childhood experiences and partner selection within Kenya and sub-Saharan Africa, and data presented here suggest understanding pathways may help improve HIV outcomes. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of ivacaftor in patients with advanced cystic fibrosis and a G551D-CFTR mutation: Safety and efficacy in an expanded access program in the United States.

PubMed

Taylor-Cousar, Jennifer; Niknian, Minoo; Gilmartin, Geoffrey; Pilewski, Joseph M

2016-01-01

Ivacaftor is the first therapeutic agent approved for the treatment of cystic fibrosis (CF) that targets the underlying molecular defect. Patients with severe lung disease were excluded from the randomized Phase 3 trials. This open-label study was designed to provide ivacaftor to patients in critical medical need prior to commercial product availability. CF patients aged ≥6 years with a G551D-CFTR mutation and FEV1 ≤ 40% predicted or listed for lung transplant received ivacaftor 150 mg every 12 h. The primary endpoint was safety as determined by adverse events. Secondary endpoints included assessment of lung function and weight. The rate of serious adverse events was consistent with disease severity. At 24 weeks of treatment with ivacaftor, there was a mean absolute increase in percent predicted FEV1 of 5.5 percentage points and a 3.3 kg mean absolute increase in weight from baseline. In patients with severe lung disease, ivacaftor was well tolerated and was associated with improved lung function and weight gain. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Computationally predicted Adverse Outcome Pathway networks for liver-related diseases using publicly available data sources: Case studies and lessons learned

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework summarizes key information about mechanistic events leading to an adverse health or ecological outcome. In recent years computationally predicted AOPs (cpAOP) making use of publicly available data have been proposed as a means of accele...

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

PubMed Central

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Maternal employment and the health of low-income young children.

PubMed

Gennetian, Lisa A; Hill, Heather D; London, Andrew S; Lopoo, Leonard M

2010-05-01

This study examines whether maternal employment affects the health status of low-income, elementary-school-aged children using instrumental variables estimation and experimental data from a welfare-to-work program implemented in the early 1990s. Maternal report of child health status is predicted as a function of exogenous variation in maternal employment associated with random assignment to the experimental group. IV estimates show a modest adverse effect of maternal employment on children's health. Making use of data from another welfare-to-work program we propose that any adverse effect on child health may be tempered by increased family income and access to public health insurance coverage, findings with direct relevance to a number of current policy discussions. In a secondary analysis using fixed effects techniques on longitudinal survey data collected in 1998 and 2001, we find a comparable adverse effect of maternal employment on child health that supports the external validity of our primary result.

Cumulative contextual and individual disadvantages over the life course and adult functional somatic symptoms in Sweden.

PubMed

Gustafsson, Per E; Hammarström, Anne; San Sebastian, Miguel

2015-08-01

Disadvantage, originating in one's residential context or in one's past life course, has been shown to impact on health in adulthood. There is however little research on the accumulated health impact of both neighbourhood and individual conditions over the life course. This study aims to examine whether the accumulation of contextual and individual disadvantages from adolescence to middle-age predicts functional somatic symptoms (FSS) in middle-age, taking baseline health into account. The sample is the age 16, 21, 30 and 42 surveys of the prospective Northern Swedish Cohort, with analytical sample size n = 910 (85% of the original cohort). FSS at age 16 and 42, and cumulative socioeconomic disadvantage, social adversity and material adversity between 16 and 42 years were operationalized from questionnaires, and cumulative neighbourhood disadvantage between 16 and 42 years from register data. Results showed accumulation of disadvantages jointly explained 9-12% of FSS variance. In the total sample, cumulative neighbourhood and socioeconomic disadvantage significantly predicted FSS at age 42 in the total sample. In women, neighbourhood disadvantage but not socioeconomic disadvantage contributed significantly, whereas in men, socioeconomic but not neighbourhood disadvantage contributed significantly. In all analyses, associations were largely explained by the parallel accumulation of social and material adversities, but not by symptoms at baseline. In conclusion, the accumulation of diverse forms of disadvantages together plays an important role for somatic complaints in adulthood, independently of baseline health. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Ultrasound predictors of neonatal outcome in intrauterine growth restriction.

PubMed

Craigo, S D; Beach, M L; Harvey-Wilkes, K B; D'Alton, M E

1996-11-01

Our purpose was to assess the value of commonly performed ultrasound parameters in predicting neonatal outcome of fetuses with intrauterine growth restriction (IUGR). One hundred twenty-seven patients were identified on ultrasound examination to have IUGR. Estimated weight percentile, amniotic fluid volume, umbilical artery Doppler velocimetry, and head circumference/abdominal circumference ratio were compared with neonatal outcome. Thirty infants had severely adverse courses. The degree of growth restriction was strongly associated with adverse outcome and neonatal death. Umbilical artery Doppler waveforms with absent or reverse end-diastolic flow were predicted of neonatal death, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and adverse outcome in general. Oligohydramnios was predictive of adverse outcome and neonatal death. Logistic regression also showed that absent or reverse end-diastolic flow and oligohydramnios were independent predictors of adverse outcome. Ultrasound findings of low estimated weight percentile, absent or reverse end-diastolic umbilical blood flow, and oligohydramnios are independent predictors of adverse neonatal outcome of growth restricted fetuses.

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience from a German tertiary referral center for interstitial lung diseases.

PubMed

Oltmanns, Ute; Kahn, Nicolas; Palmowski, Karin; Träger, Annette; Wenz, Heinrich; Heussel, Claus Peter; Schnabel, Philipp A; Puderbach, Michael; Wiebel, Matthias; Ehlers-Tenenbaum, Svenja; Warth, Arne; Herth, Felix J F; Kreuter, Michael

2014-01-01

Pirfenidone is a novel antifibrotic drug for the treatment of mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, adverse events may offset treatment benefits and compliance. To assess recent course of disease, adverse events and compliance in patients who started pirfenidone. In an observational cohort study, 63 patients with mild-to-moderate IPF who started pirfenidone between May 2011 and June 2013 were reviewed. Pulmonary function, adverse events and treatment compliance were recorded at each clinic visit. Disease progression was defined as a reduction of vital capacity ≥10% and/or diffusion capacity (DLCO) ≥15%. Follow-up time on pirfenidone treatment was 11 (±7) months. Sixty-six percent of the patients continued with pirfenidone monotherapy and 34% of the patients received pirfenidone combined with corticosteroids (CCS) and/or N-acetylcysteine (NAC). There was a nonsignificant reduction in mean decline of percent predicted forced vital capacity after treatment start (0.7 ± 10.9%) compared to the pretreatment period (6.6 ± 6.7%, p = 0.098). Sixty-two percent of the patients had stable disease on pirfenidone treatment. Adverse events affected 85% of the patients, leading to discontinuation of pirfenidone in 20%. Adverse events and treatment discontinuation were seen more frequently in patients with concomitant CCS and/or NAC treatment. Adverse events affect the majority of patients treated with pirfenidone, but are mostly manageable with supportive measures. In this heterogeneous patient group, a nonsignificant effect of pirfenidone treatment on pulmonary function was seen, underlining the need for more data on patient selection criteria and efficacy of pirfenidone, particularly in patients with coexistent emphysema and concomitant NAC/CCS treatment.

Multi-modal measurement of the myelin-to-axon diameter g-ratio in preterm-born neonates and adult controls.

PubMed

Melbourne, Andrew; Eaton-Rosen, Zach; De Vita, Enrico; Bainbridge, Alan; Cardoso, Manuel Jorge; Price, David; Cady, Ernest; Kendall, Giles S; Robertson, Nicola J; Marlow, Neil; Ourselin, Sébastien

2014-01-01

Infants born prematurely are at increased risk of adverse functional outcome. The measurement of white matter tissue composition and structure can help predict functional performance and this motivates the search for new multi-modal imaging biomarkers. In this work we develop a novel combined biomarker from diffusion MRI and multi-component T2 relaxation measurements in a group of infants born very preterm and scanned between 30 and 40 weeks equivalent gestational age. We also investigate this biomarker on a group of seven adult controls, using a multi-modal joint model-fitting strategy. The proposed emergent biomarker is tentatively related to axonal energetic efficiency (in terms of axonal membrane charge storage) and conduction velocity and is thus linked to the tissue electrical properties, giving it a good theoretical justification as a predictive measurement of functional outcome.

Prenatal stress effects in a wild, long-lived primate: predictive adaptive responses in an unpredictable environment.

PubMed

Berghänel, Andreas; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

2016-09-28

Prenatal maternal stress affects offspring phenotype in numerous species including humans, but it is debated whether these effects are evolutionarily adaptive. Relating stress to adverse conditions, current explanations invoke either short-term developmental constraints on offspring phenotype resulting in decelerated growth to avoid starvation, or long-term predictive adaptive responses (PARs) resulting in accelerated growth and reproduction in response to reduced life expectancies. Two PAR subtypes were proposed, acting either on predicted internal somatic states or predicted external environmental conditions, but because both affect phenotypes similarly, they are largely indistinguishable. Only external (not internal) PARs rely on high environmental stability particularly in long-lived species. We report on a crucial test case in a wild long-lived mammal, the Assamese macaque (Macaca assamensis), which evolved and lives in an unpredictable environment where external PARs are probably not advantageous. We quantified food availability, growth, motor skills, maternal caretaking style and maternal physiological stress from faecal glucocorticoid measures. Prenatal maternal stress was negatively correlated to prenatal food availability and led to accelerated offspring growth accompanied by decelerated motor skill acquisition and reduced immune function. These results support the 'internal PAR' theory, which stresses the role of stable adverse internal somatic states rather than stable external environments. © 2016 The Author(s).

Admission factors can predict the need for ICU monitoring in gallstone pancreatitis.

PubMed

Arnell, T D; de Virgilio, C; Chang, L; Bongard, F; Stabile, B E

1996-10-01

The purpose was 1) to prospectively determine the prevalence of adverse events necessitating intensive care unit (ICU) monitoring in gallstone pancreatitis (GP) and 2) To identify admission prognostic indicators that predict the need for ICU unit monitoring. Prospective laboratory data, physiologic parameters, and APACHE II scores were gathered on 102 patients with GP over 14 months. Adverse events were defined as cardiac, respiratory, or renal failure, gastrointestinal bleeding, stroke, sepsis, and necrotizing pancreatitis. Patients were divided into Group 1 (no adverse events, n=95) and Group 2 (adverse events, n=7). There were no deaths and 7 (7%) adverse events, including necrotizing pancreatitis (3), cholangitis (2), and cardiac (2). APACHE 11 > or = 5 (P < 0.005), blood urea nitrogen (BUN) > or = 12 mmol/L (P < 0.005), white blood cell count (WBC) > or = 14.5 x 10(9)/L, (P < 0.001), heart rate > or = 100 bpm (P < 0.001), and glucose > or = 150 mg/dL (P < 0.005) were each independent predictors of adverse events. The sensitivity and specificity of these criteria for predicting severe complications requiring ICU care varied from 71 to 86 per cent and 78 to 87 per cent, respectively. The prevalence of adverse events necessitating ICU care in GP patients is low. Glucose, BUN, WBC, heart rate, and APACHE II scores are independent predictors of adverse events necessitating ICU care. Single criteria predicting the need for ICU care on admission are readily available on admission.

Do causal concentration-response functions exist? A critical review of associational and causal relations between fine particulate matter and mortality.

PubMed

Cox, Louis Anthony Tony

2017-08-01

Concentration-response (C-R) functions relating concentrations of pollutants in ambient air to mortality risks or other adverse health effects provide the basis for many public health risk assessments, benefits estimates for clean air regulations, and recommendations for revisions to existing air quality standards. The assumption that C-R functions relating levels of exposure and levels of response estimated from historical data usefully predict how future changes in concentrations would change risks has seldom been carefully tested. This paper critically reviews literature on C-R functions for fine particulate matter (PM2.5) and mortality risks. We find that most of them describe historical associations rather than valid causal models for predicting effects of interventions that change concentrations. The few papers that explicitly attempt to model causality rely on unverified modeling assumptions, casting doubt on their predictions about effects of interventions. A large literature on modern causal inference algorithms for observational data has been little used in C-R modeling. Applying these methods to publicly available data from Boston and the South Coast Air Quality Management District around Los Angeles shows that C-R functions estimated for one do not hold for the other. Changes in month-specific PM2.5 concentrations from one year to the next do not help to predict corresponding changes in average elderly mortality rates in either location. Thus, the assumption that estimated C-R relations predict effects of pollution-reducing interventions may not be true. Better causal modeling methods are needed to better predict how reducing air pollution would affect public health.

Serum creatinine role in predicting outcome after cardiac surgery beyond acute kidney injury

PubMed Central

Najafi, Mahdi

2014-01-01

Serum creatinine is still the most important determinant in the assessment of perioperative renal function and in the prediction of adverse outcome in cardiac surgery. Many biomarkers have been studied to date; still, there is no surrogate for serum creatinine measurement in clinical practice because it is feasible and inexpensive. High levels of serum creatinine and its equivalents have been the most important preoperative risk factor for postoperative renal injury. Moreover, creatinine is the mainstay in predicting risk models and risk factor reduction has enhanced its importance in outcome prediction. The future perspective is the development of new definitions and novel tools for the early diagnosis of acute kidney injury largely based on serum creatinine and a panel of novel biomarkers. PMID:25276301

Child maltreatment, parent alcohol and drug-related problems, polydrug problems, and parenting practices: a test of gender differences and four theoretical perspectives.

PubMed

Locke, Thomas F; Newcomb, Michael

2004-03-01

The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting and practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting.

Applications of a new wall function to turbulent flow computations

NASA Astrophysics Data System (ADS)

Chen, Y. S.

1986-01-01

A new wall function approach is developed based on a wall law suitable for incompressible turbulent boundary layers under strong adverse pressure gradients. This wall law was derived from a one-dimensional analysis of the turbulent kinetic energy equation with gradient diffusion concept employed in modeling the near-wall shear stress gradient. Numerical testing cases for the present wall functions include turbulent separating flows around an airfoil and turbulent recirculating flows in several confined regions. Improvements on the predictions using the present wall functions are illustrated. For cases of internal recirculating flows, one modification factor for improving the performance of the k-epsilon turbulence model in the flow recirculation regions is also included.

Metabolites as Biomarkers of Adverse Reactions Following Vaccination: A Pilot Study using Nuclear Magnetic Resonance Metabolomics

PubMed Central

McClenathan, Bruce M.; Stewart, Delisha A.; Spooner, Christina E.; Pathmasiri, Wimal W.; Burgess, Jason P.; McRitchie, Susan L.; Choi, Y. Sammy; Sumner, Susan C.J.

2017-01-01

An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. PMID:28169076

Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics.

PubMed

McClenathan, Bruce M; Stewart, Delisha A; Spooner, Christina E; Pathmasiri, Wimal W; Burgess, Jason P; McRitchie, Susan L; Choi, Y Sammy; Sumner, Susan C J

2017-03-01

An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1 H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. Published by Elsevier Ltd.

[Suicidal behaviors among young adults: risk factors during development from early childhood to adolescence].

PubMed

Buchmann, Arlette F; Blomeyer, Dorothea; Laucht, Manfred

2012-01-01

Suicidal behaviors are prevalent among young people. Numerous risk factors have been implicated in their development. In the framework of the longitudinal Mannheim Study of Children at Risk, 311 young adults (143 males, 168 females) aged 19-23 years were investigated in order 1) to determine the significance of different risk factors during development in predicting suicidal behaviors in young adulthood, 2) to identify potential risk factors discriminating between suicidal ideation and suicide attempts, and 3) to examine whether the effect of early risk factors was mediated by later occurring predictors. Young adults with suicidal behaviors displayed a number of abnormalities during development, including high load of early family adversity, suicidal ideation and psychiatric problems in childhood and adolescence, as well as low self esteem, poor school functioning, higher levels of novelty seeking, and enhanced affiliations with deviant peers in adolescence. Independent contributions to predicting suicidal behaviors in young adults were provided by early family adversity, suicidal ideation during childhood and adolescence, and low self esteem (with regard to suicidal ideation) and novelty seeking (with regard to suicide attempt), respectively. The impact of early adversity was mediated by child and adolescent externalizing disorders and low self esteem in adolescence. Possible implications of these findings for the prevention and treatment of suicidal behaviors are discussed.

Systems Toxicology: From Basic Research to Risk Assessment

PubMed Central

2014-01-01

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment. PMID:24446777

Systems toxicology: from basic research to risk assessment.

PubMed

Sturla, Shana J; Boobis, Alan R; FitzGerald, Rex E; Hoeng, Julia; Kavlock, Robert J; Schirmer, Kristin; Whelan, Maurice; Wilks, Martin F; Peitsch, Manuel C

2014-03-17

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment.

The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

PubMed

Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

2008-05-01

Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome.

A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

PubMed

St Pierre, Cristina; Guo, Jane; Shin, John D; Engstrom, Laura W; Lee, Hyun-Hee; Herbert, Alan; Surdi, Laura; Baker, James; Salmon, Michael; Shah, Sanjiv; Ellis, J Michael; Houshyar, Hani; Crackower, Michael A; Kleinschek, Melanie A; Jones, Dallas C; Hicks, Alexandra; Zaller, Dennis M; Alves, Stephen E; Ramadas, Ravisankar A

2017-01-01

While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

PubMed

Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

2016-02-01

To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Childhood adversities and post-traumatic stress disorder: evidence for stress sensitisation in the World Mental Health Surveys.

PubMed

McLaughlin, Katie A; Koenen, Karestan C; Bromet, Evelyn J; Karam, Elie G; Liu, Howard; Petukhova, Maria; Ruscio, Ayelet Meron; Sampson, Nancy A; Stein, Dan J; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Borges, Guilherme; Demyttenaere, Koen; Dinolova, Rumyana V; Ferry, Finola; Florescu, Silvia; de Girolamo, Giovanni; Gureje, Oye; Kawakami, Norito; Lee, Sing; Navarro-Mateu, Fernando; Piazza, Marina; Pennell, Beth-Ellen; Posada-Villa, José; Ten Have, Margreet; Viana, Maria Carmen; Kessler, Ronald C

2017-11-01

Background Although childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age. Aims To examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage. Method Epidemiological data were analysed from the World Mental Health Surveys ( n = 27 017). Results Four childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR) = 1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity-PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood. Conclusions Childhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences. © The Royal College of Psychiatrists 2017.

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression.

EPA Science Inventory

Building predictive gene signatures through simultaneous assessment of transcription factor activation and gene expression Exposure to many drugs and environmentally-relevant chemicals can cause adverse outcomes. These adverse outcomes, such as cancer, have been linked to mol...

Deviation from a preoperative surgical and anaesthetic care plan is associated with increased risk of adverse intraoperative events in major abdominal surgery.

PubMed

Gauss, T; Merckx, P; Brasher, C; Kavafyan, J; Le Bihan, E; Aussilhou, B; Belghiti, J; Mantz, J

2013-02-01

Perioperative coordination facilitates team communication and planning. The aim of this study was to determine how often deviation from predicted surgical conditions and a pre-established anaesthetic care plan in major abdominal surgery occurred, and whether this was associated with an increase in adverse clinical events. In this prospective observational study, weekly preoperative interdisciplinary team meetings were conducted according to a joint care plan checklist in a tertiary care centre in France. Any discordance with preoperative predictions and deviation from the care plan were noted. A link to the incidence of predetermined adverse intraoperative events was investigated. Intraoperative adverse clinical events (ACEs) occurred in 15 % of all cases and were associated with postoperative complications [relative risk (RR) = 1.5; 95 % confidence interval (1.1; 2.2)]. Quality of prediction of surgical procedural items was modest, with one in five to six items not correctly predicted. Discordant surgical prediction was associated with an increased incidence of ACE. Deviation from the anaesthetic care plan occurred in around 13 %, which was more frequent when surgical prediction was inaccurate (RR > 3) and independently associated with ACE (odds ratio 6). Surgery was more difficult than expected in up to one out of five cases. In a similar proportion, disagreement between preoperative care plans and observed clinical management was independently associated with an increased risk of adverse clinical events.

Early cumulative risk predicts externalizing behavior at age 10: The mediating role of adverse parenting.

PubMed

Gach, Emily J; Ip, Ka I; Sameroff, Arnold J; Olson, Sheryl L

2018-02-01

Multiple environmental risk factors in early childhood predict a broad range of adverse developmental outcomes. However, most prior longitudinal research has not illuminated explanatory mechanisms. Our main goals were to examine predictive associations between cumulative ecological risk factors in early childhood and children's later externalizing problems and to determine whether these associations were explained by variations in parenting quality. Participants were 241 children (118 girls) at risk for school-age conduct problems and their parents and teachers. Children were approximately 3 years old at Time 1 (T1) and 10 years old at Time 2 (T2). Reports of contextual risk at T1 were used to develop a cumulative risk index consisting of 6 singular risk variables from 3 ecological levels: social resources (low income; social isolation), family resources (marital aggression; poor total family functioning), and maternal resources (single parent status; poor maternal mental health). At T1, parenting variables were measured (corporal punishment, warm responsiveness, maternal efficacy, and negative perceptions of child behavior). At T2, mothers, fathers, and teachers reported child externalizing problems. Johnson's relative weight analysis revealed that the cumulative risk index was a more powerful predictor of age 10 years externalizing behavior than any of the singular contextual risk variables. Adverse parenting mediated the effects of cumulative risk on later child externalizing problems. Our findings have significant implications for understanding long-term effects of multiple contextual risk factors present in early childhood and for the implementation of positive parenting interventions early on. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Plasma bilirubin values on admission and ventricular remodeling after a first anterior ST-segment elevation acute myocardial infarction.

PubMed

Miranda, Berta; Barrabés, José A; Figueras, Jaume; Pineda, Victor; Rodríguez-Palomares, José; Lidón, Rosa-Maria; Sambola, Antonia; Bañeras, Jordi; Otaegui, Imanol; García-Dorado, David

2016-01-01

Bilirubin may elicit cardiovascular protection and heme oxygenase-1 overexpression attenuated post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and post-infarction remodeling is unknown. In 145 patients with a first anterior ST-segment elevation acute myocardial infarction (STEMI), we assessed whether plasma bilirubin on admission predicted adverse remodeling (left ventricular end-diastolic volume [LVEDV] increase ≥20% between discharge and 6 months, estimated by magnetic resonance imaging). Patients' baseline characteristics and management were comparable among bilirubin tertiles. LVEDV increased at 6 months (P < 0.001) with respect to the initial exam, but the magnitude of this increase was similar across increasing bilirubin tertiles (10.8 [30.2], 10.1 [22.9], and 12.7 [24.3]%, P = 0.500). Median (25-75 percentile) bilirubin values in patients with and without adverse remodeling were 0.75 (0.60-0.93) and 0.73 (0.60-0.92) mg/dL (P = 0.693). Absence of final TIMI flow grade 3 (odds ratio 3.92, 95% CI 1.12-13.66) and a history of hypertension (2.04, 0.93-4.50), but not admission bilirubin, were independently associated with adverse remodeling. Bilirubin also did not predict the increase in ejection fraction at 6 months. Admission bilirubin values are not related to LVEDV or ejection fraction progression after a first anterior STEMI and do not predict adverse ventricular remodeling. Key messages Bilirubin levels are inversely related to cardiovascular disease, and overexpression of heme oxygenase-1 (the enzyme that determines bilirubin production) has prevented post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and the progression of ventricular volumes and function in patients with acute myocardial infarction remained unexplored. In this cohort of patients with a first acute anterior ST-segment elevation myocardial infarction receiving contemporary management, bilirubin levels on admission were not predictive of the changes in left ventricular volumes or ejection fraction at 6 months measured by serial cardiac magnetic resonance imaging. The data are contrary to a significant protective effect of bilirubin against post-infarction ventricular remodeling.

Data-driven prediction of adverse drug reactions induced by drug drug interactions

DTIC Science & Technology

2017-06-08

currently on the market and for which drug-protein interaction information is available . These predictions are publicly accessible at http://avoid...associated with these ADRs via DDIs. We made the predictions publicly available via internet access. Keywords: Drug-drug interactions, Adverse drug reactions...ˆDeceased Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research

Adverse Effects of Cannabis on Adolescent Brain Development: A Longitudinal Study

PubMed Central

Camchong, Jazmin; Lim, Kelvin O; Kumra, Sanjiv

2017-01-01

Abstract Cannabis is widely perceived as a safe recreational drug and its use is increasing in youth. It is important to understand the implications of cannabis use during childhood and adolescence on brain development. This is the first longitudinal study that compared resting functional connectivity of frontally mediated networks between 43 healthy controls (HCs; 20 females; age M = 16.5 ± 2.7) and 22 treatment-seeking adolescents with cannabis use disorder (CUD; 8 females; age M = 17.6 ± 2.4). Increases in resting functional connectivity between caudal anterior cingulate cortex (ACC) and superior frontal gyrus across time were found in HC, but not in CUD. CUD showed a decrease in functional connectivity between caudal ACC and dorsolateral and orbitofrontal cortices across time. Lower functional connectivity between caudal ACC cortex and orbitofrontal cortex at baseline predicted higher amounts of cannabis use during the following 18 months. Finally, high amounts of cannabis use during the 18-month interval predicted lower intelligence quotient and slower cognitive function measured at follow-up. These data provide compelling longitudinal evidence suggesting that repeated exposure to cannabis during adolescence may have detrimental effects on brain resting functional connectivity, intelligence, and cognitive function. PMID:26912785

Obesity and unhealthy lifestyle associated with poor executive function among Malaysian adolescents.

PubMed

Tee, Joyce Ying Hui; Gan, Wan Ying; Tan, Kit-Aun; Chin, Yit Siew

2018-01-01

The understanding on the roles of obesity and lifestyle behaviors in predicting executive function of adolescents has been limited. Low executive function proficiency may have adverse effects on adolescents' school academic performance. This cross-sectional study aimed to examine the relationship between BMI-for-age and multiple lifestyle behaviors (operationalized as meal consumption, physical activity, and sleep quality) with executive function (operationalized as inhibition, working memory, and cognitive flexibility) on a sample of Malaysian adolescents aged between 12 and 16 years (N = 513). Participants were recruited from two randomly selected schools in the state of Selangor in Malaysia. Using a self-administered questionnaire, parent participants provided information concerning their sociodemographic data, whereas adolescent participants provided information regarding their meal consumptions, physical activity, and sleep quality. The modified Harvard step test was used to assess adolescents' aerobic fitness, while Stroop color-word, digit span, and trail-making tests were used to assess adolescents' inhibition, working memory, and cognitive flexibility, respectively. Three separate hierarchical regression analyses were conducted for each outcome namely, inhibition, working memory, and cognitive flexibility. After adjusted for sociodemographic factors and BMI-for-age, differential predictors of inhibition and working memory were found. Habitual sleep efficiency significantly and positively predicted inhibition. Regular dinner intakes, physical activity levels, and sleep quality significantly and positively predicted working memory. Household income emerged as a consistent predictor for all executive function domains. In conclusion, an increased trend of obesity and unhealthy lifestyles among adolescents were found to be associated with poorer executive function. Regular dinner intakes, higher physical activity levels and better sleep quality predicted better executive function despite the inverse relationship between obesity and executive function. Future studies may explore how lifestyle modifications can optimize the development of executive function in adolescents as well as relieve the burden of obesity.

Mothers’ Employment and Health of Low-Income Children

PubMed Central

Gennetian, Lisa; Hill, Heather; Lopoo, Leonard; London, Andrew

2010-01-01

This study examines whether maternal employment affects the health status of low-income, elementary-school-aged children using instrumental variables estimation and experimental data from a welfare-to-work program implemented in the early 1990s. Mother’s report of child health status is predicted as a function of exogenous variation in maternal employment associated with random assignment to the program group. IV estimates show a modest adverse effect of maternal employment on children’s health. Making use of data from another welfare-to-work program we propose that any adverse effect on child health may be tempered by increased family income and access to public health insurance coverage, findings with direct relevance to a number of current policy discussions. In a secondary analysis using fixed effects techniques on longitudinal survey data collected in 1998 and 2001, we find a comparable adverse effect of maternal employment on child health that supports the external validity of our primary result. PMID:20356641

Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.

PubMed

Lomanowska, A M; Boivin, M; Hertzman, C; Fleming, A S

2017-02-07

The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort.

PubMed

Bolliger, Daniel; Filipovic, Miodrag; Matt, Peter; Tanaka, Kenichi A; Gregor, Michael; Zenklusen, Urs; Seeberger, Manfred D; Lurati Buse, Giovanna

2016-01-01

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects

PubMed Central

Cronin, Mark T.D.; Enoch, Steven J.; Mellor, Claire L.; Przybylak, Katarzyna R.; Richarz, Andrea-Nicole; Madden, Judith C.

2017-01-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given. PMID:28744348

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects.

PubMed

Cronin, Mark T D; Enoch, Steven J; Mellor, Claire L; Przybylak, Katarzyna R; Richarz, Andrea-Nicole; Madden, Judith C

2017-07-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.

Daily Associations Among Self-control, Heavy Episodic Drinking, and Relationship Functioning: An Examination of Actor and Partner Effects

PubMed Central

Crane, Cory A.; Testa, Maria; Derrick, Jaye L.; Leonard, Kenneth E.

2014-01-01

An emerging literature suggests that temporary deficits in the ability to inhibit impulsive urges may be proximally associated with intimate partner aggression. The current study examined the experience of alcohol use and the depletion of self-control in the prediction of relationship functioning. Daily diary data collected from 118 heterosexual couples were analyzed using parallel multi-level Actor Partner Interdependence Models to assess the effects of heavy episodic drinking and depletion of self-control across partners on outcomes of participant-reported daily arguing with and anger toward an intimate partner. Heavy episodic drinking among actors predicted greater arguing but failed to interact with either actor or partner depletion. We also found that greater arguing was reported on days of high congruent actor and partner depletion. Both actor and partner depletion, as well as their interaction, predicted greater partner-specific anger. Greater partner-specific anger was generally reported on days of congruent actor and partner depletion, particularly on days of high partner depletion. The current results highlight the importance of independently assessing partner effects (i.e., depletion of self-control), which interact dynamically with disinhibiting actor effects, in the prediction of daily adverse relationship functioning. Results offer further support for the development of prospective individualized and couples-based interventions for partner conflict. PMID:24700558

The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression.

PubMed

Tunnard, Catherine; Rane, Lena J; Wooderson, Sarah C; Markopoulou, Kalypso; Poon, Lucia; Fekadu, Abebaw; Juruena, Mario; Cleare, Anthony J

2014-01-01

Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

Studying Biology to Understand Risk: Dosimetry Models and Quantitative Adverse Outcome Pathways

EPA Science Inventory

Confidence in the quantitative prediction of risk is increased when the prediction is based to as great an extent as possible on the relevant biological factors that constitute the pathway from exposure to adverse outcome. With the first examples now over 40 years old, physiologi...

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

PubMed Central

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

PubMed

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach.

Prognostic significance of dilated inferior vena cava in advanced decompensated heart failure.

PubMed

Lee, Hsin-Fu; Hsu, Lung-An; Chang, Chi-Jen; Chan, Yi-Hsin; Wang, Chun-Li; Ho, Wan-Jing; Chu, Pao-Hsien

2014-10-01

Dilated inferior vena cava (IVC) is prevalent among patients with heart failure (HF), but whether its presence predicts worsening renal function (WRF) or adverse outcomes is unclear. This cohort study analyzed patients with left ventricular ejection fraction <40 % and repeated hospitalizations (≥2 times) for HF between August 2009 and August 2011. The study endpoints were death and HF re-hospitalization. Among baseline parameters, IVC diameter was the most powerful predictor for the development of WRF (area under the curve = 0.795, cut-off value = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized for HF and 14 patients (19 %) died. The event rates were significantly greater in the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re-hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the risk of combined end-points was increased in patients with aging, elevated blood urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the development of WRF and could be a predictor for adverse outcomes.

Predictors of immune function in space flight

NASA Astrophysics Data System (ADS)

Shearer, William T.; Zhang, Shaojie; Reuben, James M.; Lee, Bang-Ning; Butel, Janet S.

2007-02-01

Of all of the environmental conditions of space flight that might have an adverse effect upon human immunity and the incidence of infection, space radiation stands out as the single-most important threat. As important as this would be on humans engaged in long and deep space flight, it obviously is not possible to plan Earth-bound radiation and infection studies in humans. Therefore, we propose to develop a murine model that could predict the adverse effects of space flight radiation and reactivation of latent virus infection for humans. Recent observations on the effects of gamma and latent virus infection demonstrate latent virus reactivation and loss of T cell mediated immune responses in a murine model. We conclude that using this small animal method of quantitating the amounts of radiation and latent virus infection and resulting alterations in immune responses, it may be possible to predict the degree of immunosuppression in interplanetary space travel for humans. Moreover, this model could be extended to include other space flight conditions, such as microgravity, sleep deprivation, and isolation, to obtain a more complete assessment of space flight risks for humans.

Identifying crash-prone traffic conditions under different weather on freeways.

PubMed

Xu, Chengcheng; Wang, Wei; Liu, Pan

2013-09-01

Understanding the relationships between traffic flow characteristics and crash risk under adverse weather conditions will help highway agencies develop proactive safety management strategies to improve traffic safety in adverse weather conditions. The primary objective is to develop separate crash risk prediction models for different weather conditions. The crash data, weather data, and traffic data used in this study were collected on the I-880N freeway in California in 2008 and 2010. This study considered three different weather conditions: clear weather, rainy weather, and reduced visibility weather. The preliminary analysis showed that there was some heterogeneity in the risk estimates for traffic flow characteristics by weather conditions, and that the crash risk prediction model for all weather conditions cannot capture the impacts of the traffic flow variables on crash risk under adverse weather conditions. The Bayesian random intercept logistic regression models were applied to link the likelihood of crash occurrence with various traffic flow characteristics under different weather conditions. The crash risk prediction models were compared to their corresponding logistic regression model. It was found that the random intercept model improved the goodness-of-fit of the crash risk prediction models. The model estimation results showed that the traffic flow characteristics contributing to crash risk were different across different weather conditions. The speed difference between upstream and downstream stations was found to be significant in each crash risk prediction model. Speed difference between upstream and downstream stations had the largest impact on crash risk in reduced visibility weather, followed by that in rainy weather. The ROC curves were further developed to evaluate the predictive performance of the crash risk prediction models under different weather conditions. The predictive performance of the crash risk model for clear weather was better than those of the crash risk models for adverse weather conditions. The research results could promote a better understanding of the impacts of traffic flow characteristics on crash risk under adverse weather conditions, which will help transportation professionals to develop better crash prevention strategies in adverse weather. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics.

PubMed

Bean, Judy A; Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Nierenberg, Kate; Reich, Andrew; Cheng, Yung Sung; Wanner, Adam; Benson, Janet; Naar, Jerome; Pierce, Richard; Abraham, William M; Kirkpatrick, Gary; Hollenbeck, Julie; Zaias, Julia; Mendes, Eliana; Baden, Daniel G

2011-09-01

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hip fractures are risky business: an analysis of the NSQIP data.

PubMed

Sathiyakumar, Vasanth; Greenberg, Sarah E; Molina, Cesar S; Thakore, Rachel V; Obremskey, William T; Sethi, Manish K

2015-04-01

Hip fractures are one of the most common types of orthopaedic injury with high rates of morbidity. Currently, no study has compared risk factors and adverse events following the different types of hip fracture surgeries. The purpose of this paper is to investigate the major and minor adverse events and risk factors for complication development associated with five common surgeries for the treatment of hip fractures using the NSQIP database. Using the ACS-NSQIP database, complications for five forms of hip surgeries were selected and categorized into major and minor adverse events. Demographics and clinical variables were collected and an unadjusted bivariate logistic regression analyses was performed to determine significant risk factors for adverse events. Five multivariate regressions were run for each surgery as well as a combined regression analysis. A total of 9640 patients undergoing surgery for hip fracture were identified with an adverse events rate of 25.2% (n=2433). Open reduction and internal fixation of a femoral neck fracture had the greatest percentage of all major events (16.6%) and total adverse events (27.4%), whereas partial hip hemiarthroplasty had the greatest percentage of all minor events (11.6%). Mortality was the most common major adverse event (44.9-50.6%). For minor complications, urinary tract infections were the most common minor adverse event (52.7-62.6%). Significant risk factors for development of any adverse event included age, BMI, gender, race, active smoking status, history of COPD, history of CHF, ASA score, dyspnoea, and functional status, with various combinations of these factors significantly affecting complication development for the individual surgeries. Hip fractures are associated with significantly high numbers of adverse events. The type of surgery affects the type of complications developed and also has an effect on what risk factors significantly predict the development of a complication. Concerted efforts from orthopaedists should be made to identify higher risk patients and prevent the most common adverse events that occur postoperatively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Computational Approaches for Identifying Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

Near Real-Time Optimal Prediction of Adverse Events in Aviation Data

NASA Technical Reports Server (NTRS)

Martin, Rodney Alexander; Das, Santanu

2010-01-01

The prediction of anomalies or adverse events is a challenging task, and there are a variety of methods which can be used to address the problem. In this paper, we demonstrate how to recast the anomaly prediction problem into a form whose solution is accessible as a level-crossing prediction problem. The level-crossing prediction problem has an elegant, optimal, yet untested solution under certain technical constraints, and only when the appropriate modeling assumptions are made. As such, we will thoroughly investigate the resilience of these modeling assumptions, and show how they affect final performance. Finally, the predictive capability of this method will be assessed by quantitative means, using both validation and test data containing anomalies or adverse events from real aviation data sets that have previously been identified as operationally significant by domain experts. It will be shown that the formulation proposed yields a lower false alarm rate on average than competing methods based on similarly advanced concepts, and a higher correct detection rate than a standard method based upon exceedances that is commonly used for prediction.

[Are non-clinical studies predictive of adverse events in humans?].

PubMed

Claude, N

2007-09-01

The predictibility of adverse events induced by drugs in non-clinical safety studies performed on in vitro and/or in vivo models is a key point for the safety of humans exposed to pharmaceuticals. The strength and the weakness of animal studies to predict human toxicity were assessed by an international study on the concordance of the toxicity of 150 pharmaceuticals observed in humans with that observed in experimental animals. The results showed a good correlation (70% of the adverse events in humans were detected in animal studies) and an early time to first appearance of concordant animal toxicity: 94% were first observed in studies of 1 month or less in duration. The highest incidence of overall concordance was seen in hematological and cardiovascular adverse effects and the least was seen in cutaneous and ophthalmological adverse effects. These studies, scientifically and regulatory standardized, need, in some cases to be adapted to specific problems linked to sensitive populations (young, old or with a pathology which could be worsened by the drug), or specific pharmaceuticals (produced by biotechnology). Some severe adverse events are not detected in conventional animal models (immuno-allergy, idiosyncrasy). Taken together, these elements support the value of toxicology studies to predict many human toxic events associated with pharmaceuticals. Nevertheless, a part of human toxicity is not detected by these experimental approaches, and new tools developed through progress in biology and bio-informatics should reduce this uncertainly margin.

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is freely accessible at http://idaapm.helsinki.fi and can be exploited through a KNIME workflow connected to the database.Graphical abstractFDA approved drug data integration for predictive modeling.

Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

PubMed

Allaf, M Baraa; Campbell, Winston A; Vintzileos, Anthony M; Haeri, Sina; Javadian, Pouya; Shamshirsaz, Amir A; Ogburn, Paul; Figueroa, Reinaldo; Wax, Joseph; Markenson, Glenn; Chavez, Martin R; Ravangard, Samadh F; Ruano, Rodrigo; Sangi-Haghpeykar, Haleh; Salmanian, Bahram; Meyer, Marjorie; Johnson, Jeffery; Ozhand, Ali; Davis, Sarah; Borgida, Adam; Belfort, Michael A; Shamshirsaz, Alireza A

2014-09-01

To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin-twin transfusion syndrome or adverse neonatal outcomes. In our cohort, only second-trimester abdominal circumference and estimated fetal weight discordances in monochorionic diamniotic twin pregnancies were predictive of adverse composite obstetric outcomes. Twin-twin transfusion syndrome and adverse neonatal outcomes were not predicted by any of the intertwin discordances measured. © 2014 by the American Institute of Ultrasound in Medicine.

Childhood physical abuse predicts stressor-evoked activity within central visceral control regions

PubMed Central

Sheu, Lei K.; Midei, Aimee J.; Gianaros, Peter J.

2015-01-01

Early life experience differentially shapes later stress reactivity, as evidenced by both animal and human studies. However, early experience-related changes in the function of central visceral neural circuits that control stress responses have not been well characterized, particularly in humans. The paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), amygdala (Amyg) and subgenual anterior cingulate cortex (sgACC) form a core visceral stress-responsive circuit. The goal of this study is to examine how childhood emotional and physical abuse relates to adulthood stressor-evoked activity within these visceral brain regions. To evoke acute states of mental stress, participants (n = 155) performed functional magnetic resonance imaging (fMRI)-adapted versions of the multi-source interference task (MSIT) and the Stroop task with simultaneous monitoring of mean arterial pressure (MAP) and heart rate. Regression analyses revealed that childhood physical abuse correlated positively with stressor-evoked changes in MAP, and negatively with unbiased, a priori extractions of fMRI blood-oxygen level-dependent signal change values within the sgACC, BNST, PVN and Amyg (n = 138). Abuse-related changes in the function of visceral neural circuits may reflect neurobiological vulnerability to adverse health outcomes conferred by early adversity. PMID:24847113

Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity ?

PubMed Central

Herskind, Carsten; Talbot, Christopher J.; Kerns, Sarah L.; Veldwijk, Marlon R.; Rosenstein, Barry S.; West, Catharine M. L.

2016-01-01

Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy. PMID:26944314

Severe adverse life events and depressive symptoms among women with, or at risk for, HIV infection in four cities in the United States of America.

PubMed

Moore, J; Schuman, P; Schoenbaum, E; Boland, B; Solomon, L; Smith, D

1999-12-03

To examine frequency and predictors of severe adverse life events and depressive symptoms among HIV-infected women and a comparison group of uninfected women. Analysis of baseline data collected from HIV-infected and uninfected women in a prospective cohort study of HIV infection and women, the HIV Epidemiologic Research Study. The sample of 871 HIV-infected and 439 demographically and behaviorally similar uninfected women were recruited from four metropolitan areas in the USA. Women provided interview information that included sociodemographic characteristics, sexual and drug-using behaviors, and social and psychological functioning. The outcome measures were number of severe adverse life events (e.g., insufficient money for necessities, physical attack or rape, death of a person close to them) and levels of depressive symptoms. HIV-infected and uninfected women reported numerous adverse life events and high levels of depressive symptoms. The two groups, however, did not differ on either outcome measure. Low socio-economic status, injecting drug and crack cocaine use, and high risk sexual activity were related to reports of more adverse events and depressive symptoms for both groups. HIV-infected and uninfected women in socially and economically disadvantaged environments experience many adverse events and high levels of depressive symptoms. HIV infection, at least during the early phase, may be less important than socio-environmental factors in predicting negative psychosocial outcomes for women.

Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence. The trails study.

PubMed

Laceulle, Odilia M; Nederhof, Esther; van Aken, Marcel A G; Ormel, Johan

2017-11-01

The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19. Adolescents who reported being exposed to social defeat showed increases in basal cortisol (ɳ 2 =0.029) and decreases in reaction to the stress task (ɳ 2 =0.030) from age 16-19, compared to their peers in the loss/illness and no stress group. The current study provides unique longitudinal data on the role of adversity in HPA-axis functioning. Evidence is provided that adversity can affect the body's neuroendocrine response to stress, dependent on the nature of both the HPA-measures and adverse events under study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events.

PubMed

Haas, David W; Bradford, Yuki; Verma, Anurag; Verma, Shefali S; Eron, Joseph J; Gulick, Roy M; Riddler, Sharon A; Sax, Paul E; Daar, Eric S; Morse, Gene D; Acosta, Edward P; Ritchie, Marylyn D

2018-05-29

We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10). Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics.

The Effects of Childhood and Adolescent Adversity on Substance Use Disorders and Poor Health in Early Adulthood

PubMed Central

Wolitzky-Taylor, Kate; Sewart, Amy; Vrshek-Schallhorn, Suzanne; Zinbarg, Richard; Mineka, Susan; Hammen, Constance; Bobova, Lyuba; Adam, Emma K.; Craske, Michelle G.

2016-01-01

Childhood and adolescent adversity have been shown to predict later mental and physical health outcomes. Understanding which aspects and developmental timings of adversity are important, and the mechanisms by which they have their impact may help guide intervention approaches. A large subset of adolescents (N = 457; Female 68.9%) from the 10-year longitudinal Youth Emotion Project was examined to better understand the associations among childhood/adolescent adversity, substance use disorder, and later health quality. Adolescent (but not childhood) adversities were associated with poorer health in late adolescence/early adulthood, adolescent adversities were associated with subsequent onset of substance use disorder, and adolescent adversities continued to be associated with poorer health in late adolescence/early adulthood after accounting for the variance explained by substance use disorder onset. These associations were observed after statistically accounting for emotional disorders and socioeconomic status. Specific domains of adversity uniquely predicted substance use disorder and poorer health outcomes. In contrast with current recent research, our findings suggest the association between childhood/adolescent adversity and poorer health outcomes in late adolescence and emerging adulthood are not entirely accounted for by substance use disorder, suggesting efforts to curtail family-based adolescent adversity may have downstream health benefits. PMID:27613006

The Effects of Childhood and Adolescent Adversity on Substance Use Disorders and Poor Health in Early Adulthood.

PubMed

Wolitzky-Taylor, Kate; Sewart, Amy; Vrshek-Schallhorn, Suzanne; Zinbarg, Richard; Mineka, Susan; Hammen, Constance; Bobova, Lyuba; Adam, Emma K; Craske, Michelle G

2017-01-01

Childhood and adolescent adversity have been shown to predict later mental and physical health outcomes. Understanding which aspects and developmental timings of adversity are important, and the mechanisms by which they have their impact may help guide intervention approaches. A large subset of adolescents (N = 457; Female 68.9 %) from the 10-year longitudinal Youth Emotion Project was examined to better understand the associations among childhood/adolescent adversity, substance use disorder, and later health quality. Adolescent (but not childhood) adversities were associated with poorer health in late adolescence/early adulthood, adolescent adversities were associated with subsequent onset of substance use disorder, and adolescent adversities continued to be associated with poorer health in late adolescence/early adulthood after accounting for the variance explained by substance use disorder onset. These associations were observed after statistically accounting for emotional disorders and socioeconomic status. Specific domains of adversity uniquely predicted substance use disorder and poorer health outcomes. In contrast with current recent research, our findings suggest the association between childhood/adolescent adversity and poorer health outcomes in late adolescence and emerging adulthood are not entirely accounted for by substance use disorder, suggesting efforts to curtail family-based adolescent adversity may have downstream health benefits.

Safety and efficacy of pirfenidone in severe Idiopathic Pulmonary Fibrosis: A real-world observational study.

PubMed

Tzouvelekis, Argyrios; Ntolios, Paschalis; Karampitsakos, Theodoros; Tzilas, Vasilios; Anevlavis, Stavros; Bouros, Evangelos; Steiropoulos, Paschalis; Koulouris, Nikolaos; Stratakos, Grigoris; Froudarakis, Marios; Bouros, Demosthenes

2017-10-01

Pirfenidone is a novel anti-fibrotic drug that has shown efficacy in five randomized multicenter clinical trials enrolling patients with Idiopathic Pulmonary Fibrosis of mild-to-moderate disease severity. Scarce data supports the use of pirfenidone in IPF patients with more advanced disease. To investigate the safety and efficacy profile of pirfenidone in IPF patients with severe lung function impairment. This was a retrospective study enrolling patients with advanced IPF (FVC%predicted < 50% and/or (DLco%predicted <35%) receiving pirfenidone for at least 6 months. Between September 2011 and March 2013, we identified 43 patients with severe IPF (baseline meanFVC%predicted±SD: 63.8 ± 20.3, meanDL CO %predicted: 27.3 ± 8.2), of mean age±SD: 66.3 + 9.7, 34 males (81%) that received pirfenidone (2.403 mg/daily) for one year. Pirfenidone treatment was associated with a trend towards decrease in functional decline compared to 6-months before treatment initiation but failed to show any benefit after one year of treatment (ΔFVC: -3.3 ± 4.6 vs 0.49 ± 11.4 and vs. -5.8 ± 11.8, p = 0.06 and p = 0.04, respectively and ΔDL CO : -13.3 ± 15.2 vs. -10.1 ± 16.6 and vs. 28.3 ± 19.2, p = 0.39 and p = 0.002, respectively). Gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%) were the most common adverse events. Adverse events led to treatment discontinuation in 9 patients (20.9%) and dose reduction in 14 (32.5%). Pirfenidone appears to be safe when administered in patients with advanced IPF. Pirfenidone efficacy in IPF patients with severe lung function impairment may diminish after 6 months of treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis with renal failure in a South Indian tertiary-care hospital.

PubMed

Prabhu, Mayoor V; S, Arun; Ramesh, Venkat

In the tropics, the triad of fever, thrombocytopenia, and AKI portends a grim prognosis with high mortality and a severe strain on already-stretched resources. Malaria, dengue, and leptospirosis account for most cases. We undertook a review of cases to determine factors accounting for adverse prognosis. All patients presenting to the emergency room (ER) with a history of fever, thrombocytopenia, and renal failure were included in the study. Patients were followed until discharge or death, and end points looked at were 1-week and 30-day mortality, and renal function upon discharge. Parameters like liver function test (LFT), renal function, and platelet count upon discharge were also documented. A total of 43 patients was included in the study. Mean age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were 23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000, serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical ventilation, oliguria on admission, and need for dialysis all were highly predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of > 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality. Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients with leptospirosis. Factors like low platelet count, oliguria, need for dialysis, high APACHE and SOFA scores on admission, need for mechanical ventilation, and low serum albumin portend a grave prognosis. There is need for randomized control trials (RCT) to further determine adverse prognostic factors in this subsect of patients.

Developing and applying adverse outcome pathways: What you need to know

EPA Science Inventory

Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology

EPA Science Inventory

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...

Using the Personal Background Preparation Survey to Identify Health Science Professions Students at Risk for Adverse Academic Events

ERIC Educational Resources Information Center

Johnson, Craig W.; Johnson, Ronald; McKee, John C.; Kim, Mira

2009-01-01

In the first predictive validity study of a diagnostic and prescriptive instrument for averting adverse academic status events (AASE) among multiple populations of diverse health science professions students, entering matriculates' personal background and preparation survey (PBPS) scores consistently significantly predicted 1st- or 2nd-year AASE.…

Childhood adversity and behavioral health outcomes for youth: An investigation using state administrative data.

PubMed

Lucenko, Barbara A; Sharkova, Irina V; Huber, Alice; Jemelka, Ron; Mancuso, David

2015-09-01

This study aimed to measure the relative contribution of adverse experiences to adolescent behavioral health problems using administrative data. Specifically, we sought to understand the predictive value of adverse experiences on the presence of mental health and substance abuse problems for youth receiving publicly funded social and health services. Medicaid claims and other service records were analyzed for 125,123 youth age 12-17 and their biological parents. Measures from administrative records reflected presence of parental domestic violence, mental illness, substance abuse, criminal justice involvement, child abuse and/or neglect, homelessness, and death of a biological parent. Mental health and substance abuse status of adolescents were analyzed as functions of adverse experiences and other youth characteristics using logistic regression. In multivariate analyses, all predictors except parental domestic violence were statistically significant for substance abuse; parental death, parental mental illness, child abuse or neglect and homelessness were statistically significant for mental illness. Odds ratios for child abuse/neglect were particularly high in both models. The ability to identify risks during childhood using administrative data suggests the potential to target prevention and early intervention efforts for children with specific family risk factors who are at increased risk for developing behavioral health problems during adolescence. This study illustrates the utility of administrative data in understanding adverse experiences on children and the advantages and disadvantages of this approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Childhood adversity and midlife suicidal ideation.

PubMed

Stansfeld, S A; Clark, C; Smuk, M; Power, C; Davidson, T; Rodgers, B

2017-01-01

Childhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties. At 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood. Illness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67-6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29-5.75), sexual abuse (OR 4.99, 95% CI 2.90-11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI -7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97-27.88) and sexual abuse (OR 6.59, 95% CI 2.40-38.36) with suicidal ideation at 45 years. Adversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive interventions.

Childhood maltreatment is associated with a sex-dependent functional reorganization of a brain inhibitory control network.

PubMed

Elton, Amanda; Tripathi, Shanti P; Mletzko, Tanja; Young, Jonathan; Cisler, Josh M; James, G Andrew; Kilts, Clinton D

2014-04-01

Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However, the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 females) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor. Copyright © 2013 Wiley Periodicals, Inc.

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse Effects of Cannabis on Adolescent Brain Development: A Longitudinal Study.

PubMed

Camchong, Jazmin; Lim, Kelvin O; Kumra, Sanjiv

2017-03-01

Cannabis is widely perceived as a safe recreational drug and its use is increasing in youth. It is important to understand the implications of cannabis use during childhood and adolescence on brain development. This is the first longitudinal study that compared resting functional connectivity of frontally mediated networks between 43 healthy controls (HCs; 20 females; age M = 16.5 ± 2.7) and 22 treatment-seeking adolescents with cannabis use disorder (CUD; 8 females; age M = 17.6 ± 2.4). Increases in resting functional connectivity between caudal anterior cingulate cortex (ACC) and superior frontal gyrus across time were found in HC, but not in CUD. CUD showed a decrease in functional connectivity between caudal ACC and dorsolateral and orbitofrontal cortices across time. Lower functional connectivity between caudal ACC cortex and orbitofrontal cortex at baseline predicted higher amounts of cannabis use during the following 18 months. Finally, high amounts of cannabis use during the 18-month interval predicted lower intelligence quotient and slower cognitive function measured at follow-up. These data provide compelling longitudinal evidence suggesting that repeated exposure to cannabis during adolescence may have detrimental effects on brain resting functional connectivity, intelligence, and cognitive function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Resilience linked to personality dimensions, alexithymia and affective symptoms in motor functional neurological disorders.

PubMed

Jalilianhasanpour, Rozita; Williams, Benjamin; Gilman, Isabelle; Burke, Matthew J; Glass, Sean; Fricchione, Gregory L; Keshavan, Matcheri S; LaFrance, W Curt; Perez, David L

2018-04-01

Reduced resilience, a construct associated with maladaptive stress coping and a predisposing vulnerability for Functional Neurological Disorders (FND), has been under-studied compared to other neuropsychiatric factors in FND. This prospective case-control study investigated self-reported resilience in patients with FND compared to controls and examined relationships between resilience and affective symptoms, personality traits, alexithymia, health status and adverse life event burden. 50 individuals with motor FND and 47 healthy controls participated. A univariate test followed by a logistic regression analysis investigated group-level differences in Connor-Davidson Resilience Scale (CD-RISC) scores. For within-group analyses performed separately in patients with FND and controls, univariate screening tests followed by multivariate linear regression analyses examined factors associated with self-reported resilience. Adjusting for age, gender, education status, ethnicity and lifetime adverse event burden, patients with FND reported reduced resilience compared to controls. Within-group analyses in patients with FND showed that individual-differences in mental health, extraversion, conscientiousness, and openness positively correlated with CD-RISC scores; post-traumatic stress disorder symptom severity, depression, anxiety, alexithymia and neuroticism scores negatively correlated with CD-RISC scores. Extraversion independently predicted resilience scores in patients with FND. In control subjects, univariate associations were appreciated between CD-RISC scores and gender, personality traits, anxiety, alexithymia and physical health; conscientiousness independently predicted resilience in controls. Patients with FND reported reduced resilience, and CD-RISC scores covaried with other important predisposing vulnerabilities for the development of FND. Future research should investigate if the CD-RISC is predictive of clinical outcomes in patients with FND. Copyright © 2018 Elsevier Inc. All rights reserved.

The Impact of Adverse Child and Adult Experiences on Recovery from Serious Mental Illness

PubMed Central

Stumbo, Scott P.; Yarborough, Bobbi Jo H.; Paulson, Robert I.; Green, Carla A.

2015-01-01

Objective To compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. Methods As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a two-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Results Child and adult exposures to adverse experiences were high, at 91% and 82% respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning, social functioning, and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Conclusions and Implications for Practice Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. PMID:26053533

Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

ERIC Educational Resources Information Center

Kiff, Cara J.; Cortes, Rebecca C.; Lengua, Liliana J.; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

2012-01-01

Exposure to adversity during childhood and adolescence predicts adjustment across development. Furthermore, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal…

Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

PubMed

Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

2011-08-01

Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

PubMed

Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

2013-01-01

The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

PubMed Central

Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

2015-01-01

Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

PubMed

Kim, M H; Lin, J; Hussein, M; Battleman, D

2009-12-01

Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

NASA Technical Reports Server (NTRS)

Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2011-01-01

Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.

PubMed

Page, Rachael; Ferraro, Zachary Michael; Moretti, Felipe; Fung, Karen Fung Kee

2014-01-01

The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. A quasi-systematic review was conducted in PubMed and Ovid using the key terms "gastroschisis," "predictors," "outcome," and "ultrasound." A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD.

Adversity in childhood linked to elevated striatal dopamine function in adulthood.

PubMed

Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

2016-10-01

Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Do race, neglect, and childhood poverty predict physical health in adulthood? A multilevel prospective analysis

PubMed Central

Nikulina, Valentina

2015-01-01

Childhood neglect and poverty often co-occur and both have been linked to poor physical health outcomes. In addition, Blacks have higher rates of childhood poverty and tend to have worse health than Whites. This paper examines the unique and interacting effects of childhood neglect, race, and family and neighborhood poverty on adult physical health outcomes. This prospective cohort design study uses a sample (N = 675) of court-substantiated cases of childhood neglect and matched controls followed into adulthood (Mage = 41). Health indicators (C-Reactive Protein [CRP], hypertension, and pulmonary functioning) were assessed through blood collection and measurements by a registered nurse. Data were analyzed using hierarchical linear models to control for clustering of participants in childhood neighborhoods. Main effects showed that growing up Black predicted CRP and hypertension elevations, despite controlling for neglect and childhood family and neighborhood poverty and their interactions. Multivariate results showed that race and childhood adversities interacted to predict adult health outcomes. Childhood family poverty predicted increased risk for hypertension for Blacks, not Whites. In contrast, among Whites, childhood neglect predicted elevated CRP. Childhood neighborhood poverty interacted with childhood family poverty to predict pulmonary functioning in adulthood. Gender differences in health indicators were also observed. The effects of childhood neglect, childhood poverty, and growing up Black in the United States are manifest in physical health outcomes assessed 30 years later. Implications are discussed. PMID:24189205

Correlates of adverse childhood events among adults with schizophrenia spectrum disorders.

PubMed

Rosenberg, Stanley D; Lu, Weili; Mueser, Kim T; Jankowski, Mary Kay; Cournos, Francine

2007-02-01

Multiple studies have found that childhood adversity is related to a range of poor mental health, substance abuse, poor physical health, and poor social functioning outcomes in the general population of adults. However, despite the high rates of childhood adversity in schizophrenia, the clinical correlates of these events have not been systematically evaluated. This study evaluated the relationship between adverse experiences in childhood and functional, clinical, and health outcomes among adults with schizophrenia. The authors surveyed 569 adults with schizophrenia regarding adverse childhood events (including physical abuse, sexual abuse, parental mental illnesses, loss of a parent, parental separation or divorce, witnessing domestic violence, and foster or kinship care). The relationships between cumulative exposure to these events and psychiatric, physical, and functional outcomes were evaluated. Increased exposure to adverse childhood events was strongly related to psychiatric problems (suicidal thinking, hospitalizations, distress, and posttraumatic stress disorder), substance abuse, physical health problems (HIV infection), medical service utilization (physician visits), and poor social functioning (homelessness or criminal justice involvement). The findings extend the results of research in the general population by suggesting that childhood adversity contributes to worse mental health, substance abuse, worse physical health, and poor functional outcomes in schizophrenia.

Predicting Occurrence of Spine Surgery Complications Using "Big Data" Modeling of an Administrative Claims Database.

PubMed

Ratliff, John K; Balise, Ray; Veeravagu, Anand; Cole, Tyler S; Cheng, Ivan; Olshen, Richard A; Tian, Lu

2016-05-18

Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery. We used longitudinal prospective data from a national claims database and developed a predictive model incorporating complication type and frequency of occurrence following spine surgery procedures. We structured our model to assess the impact of features such as preoperative diagnosis, patient comorbidities, location in the spine, anterior versus posterior approach, whether fusion had been performed, whether instrumentation had been used, number of levels, and use of bone morphogenetic protein (BMP). We assessed a variety of adverse events. Prediction models were built using logistic regression with additive main effects and logistic regression with main effects as well as all 2 and 3-factor interactions. Least absolute shrinkage and selection operator (LASSO) regularization was used to select features. Competing approaches included boosted additive trees and the classification and regression trees (CART) algorithm. The final prediction performance was evaluated by estimating the area under a receiver operating characteristic curve (AUC) as predictions were applied to independent validation data and compared with the Charlson comorbidity score. The model was developed from 279,135 records of patients with a minimum duration of follow-up of 30 days. Preliminary assessment showed an adverse-event rate of 13.95%, well within norms reported in the literature. We used the first 80% of the records for training (to predict adverse events) and the remaining 20% of the records for validation. There was remarkable similarity among methods, with an AUC of 0.70 for predicting the occurrence of adverse events. The AUC using the Charlson comorbidity score was 0.61. The described model was more accurate than Charlson scoring (p < 0.01). We present a modeling effort based on administrative claims data that predicts the occurrence of complications after spine surgery. We believe that the development of a predictive modeling tool illustrating the risk of complication occurrence after spine surgery will aid in patient counseling and improve the accuracy of risk modeling strategies. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Perinatal Factors Affecting Expression of Obsessive Compulsive Disorder in Children and Adolescents

PubMed Central

Wieland, Natalie; Carey, Kathleen; Vivas, Fé; Petty, Carter R.; Johnson, Jessica; Reichert, Elizabeth; Pauls, David; Biederman, Joseph

2008-01-01

Abstract Objective To examine whether adverse perinatal experiences of children are associated with obsessive compulsive disorder (OCD) in youth. Methods Subjects were 130 children and adolescents with OCD recruited from a family genetic study of pediatric OCD and 49 matched controls from a contemporaneous family case-control study of attention-deficit/hyperactivity disorder (ADHD). Subjects were comprehensively assessed in multiple domains of function. A systematic history of pregnancy, delivery, and infancy complications was obtained. Results Compared to normal controls, children with OCD had mothers with significantly higher rates of illness during pregnancy requiring medical care (χ2 = 8.61, p = 0.003) and more birth difficulties (induced labor, forceps delivery, nuchal cord, or prolonged labor) (χ2 = 7.51, p = 0.006). Among the OCD-affected children, we found several significant associations between adverse perinatal experiences and earlier age at onset, increased OCD severity, and increased risk for comorbid ADHD, chronic tic disorder, anxiety disorder, and major depressive disorder. Conclusion Although exploratory, our analyses found that children with OCD had higher rates of several adverse perinatal experiences compared with controls. Among OCD-affected children, comorbid psychopathology was predicted by specific perinatal risk factors. Prospective studies of perinatal adverse events that minimize potential recall bias and type I errors are needed. PMID:18759647

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

PubMed

Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

2017-05-01

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

The impact of allostatic load on maternal sympathovagal functioning in stressful child contexts: Implications for problematic parenting

PubMed Central

STURGE-APPLE, MELISSA L.; SKIBO, MICHAEL A.; ROGOSCH, FRED A.; IGNJATOVIC, ZELJKO; HEINZELMAN, WENDI

2011-01-01

The present study applies an allostatic load framework to an examination of the relationship between maternal psychosocial risk factors and maladaptive parenting behaviors. Specifically, the implications of low socioeconomic status and maternal depressive symptoms for maternal sympathovagal functioning during young children’s distress were examined, as well as whether that functioning was, in turn, associated with maternal insensitivity, hostility, intrusiveness, and disengagement during mother–child dyadic interaction. Consistent with an allostatic framework, three patterns of sympathovagal functioning were expected to emerge: normative arousal, hyperarousal, and hypoarousal profiles. Furthermore, meaningful associations between maternal psychosocial risk factors, maladaptive parenting behaviors, and the three profiles of sympathovagal functioning were anticipated. Participants included 153 mother–toddler dyads recruited proportionately from lower and middle socioeconomic status backgrounds. Mothers’ sympathovagal response to their child’s distress was assessed during the Strange Situation paradigm, and mothers’ parenting behavior was assessed during a dyadic free-play interaction. As hypothesized, normative arousal, hyperarousal, and hypoarousal profiles of maternal sympathovagal functioning were identified. Maternal depressive symptomatology predicted the hyperarousal profile, whereas socioeconomic adversity predicted hypoarousal. Moreover, allostatic load profiles were differentially associated with problematic parenting behaviors. These findings underscore the role of physiological dysregulation as a mechanism in the relationship between proximal risk factors and actual maladaptive parenting behaviors. PMID:21756435

The impact of adverse child and adult experiences on recovery from serious mental illness.

PubMed

Stumbo, Scott P; Yarborough, Bobbi Jo H; Paulson, Robert I; Green, Carla A

2015-12-01

The purpose of this study was to compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a 2-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia, or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Child and adult exposures to adverse experiences were high, at 91% and 82%, respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning and social functioning and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. (c) 2015 APA, all rights reserved).

Structure provided by parents in middle childhood predicts cortisol reactivity in adolescence among the offspring of parents with bipolar disorder and controls.

PubMed

Ellenbogen, Mark A; Hodgins, Sheilagh

2009-06-01

Recent studies suggest that childhood exposure to adversity influences later functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Parenting style in childhood, a putative moderator of adversity, may be important in determining HPA reactivity in adolescence. As part of a prospective, longitudinal study, saliva was collected at awakening and 30 and 60 min later over 2 days among 27 offspring of parents with bipolar disorder (high risk; 16.7+/-1.5 years) and 26 offspring of parents with no mental disorders (low risk; 16.2+/-1.7 years). In addition, 24 of the high risk and 22 of the low risk adolescents completed the "Trier Social Stress Test" (TSST). Parents had rated their parenting style when their offspring were 6-13 years of age. Low levels of structure (i.e. organization and consistency) provided by parents in middle childhood were predictive of an elevated cortisol response following awakening (beta=-0.36; p<0.05) and during the TSST (beta=-0.33; p<0.05), even while controlling for risk group. These associations were independent of other indices of environmental risk, and of adolescents' mood and behavior. The level of structure provided by parents in childhood predicted independent measures of cortisol reactivity in adolescence, suggesting that parenting style may regulate different aspects of HPA reactivity.

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

PubMed Central

Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

2016-01-01

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

PubMed

Puterman, Eli; Gemmill, Alison; Karasek, Deborah; Weir, David; Adler, Nancy E; Prather, Aric A; Epel, Elissa S

2016-10-18

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Cumulative stress and autonomic dysregulation in a community sample.

PubMed

Lampert, Rachel; Tuit, Keri; Hong, Kwang-Ik; Donovan, Theresa; Lee, Forrester; Sinha, Rajita

2016-05-01

Whether cumulative stress, including both chronic stress and adverse life events, is associated with decreased heart rate variability (HRV), a non-invasive measure of autonomic status which predicts poor cardiovascular outcomes, is unknown. Healthy community dwelling volunteers (N = 157, mean age 29 years) participated in the Cumulative Stress/Adversity Interview (CAI), a 140-item event interview measuring cumulative adversity including major life events, life trauma, recent life events and chronic stressors, and underwent 24-h ambulatory ECG monitoring. HRV was analyzed in the frequency domain and standard deviation of NN intervals (SDNN) calculated. Initial simple regression analyses revealed that total cumulative stress score, chronic stressors and cumulative adverse life events (CALE) were all inversely associated with ultra low-frequency (ULF), very low-frequency (VLF) and low-frequency (LF) power and SDNN (all p < 0.05). In hierarchical regression analyses, total cumulative stress and chronic stress each was significantly associated with SDNN and ULF even after the highly significant contributions of age and sex, with no other covariates accounting for additional appreciable variance. For VLF and LF, both total cumulative stress and chronic stress significantly contributed to the variance alone but were not longer significant after adjusting for race and health behaviors. In summary, total cumulative stress, and its components of adverse life events and chronic stress were associated with decreased cardiac autonomic function as measured by HRV. Findings suggest one potential mechanism by which stress may exert adverse effects on mortality in healthy individuals. Primary preventive strategies including stress management may prove beneficial.

Cumulative stress and autonomic dysregulation in a community sample

PubMed Central

Lampert, Rachel; Tuit, Keri; Hong, Kwang-ik; Donovan, Theresa; Lee, Forrester; Sinha, Rajita

2016-01-01

Whether cumulative stress, including both chronic stress and adverse life events, is associated with decreased heart rate variability (HRV), a non-invasive measure of autonomic status which predicts poor cardiovascular outcomes, is unknown. Healthy community dwelling volunteers, (N= 157, mean age 29 years) participated in the Cumulative Stress/Adversity Interview, (CAI) a 140-item event interview measuring cumulative adversity including major life events, life trauma, recent life events and chronic stressors, and underwent 24 hour ambulatory ECG monitoring. HRV was analyzed in the frequency domain and standard deviation of NN intervals (SDNN) calculated. Initial simple regression analyses revealed that total cumulative stress score, chronic stressors, and cumulative adverse life events (CALE) were all inversely associated with ultra low frequency (ULF), very low frequency (VLF), and low frequency (LF) power and SDNN (all p<0.05). In hierarchical regression analyses, total cumulative stress and chronic stress each was significantly associated with SDNN and ULF even after the high significant contribution of age and sex, with no other covariates accounting for additional appreciable variance. For VLF and LF, both total cumulative stress and chronic stress significantly contributed to the variance were no longer significant after adjusting for race and health behaviors. (p’s<.05). In summary, total cumulative stress, and its components of adverse life events and chronic stress were associated with decreased cardiac autonomic function as measured by HRV. Findings suggest one potential mechanism by which stress may exert adverse effects on mortality in healthy individuals. Primary preventive strategies including stress management may prove beneficial. PMID:27112063

Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

PubMed

Denardo, Scott J; Vock, David M; Schmalfuss, Carsten M; Young, Gregory D; Tcheng, James E; O'Connor, Christopher M

2016-07-01

Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern. © 2016 American Heart Association, Inc.

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

Tumor necrosis factor alpha and pulmonary function in Saskatchewan grain handlers.

PubMed

McDuffie, Helen H; Nakagawa, Kazuko; Pahwa, Punam; Shindo, Junichi; Hashimoto, Mirai; Nakada, Naoyuki; Ghosh, Sunita; Kirychuk, Shelley P; Hucl, Pierre

2006-05-01

The objective of this study was to estimate the contribution of lifestyle (cigarettes) and tumor necrosis factor (TNF) alpha polymorphisms at position 308 of the tumor necrosis factor alpha gene promotor (TNF-308*1/*2) to pulmonary function among grain handlers. Employed male grain handlers (157) provided occupational and respiratory symptom information, pulmonary function measurements, and DNA for genotyping. The genotypes of 101 were TNF-308*1/*1, 47 were *1/*2, and nine were *2/*2. Current smokers whose genotype was *2/*2 or *1/*2 had lower values compared with other combinations of genotype and smoking status. Among *1/*1 homozygotes, current smokers had better percent of predicted forced expiratory volume in 1 second (P = 0.04) mean values than nonsmokers and better percent of predicted forced vital capacity than exsmokers (P = 0.017) or nonsmokers (P = 0.008). These results indicate the complexity of determining which workers will develop acute and chronic adverse pulmonary conditions in response to exposure to grain dust and the toxins in cigarette smoke interacting with their genotype.

Application of Near Infrared Spectroscopy, Intravascular Ultrasound and the Coronary Calcium Score to Predict Adverse Coronary Events

DTIC Science & Technology

2015-10-01

planned. 15. SUBJECT TERMS coronary artery disease , near infrared spectroscopy, calcium scoring, intravascular ultrasound 16. SECURIY CLASSIFICATION OF...Award Number: W81XWH-11-1-0831 TITLE: Application of Near Infrared Spectroscopy, Intravascular Ultrasound and the Coronary Calcium Score to...Predict Adverse Coronary Events PRINCIPAL INVESTIGATOR: Dr. Charles Lambert CONTRACTING ORGANIZATION: University Community Hospital Tampa, FL 33613

A High-yield Fall Risk and Adverse Events Screening Questions From the Stopping Elderly Accidents, Death, and Injuries (STEADI) Guideline for Older Emergency Department Fall Patients.

PubMed

Sri-On, Jiraporn; Tirrell, Gregory Philip; Kamsom, Anucha; Marill, Keith A; Shankar, Kalpana Narayan; Liu, Shan W

2018-03-25

The objectives were to examine whether responses to the Stopping Elderly Accidents, Death, and Injuries (STEADI) questions responses predicted adverse events after an older adult emergency department (ED) fall visits and to identify factors associated with such recurrent fall. We conducted a prospective study at two urban, teaching hospitals. We included patients aged ≥ 65 years who presented to the ED for an accidental fall. Data were gathered for fall-relevant comorbidities, high-risk medications for falls, and the responses to 12 questions from the STEADI guideline recommendation. Our outcomes were the number of 6-month adverse events that were defined as mortality, ED revisit, subsequent hospitalization, recurrent falls, and a composite outcome. There were 548 (86.3%) patients who completed follow-up and 243 (44.3%) patients experienced an adverse event after a fall within 6 months. In multivariate analysis, seven questions from the STEADI guideline predicted various outcomes. The question "Had previous fall" predicted recurrent falls (odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.52 to 3.97), the question "Feels unsteady when walking sometimes" (OR = 2.34, 95% CI = 1.44 to 3.81), and "Lost some feeling in their feet" predicted recurrent falls. In addition to recurrent falls risk, the supplemental questions "Use or have been advised to use a cane or walker," "Take medication that sometimes makes them feel light-headed or more tired than usual," "Take medication to help sleep or improve mood," and "Have to rush to a toilet" predicted other outcomes. A STEADI score of ≥4 did not predict adverse outcomes although seven individual questions from the STEADI guidelines were associated with increased adverse outcomes within 6 months. These may be organized into three categories (previous falls, physical activity, and high-risk medications) and may assist emergency physicians to evaluate and refer high-risk fall patients for a comprehensive falls evaluation. © 2018 by the Society for Academic Emergency Medicine.

Metabolic Profiles Predict Adverse Events Following Coronary Artery Bypass Grafting

PubMed Central

Shah, Asad A.; Craig, Damian M.; Sebek, Jacqueline K.; Haynes, Carol; Stevens, Robert C.; Muehlbauer, Michael J.; Granger, Christopher B.; Hauser, Elizabeth R.; Newby, L. Kristin; Newgard, Christopher B.; Kraus, William E.; Hughes, G. Chad; Shah, Svati H.

2012-01-01

Objectives Clinical models incompletely predict outcomes following coronary artery bypass grafting. Novel molecular technologies may identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. Methods The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected prior to surgery. Principal-components analysis and Cox proportional hazards regression modeling were used to assess the relation between metabolite factor levels and a composite outcome of post-coronary artery bypass grafting myocardial infarction, need for percutaneous coronary intervention, repeat coronary artery bypass grafting, or death. Results Over a mean follow-up of 4.3 ± 2.4 years, 126 subjects (26.4%) suffered an adverse event. Three principal-components analysis-derived factors were significantly associated with adverse outcome in univariable analysis: short-chain dicarboxylacylcarnitines (factor 2, P=0.001); ketone-related metabolites (factor 5, P=0.02); and short-chain acylcarnitines (factor 6, P=0.004). These three factors remained independently predictive of adverse outcome after multivariable adjustment: factor 2 (adjusted hazard ratio 1.23; 95% confidence interval [1.10-1.38]; P<0.001), factor 5 (1.17 [1.01-1.37], P=0.04), and factor 6 (1.14 [1.02-1.27], P=0.03). Conclusions Metabolic profiles are independently associated with adverse outcomes following coronary artery bypass grafting. These profiles may represent novel biomarkers of risk that augment existing tools for risk stratification of coronary artery bypass grafting patients and may elucidate novel biochemical pathways that mediate risk. PMID:22306227

Health Risks and Adverse Reactions to Functional Foods.

PubMed

Ameratunga, Rohan; Crooks, Christine; Simmons, Greg; Woon, See-Tarn

2016-01-01

Functional foods have become increasingly popular with consumers anxious to mitigate the effects of an unhealthy lifestyle or aging. In spite of attractive health claims, these products do not have legal or regulatory status in most countries and are regulated through their health claims. Regulation of functional foods by health claims does not address health risks and adverse effects of these products. In this essay regulatory aspects of functional foods are reviewed along with adverse effects published in the peer-reviewed literature. We detail why the lack of an internationally accepted definition of functional foods places consumers at risk of adverse outcomes. Our review will assist regulatory agencies, manufacturers and consumer groups to assess the benefits and reduce the risks associated with these products.

Predictive value of self-stigma, insight, and perceived adverse effects of medication for the clinical outcomes in patients with depressive disorders.

PubMed

Yen, Cheng-Fang; Lee, Yu; Tang, Tze-Chun; Yen, Ju-Yu; Ko, Chih-Hung; Chen, Cheng-Chung

2009-03-01

The aims of this prospective study were to examine the predictive values of self-stigma, insight, and perceived adverse effects of medication for remission of depressive symptoms, suicidal risk, and medication adherence in patients with depressive disorders over a 1-year follow-up period. One hundred seventy-four participants who were in a state of obvious depression underwent an index interview to determine their degree of self-stigma, insight, and perceived adverse effects of medication. One year later, they were reassessed to determine the severity of their depressive symptoms, suicidal risk, and the level of the medication adherence, and their associations with the 3 possible predictors at the index interview were examined. The results of this study indicated that perceiving more severe adverse effects of medication at the index interview increased the risks of the nonremission of depressive symptoms, occurrence of suicidal ideation or attempt, and medication nonadherence in patients with depressive disorders in the 1-year period. However, the degrees of self-stigma and insight did not predict the severity of depressive symptoms, suicidal risk, or the level of the medication adherence. Based on the results of this study, we suggest that it is important for clinicians to prevent the occurrence of and to help patients manage the adverse effects of medication. We also suggest that further prospective studies are needed to examine the predictive values of self-stigma and insight for clinical outcomes and medication adherence.

A path analysis of gender differences in adolescent onset of alcohol, tobacco and other drug use (ATOD), reported ATOD use and adverse consequences of ATOD use.

PubMed

Thomas, B S

1996-01-01

Gender differences in the ways a risk factor approach explains onset of using alcohol, tobacco and other drugs (ATOD), reported use of ATOD and adverse consequences from ATOD use were investigated by means of separate path analyses for male and female adolescents. A fully recursive model was specified in which alienation, trait anger, interaction anxiety and cognitive motivation for ATOD use comprised the first column variables which were used to predict earliness of onset. For the second step, column one variables plus onset were used to predict ATOD use. In the final step, column one variables plus onset and ATOD use were used to predict adverse consequences of ATOD use. An ex post facto design was used in surveying 796 high school students in a single Midwestern community. The data from this sample supported the predictive validity of the theoretical model. In addition to the expected indirect or mediated effects of the risk factors via onset of ATOD use on ATOD use and via onset and ATOD use on adverse consequences of ATOD use, there were direct effects of column on risk factors on both ATOD use and on adverse consequences of ATOD use for both males and females, lending support to the concept of multiple pathway risk factors. The three gender differences that emerged in the separate path analyses were entirely consistent with the gendered deviance model.

Contribution of new technologies to characterization and prediction of adverse effects.

PubMed

Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

2015-02-01

Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway concepts.

Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population.

PubMed

Schneuer, Francisco J; Roberts, Christine L; Guilbert, Cyrille; Simpson, Judy M; Algert, Charles S; Khambalia, Amina Z; Tasevski, Vitomir; Ashton, Anthony W; Morris, Jonathan M; Nassar, Natasha

2014-02-01

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy have been associated with adverse pregnancy outcomes in a few studies but not in other studies. We assessed the serum 25(OH)D concentration at 10-14 wk of pregnancy and its association with adverse pregnancy outcomes and examined the predictive accuracy. In this nested case-control study, we measured serum 25(OH)D in 5109 women with singleton pregnancies who were attending first-trimester screening in New South Wales, Australia. Multivariate logistic regression was conducted to examine the association between low 25(OH)D concentrations and adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, gestational diabetes, miscarriage, and stillbirth). The predictive accuracy of models was assessed. The median (IQR) 25(OH)D concentration for the total population was 56.4 nmol/L (43.3-69.8 nmol/L). Serum 25(OH)D concentrations showed significant variation by parity, smoking, weight, season of sampling, country of birth, and socioeconomic status. After adjustment for maternal and clinical risk factors, low 25(OH)D concentrations were not associated with most adverse pregnancy outcomes. The area under the receiver operating characteristic curve (AUC) and likelihood ratio for a composite of severe adverse pregnancy outcomes of 25(OH)D concentrations <25 nmol/L were 0.51 and 1.44, respectively, and, for risk factors alone, were 0.64 and 2.87, respectively. The addition of 25(OH)D information to maternal and clinical risk factors did not improve the ability to predict severe adverse pregnancy outcomes (AUC: 0.64; likelihood ratio: 2.32; P = 0.39). Low 25(OH)D serum concentrations in the first trimester of pregnancy are not associated with adverse pregnancy outcomes and do not predict complications any better than routinely assessed clinical and maternal risk-factor information.

The relationship between childhood adversity, attachment, and internalizing behaviors in a diversion program for child-to-mother violence.

PubMed

Nowakowski-Sims, Eva; Rowe, Amanda

2017-10-01

Very little research has been conducted on the role of childhood adversity in child-to-parent violence. Childhood adversity places youth at risk for internalizing behaviors (i.e. anxiety and depression) and externalizing behaviors (i.e. aggression). The purpose of this study was to explore the relationships between childhood adversity, child-mother attachment, and internalizing behaviors among a sample of 80 youth who have been arrested for domestic battery against a mother. This study reported high prevalence rates of childhood adversity (mean score of 10 out of 17 events). Multiple regression analysis indicated that insecure attachment predicted depression among females (F(6, 73)=4.87, p<0.001), and previous experience with child maltreatment and/or witness to parental violence predicted anxiety among females (F(6, 73)=3.08, p<0.01). This study is the first study to explore childhood adversity among a sample of perpetrators of child-to-mother violence and notably adds to our understanding of the multiple pathways connecting childhood adversity, child-mother attachment, and depression and anxiety among a difficult to treat youth population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defining sarcopenia in terms of incident adverse outcomes.

PubMed

Woo, Jean; Leung, Jason; Morley, J E

2015-03-01

The objectives of this study were to compare the performance of different diagnoses of sarcopenia using European Working Group on Sarcopenia in Older People, International Working Group on Sarcopenia, and the US Foundation of National Institutes of Health (FNIH) criteria, and the screening tool SARC-F, against the Asian Working Group for Sarcopenia consensus panel definitions, in predicting physical limitation, slow walking speed, and repeated chair stand performance, days of hospital stay and mortality at follow up. Longitudinal study. Community survey in Hong Kong. Participants were 4000 men and women 65 years and older living in the community. Information from questionnaire regarding activities of daily living, physical functioning limitations, and constituent questions of SARC-F; body mass index (BMI), grip strength (GS), walking speed, and appendicular muscle mass (ASM). FNIH, consensus panel definitions, and the screening tool SARC-F all have similar AUC values in predicting incident physical limitation and physical performance measures at 4 years, walking speed at 7 years, days of hospital stay at 7 years, and mortality at 10 years. None of the definitions predicted increase in physical limitation at 4 years or mortality at 10 years in women, and none predicted all the adverse outcomes. The highest AUC values were observed for walking speed at 4 and 7 years. When applied to a Chinese elderly population, criteria used for diagnosis of sarcopenia derived from European, Asian, and international consensus panels, from US cutoff values defined from incident physical limitation, and the SARC-F screening tool, all have similar performance in predicting incident physical limitation and mortality. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction.

PubMed

Mäkikallio, K; Räsänen, J; Mäkikallio, T; Vuolteenaho, O; Huhta, J C

2008-01-01

To determine whether low cardiovascular profile (CVP) score has prognostic value for predicting neonatal mortality and severe morbidity in human fetuses with growth restriction. Seventy-five consecutive growth-restricted fetuses with Doppler examination of cardiovascular hemodynamics within a week prior to delivery comprised the study population. Hydrops, heart size, cardiac function and venous and arterial hemodynamics were evaluated for CVP score. The primary outcome measures were neonatal mortality and cerebral palsy. During the neonatal period, six of 75 neonates died and two had cerebral palsy (Group 1, n = 8). Compared with the fetuses discharged home from hospital (Group 2, n = 67), those in Group 1 were delivered at an earlier gestational age (28 (range, 24-35) weeks vs. 35 (range, 26-40) weeks, P < 0.01) and had lower CVP scores (4 (range, 2-6) vs. 9 (range, 5-10), P < 0.0001). All CVP subscale scores were lower (P < 0.01) in Group 1 than in Group 2 fetuses. Gestational age-adjusted hazard ratios (95% CIs) for adverse neonatal outcome were highest for cardiomegaly (13.9 (1.7-114.3), P = 0.014), monophasic atrioventricular filling pattern or holosystolic tricuspid regurgitation (9.5 (2.3-38.4), P = 0.002) and atrial pulsations in the umbilical vein 7.7 (1.4-41.2), P = 0.017). Growth-restricted fetuses with adverse neonatal outcome have lower CVP scores than do fetuses with favorable neonatal outcome. The strongest predictors for adverse neonatal outcome in the CVP score were cardiomegaly, abnormal cardiac function with monophasic atrioventricular filling or holosystolic tricuspid regurgitation and increased systemic venous pressure. These assessments have independent prognostic power for adverse neonatal outcome even after adjustment for gestational age. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

Exploration of a Preflight Acuity Scale for Fixed Wing Air Ambulance Transport.

PubMed

Phipps, Marcy; Conley, Virginia; Constantine, William H

Despite the prevalence of fixed wing medical flights for specialized care and repatriation, few acuity rating scales exist aimed at the prediction of adverse in-flight medical events. An acuity scoring system can provide information to flight crews, allowing for staffing enhancements, protocol modifications, and flight planning, with the aim of improving patient care, outcomes, and preventing losses to providers because of costly diversions. Our medical crew developed an acuity scale, which was applied retrospectively to 296 patients transported between January 2016 and March 2017. Patients received scores based on conditions identified during the preflight medical report, the initial patient assessment, demographics, and flight factors. Five patients were identified as high-risk transports based on our scale. Three patients suffered adverse events according to our defined criteria, 2 of which occurred before transport and 1 during transport. The 3 patients suffering adverse events did not receive a score that indicated adverse events in flight. Our scale was not predictive of adverse events in flight. However, it did illuminate factors worthy of consideration. Consideration of these factors may have prevented adverse events. Published by Elsevier Inc.

A Decision Support Framework for Evaluation of Engineered ...

EPA Pesticide Factsheets

Engineered nanomaterials (ENM) are currently being developed and applied at rates that far exceed our ability to evaluate their potential for environmental or human health risks. The gap between material development and capacity for assessment grows wider every day. Transformative approaches are required that enhance our ability to forecast potential exposure and adverse health risks based on limited information such as the physical and chemical parameters of ENM, their proposed uses, and functional assays reflective of key ENM - environmental interactions. We are developing a framework that encompasses the potential for release of nanomaterials across a product life cycle, environmental transport, transformations and fate, exposure to sensitive species, including humans, and the potential for causing adverse effects. Each component of the framework is conceive of as a sequential segmented model depicting the movement, transformations and actions of ENM through environmental or biological compartments, and along which targeted functional assays can be developed that are indicative of projected rates of ENM movement or action. The eventual goal is to allow simple predictive models to be built that incorporate the data from key functional assays and thereby allow rapid screening of the projected margin of exposure for proposed applications of ENM enabled products. In this way, cases where a substantially safe margin of exposure is forecast can be reduced in

Early life adversity and adult biological risk profiles.

PubMed

Friedman, Esther M; Karlamangla, Arun S; Gruenewald, Tara L; Koretz, Brandon; Seeman, Teresa E

2015-01-01

To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. We analyzed data on 1180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States. ELA assessments were based on childhood socioeconomic disadvantage (i.e., on welfare, perceived low income, and less educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including than following: education, social relationships, and health behaviors. Childhood socioeconomic adversity and physical abuse were associated with increased AL (B = 0.094, standard error = 0.041, and B = 0.263, standard error = 0.091 respectively), with nonsignificant associations for parental divorce and death with AL. Adult education mediated the relationship between socioeconomic ELA and cumulative AL to the point of nonsignificance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable-adjusted analysis.

A Framework of Knowledge Integration and Discovery for Supporting Pharmacogenomics Target Predication of Adverse Drug Events: A Case Study of Drug-Induced Long QT Syndrome.

PubMed

Jiang, Guoqian; Wang, Chen; Zhu, Qian; Chute, Christopher G

2013-01-01

Knowledge-driven text mining is becoming an important research area for identifying pharmacogenomics target genes. However, few of such studies have been focused on the pharmacogenomics targets of adverse drug events (ADEs). The objective of the present study is to build a framework of knowledge integration and discovery that aims to support pharmacogenomics target predication of ADEs. We integrate a semantically annotated literature corpus Semantic MEDLINE with a semantically coded ADE knowledgebase known as ADEpedia using a semantic web based framework. We developed a knowledge discovery approach combining a network analysis of a protein-protein interaction (PPI) network and a gene functional classification approach. We performed a case study of drug-induced long QT syndrome for demonstrating the usefulness of the framework in predicting potential pharmacogenomics targets of ADEs.

External and internal factors influencing happiness in elite collegiate athletes.

PubMed

Denny, Katherine G; Steiner, Hans

2009-03-01

When under conditions of high demand and allostatic load, are happiness and satisfaction in four domains (family, friends, academics, recreation) influenced more by external or internal factors? Do student-athletes who lead exceedingly complicated lives report happiness as a function of athletic achievement or internal disposition? Stanford student-athletes (N=140) were studied with a standardized questionnaire which examined internal factors ((1) locus of control, (2) mindfulness, (3) self-restraint, and (4) self-esteem) to see whether they better account for happiness than external factors (playing time, scholarship). As predicted, internal factors were more powerful correlates of happiness when holding constant demographics. Regression models differed for different aspects of happiness, but the main postulated result of internal versus external was maintained throughout. These findings have implications for how well athletes cope with adversity which, in turn, could shed light on the development of traits that may provide a buffer against adversity and build resilience.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Technosocial Predictive Analytics in Support of Naturalistic Decision Making

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanfilippo, Antonio P.; Cowell, Andrew J.; Malone, Elizabeth L.

2009-06-23

A main challenge we face in fostering sustainable growth is to anticipate outcomes through predictive and proactive across domains as diverse as energy, security, the environment, health and finance in order to maximize opportunities, influence outcomes and counter adversities. The goal of this paper is to present new methods for anticipatory analytical thinking which address this challenge through the development of a multi-perspective approach to predictive modeling as a core to a creative decision making process. This approach is uniquely multidisciplinary in that it strives to create decision advantage through the integration of human and physical models, and leverages knowledgemore » management and visual analytics to support creative thinking by facilitating the achievement of interoperable knowledge inputs and enhancing the user’s cognitive access. We describe a prototype system which implements this approach and exemplify its functionality with reference to a use case in which predictive modeling is paired with analytic gaming to support collaborative decision-making in the domain of agricultural land management.« less

Sharply curved turn around duct flow predictions using spectral partitioning of the turbulent kinetic energy and a pressure modified wall law

NASA Technical Reports Server (NTRS)

Santi, L. Michael

1986-01-01

Computational predictions of turbulent flow in sharply curved 180 degree turn around ducts are presented. The CNS2D computer code is used to solve the equations of motion for two-dimensional incompressible flows transformed to a nonorthogonal body-fitted coordinate system. This procedure incorporates the pressure velocity correction algorithm SIMPLE-C to iteratively solve a discretized form of the transformed equations. A multiple scale turbulence model based on simplified spectral partitioning is employed to obtain closure. Flow field predictions utilizing the multiple scale model are compared to features predicted by the traditional single scale k-epsilon model. Tuning parameter sensitivities of the multiple scale model applied to turn around duct flows are also determined. In addition, a wall function approach based on a wall law suitable for incompressible turbulent boundary layers under strong adverse pressure gradients is tested. Turn around duct flow characteristics utilizing this modified wall law are presented and compared to results based on a standard wall treatment.

Anger, depression and anxiety associated with endothelial function in childhood and adolescence.

PubMed

Osika, W; Montgomery, S M; Dangardt, F; Währborg, P; Gan, L M; Tideman, E; Friberg, P

2011-01-01

Psychosocial adversity is a risk factor for cardiovascular disease (CVD) in adults. The authors assessed associations of reactive hyperaemia peripheral arterial tonometry (RH-PAT), a measure of endothelial function predictive of CVD, with self-assessed psychological health among school children. A total of 248 healthy school children (mean (SD) age 14.0 (1.0); 136 girls and 112 boys) underwent RH-PAT testing. They completed the Beck Youth Inventories (BYI) of emotional and social impairment scales, which is used to screen for depression, anxiety, anger and disruptive behaviour. No sex differences were observed for the RH-PAT score. Statistically significant differences were observed for the BYI scores; girls had higher scores for depression, anger and anxiety. Among the girls, there were statistically significant associations between lower RH-PAT scores and higher scores for anger (B coefficient=-0.100, p=0.040), depression (-0.108, p=0.009) and anxiety (-0.138, p=0.039) after adjustment for age. Among the boys, disruptive behaviour was associated with higher RH-PAT scores (0.09, p=0.006). The girls have higher levels of self-assessed anger; depression and anxiety compared with the boys, and these characteristics are associated with lower RH-PAT scores, indicating attenuated endothelial function. Among the boys, disruptive behaviour was associated with better endothelial function. Although psychological ill-health is associated with impaired endothelial function and CVD among adults, such processes may also be relevant to children. Psychosocial adversity in childhood might be a risk factor for subsequent CVD.

Admission hyperglycemia predicts inhospital mortality and major adverse cardiac events after primary percutaneous coronary intervention in patients without diabetes mellitus.

PubMed

Ekmekci, Ahmet; Cicek, Gokhan; Uluganyan, Mahmut; Gungor, Baris; Osman, Faizel; Ozcan, Kazim Serhan; Bozbay, Mehmet; Ertas, Gokhan; Zencirci, Aycan; Sayar, Nurten; Eren, Mehmet

2014-02-01

Admission hyperglycemia is associated with high inhospital and long-term adverse events in patients that undergo primary percutaneous coronary intervention (PCI). We aimed to evaluate whether hyperglycemia predicts inhospital mortality. We prospectively analyzed 503 consecutive patients. The patients were divided into tertiles according to the admission glucose levels. Tertile I: glucose <118 mg/dL (n = 166), tertile II: glucose 118 to 145 mg/dL (n = 168), and tertile III: glucose >145 mg/dL (n = 169). Inhospital mortality was 0 in tertile I, 2 in tertile II, and 9 in tertile III (P < .02). Cardiogenic shock occurred more frequently in tertile III compared to tertiles I and II (10% vs 4.1% and 0.6%, respectively, P = .01). Multivariate logistic regression analysis revealed that patients in tertile III had significantly higher risk of inhospital major adverse cardiac events compared to patients in tertile I (odds ratio: 9.55, P < .02). Admission hyperglycemia predicts inhospital adverse cardiac events in mortality and acute ST-segment elevation myocardial infarction in patients that underwent primary PCI.

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

PubMed

Johansson, Gunnar; Lindberg, Anne; Romberg, Kerstin; Nordström, Lars; Gerken, Fronke; Roquet, Annika

2008-09-01

Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. Compared with placebo, tiotropium improved lung function in patients with mild COPD.

Efficacy and Safety of Inhaled Aztreonam Lysine for Airway Pseudomonas in Cystic Fibrosis

PubMed Central

Retsch-Bogart, George Z.; Quittner, Alexandra L.; Gibson, Ronald L.; Oermann, Christopher M.; McCoy, Karen S.; Montgomery, A. Bruce; Cooper, Peter J.

2009-01-01

Background: We assessed the short-term efficacy and safety of aztreonam lysine for inhalation (AZLI [an aerosolized monobactam antibiotic]) in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) airway infection. Methods: In this randomized, double-blind, placebo-controlled, international study (AIR-CF1 trial; June 2005 to April 2007), patients (n = 164; ≥ 6 years of age) with FEV1 ≥ 25% and ≤ 75% predicted values, and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI (three times daily for 28 days) or placebo (1:1 randomization), then were monitored for 14 days after study drug completion. The primary efficacy end point was change in patient-reported respiratory symptoms (CF-Questionnaire-Revised [CFQ-R] Respiratory Scale). Secondary end points included changes in pulmonary function (FEV1), sputum PA density, and nonrespiratory CFQ-R scales. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. Results: After 28 days of treatment, AZLI improved the mean CFQ-R respiratory score (9.7 points; p < 0.001), FEV1 (10.3% predicted; p < 0.001), and sputum PA density (− 1.453 log10 cfu/g; p < 0.001), compared with placebo. Significant improvements in Eating, Emotional Functioning, Health Perceptions, Physical Functioning, Role Limitation/School Performance, and Vitality CFQ-R scales were observed. Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of “productive cough” was reduced by half in AZLI-treated patients. PA aztreonam susceptibility at baseline and end of therapy were similar. Conclusions: In patients with CF, PA airway infection, moderate-to-severe lung disease, and no recent use of antipseudomonal antibiotics or azithromycin, 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function, and was well tolerated. Trial registration: Clinicaltrials.gov Identifier: NCT00112359 PMID:19420195

Neuropsychological functioning, age, and medication adherence in bipolar disorder

PubMed Central

Raust, Aurélie; Etain, Bruno; Guillot, Romain; Job, Sophie; Loftus, Joséphine; Médecin, Isabelle; Bougerol, Thierry; Polosan, Mircea; Fredembach, Benjamin; Gard, Sébastien; M’Bailara, Katia; Kahn, Jean-Pierre; Roux, Paul; Homassel, Anne-Sophie; Carminati, Mathilde; Matos, Lucile; Olié, Emilie; Bellivier, Frank; Courtet, Philippe; Henry, Chantal; Leboyer, Marion; Azorin, Jean-Michel; Belzeaux, Raoul

2017-01-01

Objectives Poor adherence to medication is frequent in bipolar disorder (BD) and has been associated with several factors. To date, the relationship between low adherence and neuropsychological functioning in BD is still unclear. As age and neuropsychological functioning might have opposing influences on adherence, our aim was to investigate this link with a particular focus on the effect of age. Methods In a cross-sectional study, we included 353 patients divided into two age-groups (16–46; 47–71) from a French cohort diagnosed with BD (type I, II, NOS) and strictly euthymic. All patients had a standardized clinical and neuropsychological assessment and were categorized as high (n = 186) or low (n = 167) adherent based on their score from the Medication Adherence Rating Scale. Clinical information was collected based on a standardized interview and clinical validated scales. Neuropsychological performances were evaluated with an established standardized neuropsychological battery for bipolar disorder patients. After univariate analysis, neuropsychological and clinical predictors of low adherence were included in two age-specific stepwise multiple logistic regressions. Results A smaller number of hospitalizations (OR = 0.846, p = 0.012), a shorter illness duration (OR = 0.937, p = 0.003) and higher adverse effects (OR = 1.082, p<0.001) were associated with a greater risk of low adherence in the younger patients. In the older patients, low adherence was also predicted by a smaller number of hospitalizations (OR = 0.727, p = 0.008) and higher adverse effects (OR = 1.124, p = 0.005). Interestingly poor inhibition performance was also a significant predictor of low adherence in older patients (OR = 0.924, p = 0.030). Conclusions We found an age-specific relationship between cognitive functioning and adherence in patients with BD. Poor inhibition performances predicted low adherence in older patients only. Our results highlight the need to provide age-adapted therapeutic interventions to improve adherence in patients with BD. PMID:28873468

The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

PubMed

Zhang, Huihui; Li, Jie; Yang, Bei; Ji, Tao; Long, Zhouting; Xing, Qiquan; Shao, Di; Bai, Huayu; Sun, Jiwei; Cao, Fenglin

2018-02-01

Catechol-O-methyltransferase (COMT) Val 158 Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val 158 Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val 158 Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η 2 =0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η 2 =0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta‐analysis

PubMed Central

De Boer, M. A.; Heymans, M. W.; Schoonmade, L. J.; Bossuyt, P. M. M.; Mol, B. W. J.; De Groot, C. J. M.; Bax, C. J.

2018-01-01

ABSTRACT Objective Doppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler. Methods PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies‐2) tool. Meta‐analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver–operating characteristics meta‐regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly. Results The search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse than did UA Doppler in the prediction of low Apgar score (P = 0.017) and emergency delivery for fetal distress (P = 0.034). CPR outperformed MCA Doppler in the prediction of composite adverse outcome (P < 0.001) and emergency delivery for fetal distress (P = 0.013). Conclusion Calculating the CPR with MCA Doppler can add value to UA Doppler assessment in the prediction of adverse perinatal outcome in women with a singleton pregnancy. However, it is unclear to which subgroup of pregnant women this applies. The effectiveness of the CPR in guiding clinical management needs to be evaluated in clinical trials. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. PMID:28708272

Epileptic Seizures Prediction Using Machine Learning Methods

PubMed Central

Usman, Syed Muhammad

2017-01-01

Epileptic seizures occur due to disorder in brain functionality which can affect patient's health. Prediction of epileptic seizures before the beginning of the onset is quite useful for preventing the seizure by medication. Machine learning techniques and computational methods are used for predicting epileptic seizures from Electroencephalograms (EEG) signals. However, preprocessing of EEG signals for noise removal and features extraction are two major issues that have an adverse effect on both anticipation time and true positive prediction rate. Therefore, we propose a model that provides reliable methods of both preprocessing and feature extraction. Our model predicts epileptic seizures' sufficient time before the onset of seizure starts and provides a better true positive rate. We have applied empirical mode decomposition (EMD) for preprocessing and have extracted time and frequency domain features for training a prediction model. The proposed model detects the start of the preictal state, which is the state that starts few minutes before the onset of the seizure, with a higher true positive rate compared to traditional methods, 92.23%, and maximum anticipation time of 33 minutes and average prediction time of 23.6 minutes on scalp EEG CHB-MIT dataset of 22 subjects. PMID:29410700

Robust and Adaptive Online Time Series Prediction with Long Short-Term Memory

PubMed Central

Tao, Qing

2017-01-01

Online time series prediction is the mainstream method in a wide range of fields, ranging from speech analysis and noise cancelation to stock market analysis. However, the data often contains many outliers with the increasing length of time series in real world. These outliers can mislead the learned model if treated as normal points in the process of prediction. To address this issue, in this paper, we propose a robust and adaptive online gradient learning method, RoAdam (Robust Adam), for long short-term memory (LSTM) to predict time series with outliers. This method tunes the learning rate of the stochastic gradient algorithm adaptively in the process of prediction, which reduces the adverse effect of outliers. It tracks the relative prediction error of the loss function with a weighted average through modifying Adam, a popular stochastic gradient method algorithm for training deep neural networks. In our algorithm, the large value of the relative prediction error corresponds to a small learning rate, and vice versa. The experiments on both synthetic data and real time series show that our method achieves better performance compared to the existing methods based on LSTM. PMID:29391864

Robust and Adaptive Online Time Series Prediction with Long Short-Term Memory.

PubMed

Yang, Haimin; Pan, Zhisong; Tao, Qing

2017-01-01

Online time series prediction is the mainstream method in a wide range of fields, ranging from speech analysis and noise cancelation to stock market analysis. However, the data often contains many outliers with the increasing length of time series in real world. These outliers can mislead the learned model if treated as normal points in the process of prediction. To address this issue, in this paper, we propose a robust and adaptive online gradient learning method, RoAdam (Robust Adam), for long short-term memory (LSTM) to predict time series with outliers. This method tunes the learning rate of the stochastic gradient algorithm adaptively in the process of prediction, which reduces the adverse effect of outliers. It tracks the relative prediction error of the loss function with a weighted average through modifying Adam, a popular stochastic gradient method algorithm for training deep neural networks. In our algorithm, the large value of the relative prediction error corresponds to a small learning rate, and vice versa. The experiments on both synthetic data and real time series show that our method achieves better performance compared to the existing methods based on LSTM.

Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

ERIC Educational Resources Information Center

Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

2010-01-01

Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

Gender differences in job strain, effort-reward imbalance, and health functioning among Chinese physicians.

PubMed

Li, Jian; Yang, Wenjie; Cho, Sung-Il

2006-03-01

To examine the association between work stress measured by job strain and effort-reward imbalance (ERI) and health functioning in a sample of hospital-based Chinese physicians, a self-reported survey with a standardized questionnaire was conducted in three hospitals in China, among 256 men and 266 women. It was found that both job strain and ERI were associated with impaired health functioning in men and women, but that ERI indicated a stronger association. Men's job control was significantly higher, and was related to men's physical health; whereas women perceived relatively higher job reward which predicted women's mental health. The findings provide evidence of the adverse effects on health functioning of both job strain and ERI, but ERI appears to have more explanatory power as a model of work stress in this sample of Chinese physicians. In addition, gender differences of work stress with respect to health are present.

Impact of Procedure-Related Complications on Long-term Islet Transplantation Outcome.

PubMed

Caiazzo, Robert; Vantyghem, Marie-Christine; Raverdi, Violeta; Bonner, Caroline; Gmyr, Valery; Defrance, Frederique; Leroy, Clara; Sergent, Geraldine; Hubert, Thomas; Ernst, Oliver; Noel, Christian; Kerr-Conte, Julie; Pattou, François

2015-05-01

Pancreatic islet transplantation offers a promising biotherapy for the treatment of type 1 diabetes, but this procedure has met significant challenges over the years. One such challenge is to address why primary graft function still remains inconsistent after islet transplantation. Several variables have been shown to affect graft function, but the impact of procedure-related complications on primary and long-term graft functions has not yet been explored. Twenty-six patients with established type 1 diabetes were included in this study. Each patient had two to three intraportal islet infusions to obtain 10,000 islet equivalent (IEQ)/kg in body weight, equaling a total of 68 islet infusions. Islet transplantation consisted of three sequential fresh islet infusions within 3 months. Islet infusions were performed surgically or under ultrasound guidance, depending on patient morphology, availability of the radiology suite, and patient medical history. Prospective assessment of adverse events was recorded and graded using "Common Terminology Criteria for adverse events in Trials of Adult Pancreatic Islet Transplantation." There were no deaths or patients dropouts. Early complications occurred in nine of 68 procedures. β score 1 month after the last graft and optimal graft function (β score ≥7) rate were significantly lower in cases of procedure-related complications (P = 0.02, P = 0.03). Procedure-related complications negatively impacted graft function (P = 0.009) and was an independent predictive factor of long-term graft survival (P = 0.033) in multivariate analysis. Complications occurring during radiologic or surgical intraportal islet transplantation significantly impair primary graft function and graft survival regardless of their severity.

Do race, neglect, and childhood poverty predict physical health in adulthood? A multilevel prospective analysis.

PubMed

Nikulina, Valentina; Widom, Cathy Spatz

2014-03-01

Childhood neglect and poverty often co-occur and both have been linked to poor physical health outcomes. In addition, Blacks have higher rates of childhood poverty and tend to have worse health than Whites. This paper examines the unique and interacting effects of childhood neglect, race, and family and neighborhood poverty on adult physical health outcomes. This prospective cohort design study uses a sample (N=675) of court-substantiated cases of childhood neglect and matched controls followed into adulthood (M(age)=41). Health indicators (C-Reactive Protein [CRP], hypertension, and pulmonary functioning) were assessed through blood collection and measurements by a registered nurse. Data were analyzed using hierarchical linear models to control for clustering of participants in childhood neighborhoods. Main effects showed that growing up Black predicted CRP and hypertension elevations, despite controlling for neglect and childhood family and neighborhood poverty and their interactions. Multivariate results showed that race and childhood adversities interacted to predict adult health outcomes. Childhood family poverty predicted increased risk for hypertension for Blacks, not Whites. In contrast, among Whites, childhood neglect predicted elevated CRP. Childhood neighborhood poverty interacted with childhood family poverty to predict pulmonary functioning in adulthood. Gender differences in health indicators were also observed. The effects of childhood neglect, childhood poverty, and growing up Black in the United States are manifest in physical health outcomes assessed 30 years later. Implications are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Previous Institutionalization Is Followed by Broader Amygdala-Hippocampal-PFC Network Connectivity during Aversive Learning in Human Development.

PubMed

Silvers, Jennifer A; Lumian, Daniel S; Gabard-Durnam, Laurel; Gee, Dylan G; Goff, Bonnie; Fareri, Dominic S; Caldera, Christina; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Tottenham, Nim

2016-06-15

Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience. Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function. Copyright © 2016 the authors 0270-6474/16/366421-11$15.00/0.

The impact of a long asylum procedure on quality of life, disability and physical health in Iraqi asylum seekers in the Netherlands.

PubMed

Laban, Cornelis J; Komproe, Ivan H; Gernaat, Hajo B P E; de Jong, Joop T V M

2008-07-01

Refugees in western countries often face long juridical procedures before their requests for a resident permit is granted. The, still scanty, literature shows high prevalence rates of psychopathology among asylum seekers, but there has been little interest for other impaired dimensions of health. The present study is part of a community-based mental health survey among Iraqi asylum seekers in the Netherlands, conducted between November 2000 and September 2001, on the risks of a long asylum procedure. The objectives of this study were to explore quality of life (QoL), disability and physical health and their relationships with psychopathology and pre- and post-migration variables. Two groups of pre-stratified (length of asylum procedure), randomly selected Iraqi asylum seekers (N = 143 and N = 151), were interviewed with fully structured, culturally validated questionnaires. Quality of life was examined with QoLWHO-Bref, functional disability with the Brief Disability Questionnaire and physical health with a newly developed questionnaire. Psychiatric (DSM IV) disorders were measured with the WHO Composite International Diagnostic Interview 2.1. Multivariate logistic regression analyses were used to estimate the relationships between the outcome measures and socio-demographics, adverse life events in Iraq, post-migration living problems (PMLP) and psychopathology. Respondents with a long asylum procedure reported significantly lower QoL, higher functional disability and more physical complaints. Multivariate regression shows that length of stay is the strongest predictor for a low overall QoL. In addition, lower QoL was predicted by psychopathology, higher age, adverse life events in the Netherlands and the PMLP-clusters: family issues, socio-economic living conditions and socio-religious aspects. Disability was predicted by psychopathology, higher age and the PMLP clusters: family issues and socio-religious aspects. Physical complaints were predicted by length of asylum procedure, psychopathology, female sex, adverse life events in Iraq and PMLP-family issues. A long asylum procedure has a negative impact on the overall health situation and the QoL of asylum seekers. The situation is not only harming the affected, but also interferes with the integration process in the Netherlands or elsewhere. The findings are important for health professionals, governments and human right specialists.

Diet matters: Glucocorticoid-related neuroadaptations associated with calorie intake in female rhesus monkeys.

PubMed

Godfrey, Jodi R; Diaz, Maylen Perez; Pincus, Melanie; Kovacs-Balint, Zsofia; Feczko, Eric; Earl, Eric; Miranda-Dominguez, Oscar; Fair, Damien; Sanchez, Mar M; Wilson, Mark E; Michopoulos, Vasiliki

2018-05-01

Exposure to psychosocial stressors increases consumption of palatable, calorically dense diets (CDD) and the risk for obesity, especially in females. While consumption of an obesogenic diet and chronic stress have both been shown to decrease dopamine 2 receptor (D2R) binding and alter functional connectivity (FC) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc), it remains uncertain how social experience and dietary environment interact to affect reward pathways critical for the regulation of motivated behavior. Using positron emission tomography (PET) and resting state functional connectivity magnetic resonance neuroimaging (rs-fMRI), in female rhesus monkeys maintained in a low calorie chow (n = 18) or a dietary choice condition (chow and a CDD; n = 16) for 12 months, the current study tested the overarching hypothesis that the adverse social experience resulting from subordinate social status would interact with consumption of an obesogenic diet to increase caloric intake that would be predicted by greater cortisol, lower prefrontal D2R binding potential (D2R-BP) and lower PFC-NAcc FC. Results showed that the consequences of adverse social experience imposed by chronic social subordination vary significantly depending on the dietary environment and are associated with alterations in prefrontal D2R-BP and FC in NAcc-PFC sub-regions that predict differences in caloric intake, body weight gain, and fat accumulation. Higher levels of cortisol in the chow-only condition were associated with mild inappetence, as well as increased orbitofrontal (OFC) D2R-BP and greater FC between the NAcc and the dorsolateral PFC (dlPFC) and ventromedial PFC (vmPFC). However, increased cortisol release in females in the dietary choice condition was associated with reduced prefrontal D2R-BP, and opposite FC between the NAcc and the vmPFC and dlPFC observed in the chow-only females. Importantly, the degree of these glucocorticoid-related neuroadaptations predicted significantly more total calorie intake as well as more consumption of the CDD for females having a dietary choice, but had no relation to calorie intake in the chow-only condition. Overall, the current findings suggest that dietary environment modifies the consequences of adverse social experience on reward pathways and appetite regulation and, in an obesogenic dietary environment, may reflect impaired cognitive control of food intake. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictive factors of short term outcome after liver transplantation: A review

PubMed Central

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-01-01

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function. PMID:27468188

Predictive factors of short term outcome after liver transplantation: A review.

PubMed

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-07-14

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.

PubMed

Bhat, Amritha; Grote, Nancy K; Russo, Joan; Lohr, Mary Jane; Jung, Hyunzee; Rouse, Caroline E; Howell, Elaine C; Melville, Jennifer L; Carson, Kathy; Katon, Wayne

2017-01-01

The study examined the effectiveness of a perinatal collaborative care intervention in moderating the effects of adverse neonatal birth events on risks of postpartum depressive symptoms and impaired functioning among women of lower socioeconomic status with antenatal depression. A randomized controlled trial with blinded outcome assessments was conducted in ten public health centers, comparing MOMCare (choice of brief interpersonal psychotherapy, pharmacotherapy, or both) with intensive maternity support services (MSS-Plus). Participants had probable diagnoses of major depressive disorder or dysthymia during pregnancy. Generalized estimating equations estimated differences in depression and functioning measures between groups with and without adverse birth events within the treatment arms. A total of 160 women, 43% of whom experienced at least one adverse birth event, were included in the analyses. For women who received MOMCare, postpartum depression scores (measured with the Symptom Checklist-20) did not differ by whether or not they experienced an adverse birth event (mean±SD scores of .86±.51 for mothers with an adverse birth event and .83±.56 for mothers with no event; p=.78). For women who received MSS-Plus, having an adverse birth event was associated with persisting depression in the postpartum period (mean scores of 1.20±.0.61 for mothers with an adverse birth event and .93±.52 for mothers without adverse birth event; p=.04). Similar results were seen for depression response rates and functioning. MOMCare mitigated the risk of postpartum depressive symptoms and impaired functioning among women of low socioeconomic status who had antenatal depression and who experienced adverse birth events.

Building gene expression signatures indicative of transcription factor activation to predict AOP modulation

EPA Science Inventory

Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

Adverse life events, psychiatric history, and biological predictors of postpartum depression in an ethnically diverse sample of postpartum women.

PubMed

Guintivano, J; Sullivan, P F; Stuebe, A M; Penders, T; Thorp, J; Rubinow, D R; Meltzer-Brody, S

2018-05-01

Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case-control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry. We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD. This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids. Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.

The Identification of Seniors at Risk (ISAR) score to predict clinical outcomes and health service costs in older people discharged from UK acute medical units.

PubMed

Edmans, Judi; Bradshaw, Lucy; Gladman, John R F; Franklin, Matthew; Berdunov, Vladislav; Elliott, Rachel; Conroy, Simon P

2013-11-01

tools are required to identify high-risk older people in acute emergency settings so that appropriate services can be directed towards them. to evaluate whether the Identification of Seniors At Risk (ISAR) predicts the clinical outcomes and health and social services costs of older people discharged from acute medical units. an observational cohort study using receiver-operator curve analysis to compare baseline ISAR to an adverse clinical outcome at 90 days (where an adverse outcome was any of death, institutionalisation, hospital readmission, increased dependency in activities of daily living (decrease of 2 or more points on the Barthel ADL Index), reduced mental well-being (increase of 2 or more points on the 12-point General Health Questionnaire) or reduced quality of life (reduction in the EuroQol-5D) and high health and social services costs over 90 days estimated from routine electronic service records. two acute medical units in the East Midlands, UK. a total of 667 patients aged ≥70 discharged from acute medical units. an adverse outcome at 90 days was observed in 76% of participants. The ISAR was poor at predicting adverse outcomes (AUC: 0.60, 95% CI: 0.54-0.65) and fair for health and social care costs (AUC: 0.70, 95% CI: 0.59-0.81). adverse outcomes are common in older people discharged from acute medical units in the UK; the poor predictive ability of the ISAR in older people discharged from acute medical units makes it unsuitable as a sole tool in clinical decision-making.

The inter- and intra- generational transmission of family poverty and hardship (adversity): A prospective 30 year study

PubMed Central

Bor, William; Ahmadabadi, Zohre; Williams, Gail M.; Alati, Rosa; Mamun, Abdullah A.; Scott, James G.; Clavarino, Alexandra M.

2018-01-01

Background Children exposed to family poverty have been found to have higher morbidity and mortality rates, poorer mental health and cognitive outcomes and reduced life chances across a wide range of life domains. There is, however, very little known about the extent to which poverty is experienced by children over their early life course, particularly in community samples. This study tracks changes in family poverty and the main factors that predict family poverty (adverse life experiences) over a 30-year period since the birth of the study child. Methods Data are from a prospective, longitudinal, birth cohort study conducted in Brisbane, Australia. Consecutive families were recruited at the mothers’ first obstetrical visit at one of two major obstetrical hospitals in Brisbane. Data are available for 2087 families with complete data at the 30-year follow-up. Poverty was measured using family income at each time point (adjusted for inflation). Findings Poverty affects about 20% of families at any time point. It is common for families to move in and out of poverty, as their circumstances are affected by such adversities as unemployment and marital breakdown. Over the period of the study about half the families in the study experienced poverty on at least one occasion. Only a very small minority of families experienced persistent poverty over the 30-year duration of the study. Logistic regressions with time lag show that family poverty predicts subsequent adversities and adverse events predict subsequent poverty. Conclusions Experiences of poverty and adversity are common and may vary greatly over the child’s early life course. In assessing the health consequences of poverty, it is important to distinguish the timing and chronicity of early life course experiences of poverty and adversity. PMID:29360828

The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

PubMed

Van Den Berg, Patricia; Body, Richard

2018-03-01

The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

The inter- and intra- generational transmission of family poverty and hardship (adversity): A prospective 30 year study.

PubMed

Najman, Jake M; Bor, William; Ahmadabadi, Zohre; Williams, Gail M; Alati, Rosa; Mamun, Abdullah A; Scott, James G; Clavarino, Alexandra M

2018-01-01

Children exposed to family poverty have been found to have higher morbidity and mortality rates, poorer mental health and cognitive outcomes and reduced life chances across a wide range of life domains. There is, however, very little known about the extent to which poverty is experienced by children over their early life course, particularly in community samples. This study tracks changes in family poverty and the main factors that predict family poverty (adverse life experiences) over a 30-year period since the birth of the study child. Data are from a prospective, longitudinal, birth cohort study conducted in Brisbane, Australia. Consecutive families were recruited at the mothers' first obstetrical visit at one of two major obstetrical hospitals in Brisbane. Data are available for 2087 families with complete data at the 30-year follow-up. Poverty was measured using family income at each time point (adjusted for inflation). Poverty affects about 20% of families at any time point. It is common for families to move in and out of poverty, as their circumstances are affected by such adversities as unemployment and marital breakdown. Over the period of the study about half the families in the study experienced poverty on at least one occasion. Only a very small minority of families experienced persistent poverty over the 30-year duration of the study. Logistic regressions with time lag show that family poverty predicts subsequent adversities and adverse events predict subsequent poverty. Experiences of poverty and adversity are common and may vary greatly over the child's early life course. In assessing the health consequences of poverty, it is important to distinguish the timing and chronicity of early life course experiences of poverty and adversity.

New classification system for indications for endoscopic retrograde cholangiopancreatography predicts diagnoses and adverse events.

PubMed

Yuen, Nicholas; O'Shaughnessy, Pauline; Thomson, Andrew

2017-12-01

Indications for endoscopic retrograde cholangiopancreatography (ERCP) have received little attention, especially in scientific or objective terms. To review the prevailing ERCP indications in the literature, and to propose and evaluate a new ERCP indication system, which relies on more objective pre-procedure parameters. An analysis was conducted on 1758 consecutive ERCP procedures, in which contemporaneous use was made of an a-priori indication system. Indications were based on the objective pre-procedure parameters and divided into primary [cholangitis, clinical evidence of biliary leak, acute (biliary) pancreatitis, abnormal intraoperative cholangiogram (IOC), or change/removal of stent for benign/malignant disease] and secondary [combination of two or three of: pain attributable to biliary disease ('P'), imaging evidence of biliary disease ('I'), and abnormal liver function tests (LFTs) ('L')]. A secondary indication was only used if a primary indication was not present. The relationship between this newly developed classification system and ERCP findings and adverse events was examined. The indications of cholangitis and positive IOC were predictive of choledocholithiasis at ERCP (101/154 and 74/141 procedures, respectively). With respect to secondary indications, only if all three of 'P', 'I', and 'L' were present there was a statistically significant association with choledocholithiasis (χ 2 (1) = 35.3, p < .001). Adverse events were associated with an unusual indication leading to greater risk of unplanned hospitalization (χ 2 (1) = 17.0, p < .001). An a-priori-based indication system for ERCP, which relies on pre-ERCP objective parameters, provides a more useful and scientific classification system than is available currently.

Normal stress-only myocardial single photon emission computed tomography predicts good outcome in patients with coronary artery stenoses between 40 and 70.

PubMed

Jiang, Zhixin; Liu, Yangqing; Xin, Chaofan; Zhou, Yanli; Wang, Cheng; Zhao, Zhongqiang; Li, Chunxiang; Li, Dianfu

2016-09-01

Normal stress myocardial single photon emission computed tomography (SPECT) usually indicates good physiologic function of all coronary lesions, and also indicates a good outcome. We hypothesize that it can still predict good outcome in patients with coronary stenoses between 40 and 70%. A group of patients who underwent stress myocardial SPECT after coronary angiography were consecutively recruited in our center. Patients were eligible if they had one or more coronary stenoses between 40 and 70%. Patients with coronary stenoses greater than 50% diameter of left main or greater than 70% diameter of nonleft main epicardial vessels, and left ventricular ejection fraction less than 50% were excluded. The outcome was defined as major adverse events, including cardiac death, nonfatal myocardial infarction, and revascularization. Patients' survival curves were constructed accorded to the method of Kaplan and Meier and compared using the log-rank test. A study cohort of 77 patients was enrolled. According to the summed stress score, 43 patients were assigned to the perfusion defect group and 34 patients were assigned to the perfusion normal group. The follow-up duration was 6.4±0.3 years. In the perfusion normal group, only one of 34 (2.9%) patients developed major adverse events. In the perfusion defect group, six of 43 (14%) developed major adverse events, P-value of 0.041. It is safe to defer a percutaneous coronary intervention in patients with coronary stenoses between 40 and 70% and normal stress myocardial SPECT.

Comparative Approaches to Understanding the Relation Between Aging and Physical Function

PubMed Central

Cesari, Matteo; Seals, Douglas R.; Shively, Carol A.; Carter, Christy S.

2016-01-01

Despite dedicated efforts to identify interventions to delay aging, most promising interventions yielding dramatic life-span extension in animal models of aging are often ineffective when translated to clinical trials. This may be due to differences in primary outcomes between species and difficulties in determining the optimal clinical trial paradigms for translation. Measures of physical function, including brief standardized testing batteries, are currently being proposed as biomarkers of aging in humans, are predictive of adverse health events, disability, and mortality, and are commonly used as functional outcomes for clinical trials. Motor outcomes are now being incorporated into preclinical testing, a positive step toward enhancing our ability to translate aging interventions to clinical trials. To further these efforts, we begin a discussion of physical function and disability assessment across species, with special emphasis on mice, rats, monkeys, and man. By understanding how physical function is assessed in humans, we can tailor measurements in animals to better model those outcomes to establish effective, standardized translational functional assessments with aging. PMID:25910845

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

Short-term effects of air pollution, markers of endothelial activation, and coagulation to predict major adverse cardiovascular events in patients with acute coronary syndrome: insights from AIRACOS study.

PubMed

Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Rodríguez, Sergio; Avanzas, Pablo; Juarez-Prera, Ruben A

2017-07-01

The aim of this study was to determine whether markers of inflammation and coagulation are associated with short-term particulate matter exposure and predict major adverse cardiovascular events at 360 d in patients with acute coronary syndrome (ACS). We included 307 consecutive patients, and assessed the average concentrations of data on atmospheric pollution in ambient air and meteorological variables from 1 d up to 7 d prior to admission. In patients with ACS, the markers of endothelial activation and coagulation, but not black carbon exposure, are associated with major adverse cardiovascular events at one-year follow-up.

20170312 - Adverse Outcome Pathway (AOP) framework for ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse Outcome Pathway (AOP) framework for embryonic ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse outcomes in older adults attending emergency departments: a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool.

PubMed

Galvin, Rose; Gilleit, Yannick; Wallace, Emma; Cousins, Gráinne; Bolmer, Manon; Rainer, Timothy; Smith, Susan M; Fahey, Tom

2017-03-01

older adults are frequent users of emergency services and demonstrate high rates of adverse outcomes following emergency care. to perform a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool, to determine its predictive value in identifying adults ≥65 years at risk of functional decline, unplanned emergency department (ED) readmission, emergency hospitalisation or death within 180 days after index ED visit/hospitalisation. a systematic literature search was conducted in PubMed, EMBASE, CINAHL, EBSCO and the Cochrane Library to identify validation and impact analysis studies of the ISAR tool. A pre-specified ISAR score of ≥2 (maximum score 6 points) was used to identify patients at high risk of adverse outcomes. A bivariate random effects model generated pooled estimates of sensitivity and specificity. Statistical heterogeneity was explored and methodological quality was assessed using validated criteria. thirty-two validation studies (n = 12,939) are included. At ≥2, the pooled sensitivity of the ISAR for predicting ED return, emergency hospitalisation and mortality at 6 months is 0.80 (95% confidence interval (CI) 0.70-0.87), 0.82 (95% CI 0.74-0.88) and 0.87 (95% CI 0.75-0.94), respectively, with a pooled specificity of 0.31 (95% CI 0.24-0.38), 0.32 (95% CI 0.24-0.41) and 0.35 (95% CI 0.26-0.44). Similar values are demonstrated at 30 and 90 days. Three heterogeneous impact analysis studies examined the clinical implementation of the ISAR and reported mixed findings across patient and process outcomes. the ISAR has modest predictive accuracy and may serve as a decision-making adjunct when determining which older adults can be safely discharged. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cumulative adversity in childhood and emergent risk factors for long-term health.

PubMed

Slopen, Natalie; Koenen, Karestan C; Kubzansky, Laura D

2014-03-01

To examine whether and when effects of cumulative adversity in the first 7 years of life are evident in relation to 3 childhood markers of risk for poor adult physical health. The study data are from an English birth cohort. Parental reports of 8 social risk factors were obtained during the child's first 7 years, and scores were created to reflect cumulative adversity at 4 developmental periods. At age 7 and 11 years, weight, height, and blood pressure (BP) were measured by clinic staff, and caregivers reported behavior problems. Linear regression was used to estimate associations of cumulative adversity with each outcome (n = 4361) and changes in these outcomes between 7 and 11 years (n = 3348). At age 7 years, mean adversity and chronic exposure to high adversity were associated with elevated body mass index (BMI) and internalizing and externalizing symptoms (P < .05), but not elevated BP. Adversity in all developmental periods was associated with elevated numbers of internalizing and externalizing symptoms (P < .0001), but associations were less robust for BMI. Adversity did not predict change in BMI or BP between age 7 and 11 years, however, it predicted increases in internalizing and externalizing symptoms (P < .0001). Cumulative adversity was associated with BMI and behavior problems at age 7 years, and our data indicate that timing and chronicity of exposure to adversity differentially influence diverse indicators of long-term health risk commonly measured in childhood. This research suggests the hypothesis that interventions to address adversity could reduce the development of multiple chronic disease risk factors and limit their effects on health. Copyright © 2014 Mosby, Inc. All rights reserved.

The Cumulative Effect of Health Adversities on Children's Later Academic Achievement.

PubMed

Quach, Jon; Nguyen, Cattram; O'Connor, Meredith; Wake, Melissa

We aimed to determine whether the accumulation of physical, psychosocial, and combined health adversities measured at age 8 to 9 years predicts worsening of academic scores cross-sectionally at 8 to 9 and longitudinally at 10 to 11 years. Design: Longitudinal data from Waves 3 and 4 in the Longitudinal Study of Australian Children (83% of 4983 retained). Exposures (8-9 years): Physical health adversities (yes/no; summed range, 0-5): overweight, special health care needs, chronic illness, PedsQL Physical, and global health. Psychosocial health adversities (yes/no; summed range, 0-4): parent- and teacher-reported behavior, PedsQL Psychosocial, sleep problems. Combined health adversities (range 0-9). Outcomes (8-9, and 10-11 years): National academic standardized test scores. Generalized estimating equations, accounting for multiple academic domains in each year and socioeconomic position and cognition. At 8 to 9 years, 23.9%, 9.9%, and 5.3% had 1, 2, or ≥3 physical health adversities, respectively, while 27.2%, 9.5%, and 4.9% had 1, 2, or ≥3 psychosocial health adversities. For each additional health adversity at 8 to 9 years, academic scores fell incrementally in year 3 and year 5 (both P < .001), with reductions of at least 0.4 SDs for ≥3 health adversities. Number was more important than type (physical, psychosocial) of adversity. The accumulation of health adversities predicts poorer academic achievement up to 2 years later. Interventions might need to address multiple domains to improve child academic outcomes and be delivered across the health-education interface. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Adverse Drug Reactions in Dental Practice

PubMed Central

Becker, Daniel E.

2014-01-01

Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

Risk prediction in the community: A systematic review of case-finding instruments that predict adverse healthcare outcomes in community-dwelling older adults.

PubMed

O'Caoimh, Rónán; Cornally, Nicola; Weathers, Elizabeth; O'Sullivan, Ronan; Fitzgerald, Carol; Orfila, Francesc; Clarnette, Roger; Paúl, Constança; Molloy, D William

2015-09-01

Few case-finding instruments are available to community healthcare professionals. This review aims to identify short, valid instruments that detect older community-dwellers risk of four adverse outcomes: hospitalisation, functional-decline, institutionalisation and death. Data sources included PubMed and the Cochrane library. Data on outcome measures, patient and instrument characteristics, and trial quality (using the Quality In Prognosis Studies [QUIPS] tool), were double-extracted for derivation-validation studies in community-dwelling older adults (>50 years). Forty-six publications, representing 23 unique instruments, were included. Only five were externally validated. Mean patient age range was 64.2-84.6 years. Most instruments n=18, (78%) were derived in North America from secondary analysis of survey data. The majority n=12, (52%), measured more than one outcome with hospitalisation and the Probability of Repeated Admission score the most studied outcome and instrument respectively. All instruments incorporated multiple predictors. Activities of daily living n=16, (70%), was included most often. Accuracy varied according to instruments and outcomes; area under the curve of 0.60-0.73 for hospitalisation, 0.63-0.78 for functional decline, 0.70-0.74 for institutionalisation and 0.56-0.82 for death. The QUIPS tool showed that 5/23 instruments had low potential for bias across all domains. This review highlights the present need to develop short, reliable, valid instruments to case-find older adults at risk in the community. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Development of Mitral Stenosis After Mitral Valve Repair: Importance of Mitral Valve Area.

PubMed

Chan, Kwan Leung; Chen, Shin-Yee; Mesana, Thierry; Lam, Buu Khanh

2017-12-01

The development of mitral stenosis (MS) is not uncommon after mitral valve (MV) repair for degenerative mitral regurgitation (MR), but the significance of MS in this setting has not been defined. We prospectively studied 110 such patients who underwent supine bicycle exercise testing to assess intracardiac hemodynamics at rest and at peak exercise. B-type natriuretic peptide (BNP) levels were measured at rest and after the exercise test. The patients also performed the 6-minute walk test and completed the 36-Item Short Form Survey (SF-36). Follow-up was performed by a review of the medical record and telephone interview. Of 110 patients, 22 had MS defined by a mitral valve area (MVA) ≤ 1.5 cm 2 . The resting and peak exercise mitral gradients and pulmonary artery systolic pressure were significantly higher in patients with MS compared with patients with an MVA > 1.5 cm 2 . BNP levels at rest and after exercise were also higher in the patients with MS, who also had lower exercise capacity and worse perception of well-being in 3 domains (physical function, vitality, and social function) on the SF-36. MVA had higher specificity and positive predictive value in predicting outcome events compared with a mean gradient of 3 or 5 mm Hg. In patients who had MV repair for degenerative MR, an MVA ≤ 1.5 cm 2 occurs in about one-fifth of patients and is associated with adverse intracardiac hemodynamics, lower exercise capacity, and adverse outcomes. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Predictive modeling of structured electronic health records for adverse drug event detection.

PubMed

Zhao, Jing; Henriksson, Aron; Asker, Lars; Boström, Henrik

2015-01-01

The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and combined. We have demonstrated how machine learning can be applied to electronic health records for the purpose of detecting adverse drug events and proposed solutions to some of the challenges this presents, including how to represent the various data types. Overall, clinical codes are more useful than measurements and, in specific cases, it is beneficial to combine the two.

Predictive modeling of structured electronic health records for adverse drug event detection

PubMed Central

2015-01-01

Background The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Methods Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Results Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and combined. Conclusions We have demonstrated how machine learning can be applied to electronic health records for the purpose of detecting adverse drug events and proposed solutions to some of the challenges this presents, including how to represent the various data types. Overall, clinical codes are more useful than measurements and, in specific cases, it is beneficial to combine the two. PMID:26606038

Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.

PubMed

Zhang, Patrick M; Sarkar, Indra Neil

2018-01-01

Recent technological advancements in genetic testing and the growing accessibility of public genomic data provide researchers with a unique avenue to approach personalized medicine. This feasibility study examined the potential of direct-to-consumer (DTC) genomic tests (focusing on 23andMe) in research and clinical applications. In particular, we combined population genetics information from the Personal Genome Project with adverse event reports from AEOLUS and pharmacogenetic information from PharmGKB. Primarily, associations between drugs based on co-occurring genetic variations and associations between variants and adverse events were used to assess the potential for leveraging single nucleotide polymorphism information from 23andMe. The results of this study suggest potential clinical uses of DTC tests in light of potential drug interactions. Furthermore, the results suggest great potential for analyzing associations at a population level to facilitate knowledge discovery in the realm of predicting adverse drug events.

Increased Trimethylamine N-oxide (TMAO) Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Wilson Tang, W. H.; Wang, Zeneng; Li, Xinmin S.; Fan, Yiying; Li, Daniel S.; Wu, Yuping; Hazen, Stanley L.

2017-01-01

Background Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a pro-atherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. Methods We examined the relationship between fasting TMAO and two of its nutrient precursors, choline and betaine, versus 3-year major adverse cardiac events and 5-year mortality in 1,216 stable patients with T2DM who underwent elective diagnostic coronary angiography. Results TMAO (4.4 µmol/L [interquartile range 2.8–7.7µmol/L] vs. 3.6[2.3–5.7µmol/L]; P<0.001) and choline concentrations were higher in individuals with T2DM versus healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac events risk (P<0.001) and a 3.6-fold increased 5-year mortality risk (P<0.001). Following adjustments for traditional risk factors and high sensitivity C-reactive protein, glycated hemoglobin and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients (e.g. Quartiles 4 vs. 1, hazard ratio 2.05[95%CI 1.31–3.20], P<0.001; and 2.07[95%CI 1.37–3.14], P<0.001, respectively). Conclusion Fasting plasma concentrations of the pro-atherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. PMID:27864387

Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.

PubMed

Tang, W H Wilson; Wang, Zeneng; Li, Xinmin S; Fan, Yiying; Li, Daniel S; Wu, Yuping; Hazen, Stanley L

2017-01-01

Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a proatherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. We examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216 stable patients with T2DM who underwent elective diagnostic coronary angiography. TMAO [4.4 μmol/L (interquartile range 2.8-7.7 μmol/L) vs 3.6 (2.3-5.7 μmol/L); P < 0.001] and choline concentrations were higher in individuals with T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac event risk (P < 0.001) and a 3.6-fold increased 5-year mortality risk (P < 0.001). Following adjustments for traditional risk factors and high-sensitivity C-reactive protein, glycohemoglobin, and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients [e.g., quartiles 4 vs 1, hazard ratio 2.05 (95% CI, 1.31-3.20), P < 0.001; and 2.07 (95% CI, 1.37-3.14), P < 0.001, respectively]. Fasting plasma concentrations of the proatherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. © 2016 American Association for Clinical Chemistry.

Predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical Rockall Score.

PubMed

Tham, T C K; James, C; Kelly, M

2006-11-01

The Rockall risk scoring system uses clinical criteria and endoscopy to identify patients at risk of adverse outcomes after acute upper gastrointestinal haemorrhage. A clinical Rockall score obtained using only the clinical criteria may be able to predict outcome without endoscopy. To validate the clinical Rockall Score in predicting outcome after acute non-variceal upper gastrointestinal haemorrhage. A retrospective observational study of consecutive patients who were admitted with non-variceal acute upper gastrointestinal haemorrhage was undertaken. Medical records were abstracted using a standardised form. 102 cases were identified (51 men and 51 women; mean age 59 years). 38 (37%) patients considered to be at low risk of adverse outcomes (clinical Rockall Score 0) had no adverse outcomes and did not require transfusion. Patients with a clinical Rockall Score of 1-3 had no adverse outcomes, although 13 of 45 (29%) patients required blood transfusions. Clinical Rockall Scores >3 (n = 19) were associated with adverse outcomes (rebleeding in 4 (21%), surgery in 1 (5%) and death in 2 (10%)). The clinical Rockall Score without endoscopy may be a useful prognostic indicator in this cohort of patients with acute non-variceal upper gastrointestinal haemorrhage. This score may reduce the need for urgent endoscopy in low-risk patients, which can instead be carried out on a more elective outpatient basis.

[Spanish versions of the Simplified Motor Score and the Glasgow Coma Scale in out-of-hospital treatment of head injury in adults: a preliminary study of each scale's ability to predict adverse events].

PubMed

Roca, Guillem; Mayol, Sergi; García, Esteban; Casajuana, Edgar; Quintana, Salvador

2015-06-01

To determine the ability of the modified (Spanish) version of the Simplified Motor Score (mSMS) to predict adverse events during hospitalization and to compare its predictive ability to that of the Glasgow Coma Scale (GCS) in adults with head injuries treated outside the hospital. Observational study of retrospective cohorts including all patients over the age of 14 years attended for head injuries occurring within 24 hours of treatment by an advanced life-support unit staffed by nurses between May 1, 2013, and May 1, 2014. The mSMS was a translation of the English original, created through a process of discussions of direct and back translations to arrive at consensus. Out-of-hospital patient records were searched to find GCS and mSMS scores. To predict the ability of each scale to predict brain injuries, neurosurgery, intubation, and/or inhospital death, we calculated the area under the receiving operator characteristic curves (AUCs). Of the total of 115 head-injury patients attended, 64 met the inclusion criteria. The mean (SD) age was 47 (24) years. Twelve (18.8%) patients developed some form of adverse event during hospitalization; 91.6% had brain damage, 58.3% required intubation, 8.3% required surgery, and 41.6% died. The AUC for the GCS was 0.907 (95% CI, 0.81-1.00; P<.001); the AUC for the mSMS was 0.796 (95% CI, 0.64-0.95; P=.001). Although the ability of the mSMS to predict in-hospital adverse outcomes is good, it is inferior to the GCS in adults with head injuries attended outside the hospital.

The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem.

PubMed

Yen, Cheng-Fang; Yang, Pinchen; Wu, Yu-Yu; Cheng, Chung-Ping

2013-11-01

This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.

The evolution of predictive adaptive responses in human life history

PubMed Central

Nettle, Daniel; Frankenhuis, Willem E.; Rickard, Ian J.

2013-01-01

Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a ‘weather forecast’ of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state. PMID:23843395

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries

PubMed Central

Lev-Ran, Shaul

2017-01-01

Background Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Objective Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. Methods We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration’s Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Results Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). Conclusions These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. PMID:29074469

Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

PubMed

Azab, Basem; Daoud, Jacques; Naeem, Fahad Ben; Nasr, Rabih; Ross, Jennifer; Ghimire, Pratima; Siddiqui, Ayesha; Azzi, Nadine; Rihana, Nancy; Abdallah, Marie; Azzi, Nassif; Patel, Parishram; Kleiner, Morton; El-Sayegh, Suzanne

2012-01-01

Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

Effects of war exposure on Air Force personnel’s mental health, job burnout and other organizational related outcomes

PubMed Central

Vinokur, Amiram D.; Pierce, Penny F.; Lewandowski-Romps, Lisa; Hobfoll, Stevan E.; Galea, Sandro

2011-01-01

Longitudinal data from a stratified representative sample of U.S. Air Force personnel (N = 1009) deployed to the wars in Iraq, Afghanistan, and other locations were analyzed in this study. Using structural equation models, we examined the effects of war exposure on traumatic experiences, Post Traumatic Stress (PTS) symptoms, resource loss, and on subsequent functioning, perceived health, and on job and organizationally relevant outcomes. The job and organizational outcomes included job burnout, job involvement, job strain, job satisfaction, work-family conflict, organizational commitment, deployment readiness, and intention to reenlist. We found that deployment to the theater of the war increased risk of exposure to trauma, which in turn, predicted elevated PTS symptoms and resource loss. PTS symptoms predicted later loss of resources and deterioration in perceived health and functioning. In turn, resource loss predicted negative job and organizational outcomes. Exposure to trauma fully mediated the effects of deployment to the theater of war on PTS symptoms and resource loss and had additional significant indirect effects on several job and organizational relevant outcomes. For returning veterans, deployment to the theater of war, exposure to trauma, PTS symptoms, and resource loss represents a ‘cascading’ chain of events that over time results in a decline of health and functioning as well as in adverse job and organizationally relevant outcomes that may affect organizational effectiveness. PMID:21280941

The added predictive value of biphasic events in ST analysis of the fetal electrocardiogram for intrapartum fetal monitoring.

PubMed

Becker, Jeroen H; Krikhaar, Anniek; Schuit, Ewoud; Mårtendal, Annika; Maršál, Karel; Kwee, Anneke; Visser, Gerard H A; Amer-Wåhlin, Isis

2015-02-01

To study the predictive value of biphasic ST-events for interventions for suspected fetal distress and adverse neonatal outcome, when using ST-analysis of the fetal electrocardiogram (FECG) for intrapartum fetal monitoring. Prospective cohort study. Three academic hospitals in Sweden. Women in labor with a high-risk singleton fetus in cephalic position beyond 36 weeks of gestation. In women in labor who were monitored with conventional cardiotocography, ST-waveform analysis was recorded and concealed. Traces with biphasic ST-events of the FECG (index) were compared with traces without biphasic events of the FECG. The ability of biphasic events to predict interventions for suspected fetal distress and adverse outcome was assessed using univariable and multivariable logistic regression analyses. Interventions for suspected fetal distress and adverse outcome (defined as presence of metabolic acidosis (i.e. umbilical cord pH <7.05 and base deficit in extracellular fluid >12 mmol), umbilical cord pH <7.00, 5-min Apgar score <7, admittance to neonatal intensive care unit or perinatal death). Although the presence of biphasic events of the FECG was associated with more interventions for fetal distress and an increased risk of adverse outcome compared with cases with no biphasic events, the presence of significant (i.e. intervention advised according to cardiotocography interpretation) biphasic events showed no independent association with interventions for fetal distress [odds ratio (OR) 1.71, 95% confidence interval (CI) 0.65-4.50] or adverse outcome (OR 1.96, 95% CI 0.74-5.24). The presence of significant biphasic events did not discriminate in the prediction of interventions for fetal distress or adverse outcome. Therefore, biphasic events in relation to ST-analysis monitoring during birth should be omitted if future studies confirm our findings. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

PubMed

Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

2015-01-01

A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency, malnutrition, pressure sore risk, and self-rated health. None of these risk factors significantly increased the risk of adverse outcome (LR+ range = 0.78 to 2.84). The absence of dependency reduces the risk of 1-year mortality (LR- = 0.27) and nursing home placement (LR- = 0.27). Five constructs of frailty were evaluated, but none increased or decreased the risk of adverse outcome. Three instruments were evaluated in the meta-analysis: Identification of Seniors at Risk, Triage Risk Screening Tool, and Variables Indicative of Placement Risk. None of these instruments significantly increased (LR+ range for various outcomes = 0.98 to 1.40) or decreased (LR- range = 0.53 to 1.11) the risk of adverse outcomes. The test threshold for 3-month functional decline based on the most accurate instrument was 42%, and the treatment threshold was 61%. Risk stratification of geriatric adults following ED care is limited by the lack of pragmatic, accurate, and reliable instruments. Although absence of dependency reduces the risk of 1-year mortality, no individual risk factor, frailty construct, or risk assessment instrument accurately predicts risk of adverse outcomes in older ED patients. Existing instruments designed to risk stratify older ED patients do not accurately distinguish high- or low-risk subsets. Clinicians, educators, and policy-makers should not use these instruments as valid predictors of post-ED adverse outcomes. Future research to derive and validate feasible ED instruments to distinguish vulnerable elders should employ published decision instrument methods and examine the contributions of alternative variables, such as health literacy and dementia, which often remain clinically occult. © 2014 by the Society for Academic Emergency Medicine.

Framework for computationally-predicted AOPs

EPA Science Inventory

Framework for computationally-predicted AOPs Given that there are a vast number of existing and new chemicals in the commercial pipeline, emphasis is placed on developing high throughput screening (HTS) methods for hazard prediction. Adverse Outcome Pathways (AOPs) represent a...

Overview of an internationally-harmonized program for adverse outcome pathway development

EPA Science Inventory

Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

Indoor NO2 air pollution and lung function of professional cooks.

PubMed

Arbex, M A; Martins, L C; Pereira, L A A; Negrini, F; Cardoso, A A; Melchert, W R; Arbex, R F; Saldiva, P H N; Zanobetti, A; Braga, A L F

2007-04-01

Studies of cooking-generated NO2 effects are rare in occupational epidemiology. In the present study, we evaluated the lung function of professional cooks exposed to NO2 in hospital kitchens. We performed spirometry in 37 cooks working in four hospital kitchens and estimated the predicted FVC, FEV1 and FEF(25-75), based on age, sex, race, weight, and height, according to Knudson standards. NO2 measurements were obtained for 4 consecutive days during 4 different periods at 20-day intervals in each kitchen. Measurements were performed inside and outside the kitchens, simultaneously using Palm diffusion tubes. A time/exposure indicator was defined as representative of the cumulative exposure of each cook. No statistically significant effect of NO2 exposure on FVC was found. Each year of work as a cook corresponded to a decrease in predicted FEV1 of 2.5% (P = 0.046) for the group as a whole. When smoking status and asthma were included in the analysis the effect of time/exposure decreased about 10% and lost statistical significance. On predicted FEF(25-75), a decrease of 3.5% (P = 0.035) was observed for the same group and the inclusion of controllers for smoking status and asthma did not affect the effects of time/exposure on pulmonary function parameter. After a 10-year period of work as cooks the participants of the study may present decreases in both predicted FEV1 and FEF(25-75) that can reach 20 and 30%, respectively. The present study showed small but statistically significant adverse effects of gas stove exposure on the lung function of professional cooks.

Adult Attachment Interview Discourse Patterns Predict Metabolic Syndrome in Midlife

PubMed Central

Davis, Cynthia R.; Usher, Nicole; Dearing, Eric; Barkai, Ayelet R.; Crowell-Doom, Cindy; Mantzoros, Christos S.; Crowell, Judith A.

2017-01-01

Objective Adult attachment discourse patterns and current family relationship quality were examined as predictors of health behaviors and number of Metabolic Syndrome (MetS) criteria met. Methods A sample of 215 White/European American and Black/African American adults, aged 35 to 55, were examined cross-sectionally. Discourse was assessed with the Adult Attachment Interview (AAI), specifically: 1) coherence, a marker of attachment security, 2) unresolved trauma/loss, a marker of disorganized and distorted cognition related to trauma, and 3) idealization, the tendency to minimize the impact of stressful experiences. Health behaviors of diet, exercise, smoking and alcohol use were also assessed, as were adverse childhood experiences, current depressive symptoms and relationship functioning. MetS includes hypertension, hyperglycemia, high triglycerides, low HDL cholesterol, and obesity. Results Using path analysis and accounting for childhood adversity and depressive symptoms, AAI coherence and unresolved trauma or loss were directly linked to number of MetS criteria met (β = −.22 and .21 respectively). Idealization was indirectly linked to MetS through poor diet (β = −.26 and −.36 respectively), predicting 21% of the variance in number of MetS criteria met. Conclusions Attachment representations related to stress appraisal and care-seeking behaviors appear to serve as cognitive mechanisms increasing risk of MetS. PMID:25264975

Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism.

PubMed

Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

2016-05-20

Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.

Trajectories of depressive symptoms in foster youth transitioning into adulthood: the roles of emotion dysregulation and PTSD.

PubMed

Valdez, Christine E; Bailey, Brenda E; Santuzzi, Alecia M; Lilly, Michelle M

2014-01-01

Foster youth often experience considerable adversity both in and out of foster care, including histories of abuse and/or neglect, and further stressors within the foster system. These adverse experiences often occur at key developmental periods that can compromise emotional functioning and lead to posttraumatic symptomatology, including posttraumatic stress disorder (PTSD) and emotion dysregulation. In the face of difficult histories and ongoing mental health challenges, youth transitioning into adulthood may be particularly vulnerable to increases in depressive symptoms. We explored the trajectory of depressive symptoms in foster youth from age 17 to 19 using a piecewise linear growth model, examining the effects of PTSD and emotion dysregulation on youth's depressive symptoms over time. Results revealed depressive symptoms decreased from age 17 to 18 but increased from 18 to 19. PTSD and emotion dysregulation predicted greater baseline depressive symptoms and decreases in symptoms from age 17 to 18, whereas only PTSD predicted increases in depressive symptoms from 18 to 19. Females reported higher levels of depressive symptoms compared to males. Additionally, emotion dysregulation was a stronger predictor of depressive symptoms for females than males. Implications for service delivery for foster youth transitioning into adulthood are discussed. © The Author(s) 2014.

Small-for-gestational age and large-for-gestational age thresholds to predict infants at risk of adverse delivery and neonatal outcomes: are current charts adequate? An observational study from the Born in Bradford cohort

PubMed Central

Norris, T; Johnson, W; Farrar, D; Tuffnell, D; Wright, J; Cameron, N

2015-01-01

Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinically recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age (SGA: birth weight <10th centile) and large-for-gestational age (LGA: birth weight >90th centile). Design Prospective cohort study. Setting Born in Bradford (BiB) study, UK. Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age, birth weight, ethnicity, maternal height, weight and parity. Main outcome measures Prevalence of SGA and LGA, using the three charts and indicators of diagnostic utility (sensitivity, specificity and area under the receiver operating characteristic (AUROC)) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome. Results In White British and Pakistani infants, the prevalence of SGA and LGA differed depending on the chart used. Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart, while the opposite was apparent when classifying LGA infants. However, the predictive utility of all three charts to identify adverse clinical outcomes was poor, with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts. Conclusions Despite being recommended in national clinical guidelines, the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes. Being small or large may increase the risk of an adverse outcome; however, size alone is not sensitive or specific enough with current detection to be useful. However, a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations. PMID:25783424

PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome.

PubMed

George, Joanne M; Boyd, Roslyn N; Colditz, Paul B; Rose, Stephen E; Pannek, Kerstin; Fripp, Jurgen; Lingwood, Barbara E; Lai, Melissa M; Kong, Annice H T; Ware, Robert S; Coulthard, Alan; Finn, Christine M; Bandaranayake, Sasaka E

2015-09-16

More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay). Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes. Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013.

Biodiversity, ecosystem functions and services in environmental risk assessment: introduction to the special issue.

PubMed

Schäfer, Ralf B

2012-01-15

This Special Issue focuses on the questions if and how biodiversity, ecosystem functions and resulting services could be incorporated into the Ecological Risk Assessment (ERA). Therefore, three articles provide a framework for the integration of ecosystem services into ERA of soils, sediments and pesticides. Further articles demonstrate ways how stakeholders can be integrated into an ecosystem service-based ERA for soils and describe how the current monitoring could be adapted to new assessment endpoints that are directly linked to ecosystem services. Case studies show that the current ERA may not be protective for biodiversity, ecosystem functions and resulting services and that both pesticides and salinity currently adversely affect ecosystem functions in the field. Moreover, ecological models can be used for prediction of new protection goals and could finally support their implementation into the ERA. Overall, the Special Issue stresses the urgent need to enhance current procedures of ERA if biodiversity, ecosystem functions and resulting services are to be protected. Copyright © 2011 Elsevier B.V. All rights reserved.

Respiratory Sinus Arrhythmia Activity Predicts Internalizing and Externalizing Behaviors in Non-referred Boys

PubMed Central

Zhang, Wei; Fagan, Shawn E.; Gao, Yu

2017-01-01

Atypical respiratory sinus arrhythmia (RSA), a biomarker of emotion dysregulation, is associated with both externalizing and internalizing behaviors. In addition, social adversity and gender may moderate this association. In this study, we investigated if RSA (both resting RSA and RSA reactivity in an emotion regulation task) predicts externalizing and/or internalizing behaviors and the extent to which social adversity moderates this relationship. Two hundred and fifty-three children (at Time 1, mean age = 9.05, SD = 0.60, 48% boys) and their caregivers from the community participated in this study. Resting RSA and RSA reactivity were assessed, and caregivers reported children’s externalizing and internalizing behaviors at both Time 1 and Time 2 (1 year later). We found that lower resting RSA (but not RSA reactivity) at Time 1 was associated with increased externalizing and internalizing behaviors at Time 2 in boys, even after controlling for the effects of Time 1 behavioral problems and Time 2 age. Moreover, there was a significant interaction effect between Time 1 resting RSA and social adversity such that lower resting RSA predicted higher externalizing and internalizing behaviors in boys only under conditions of high social adversity. Follow-up analyses revealed that these predictive effects were stronger for externalizing behavior than for internalizing behavior. No significant effects were found for girls. Our findings provide further evidence that low resting RSA may be a transdiagnostic biomarker of emotion dysregulation and a predisposing risk factor for both types of behavior problems, in particular for boys who grow up in adverse environments. We conclude that biosocial interaction effects and gender differences should be considered when examining the etiological mechanisms of child psychopathology. PMID:28955262

The interaction between temperament and the family environment in adolescent substance use and externalizing behaviors: Support for diathesis–stress or differential susceptibility?

PubMed Central

Rioux, Charlie; Castellanos-Ryan, Natalie; Parent, Sophie; Séguin, Jean R.

2016-01-01

Both individual and environmental factors predict externalizing behaviors and substance use (EB-SU); however, different patterns of interaction among these factors may have different implications. This review first examines how temperament and the family environment interact in the prediction of adolescent EB-SU. Second, studies are reviewed according to two theoretical models: (1) diathesis–stress, i.e., certain individual characteristics are linked to vulnerability and later problems in adverse environments; (2) differential susceptibility, i.e., these characteristics are linked to susceptibility, predicting problems in adverse environments, but also better than average outcomes in good environments. Fourteen studies focusing on the prediction of EB-SU at ages 12–18 were selected through a literature search. Results showed that certain temperament traits (high levels of impulsivity and disinhibition; low levels of effortful control, negative affect, fearfulness and shyness), hereby designated as “adventurous” disposition, were associated with higher levels of EB-SU in adverse family environments. Some studies also showed that children with “adventurous” temperament traits in positive environments had the lowest levels of EB-SU. This suggests that prevention of EB-SU might target family factors such as parenting and focus on children with “adventurous” temperament traits. Further, studies that supported the differential susceptibility model were those assessing temperament and the family environment in childhood and studies that supported the diathesis–stress model assessed these variables in adolescence. It is thus possible that some of these “adventurous” temperament traits, with regard to EB-SU, would be indicators of susceptibility to both enriched and adverse environments in childhood but no longer in adolescence, when they would only be indicators of vulnerability to adverse environments. PMID:27413247

Development of a Fragment-Based in Silico Profiler for Michael Addition Thiol Reactivity.

PubMed

Ebbrell, David J; Madden, Judith C; Cronin, Mark T D; Schultz, Terry W; Enoch, Steven J

2016-06-20

The Adverse Outcome Pathway (AOP) paradigm details the existing knowledge that links the initial interaction between a chemical and a biological system, termed the molecular initiating event (MIE), through a series of intermediate events, to an adverse effect. An important example of a well-defined MIE is the formation of a covalent bond between a biological nucleophile and an electrophilic compound. This particular MIE has been associated with various toxicological end points such as acute aquatic toxicity, skin sensitization, and respiratory sensitization. This study has investigated the calculated parameters that are required to predict the rate of chemical bond formation (reactivity) of a dataset of Michael acceptors. Reactivity of these compounds toward glutathione was predicted using a combination of a calculated activation energy value (Eact, calculated using density functional theory (DFT) calculation at the B3YLP/6-31G+(d) level of theory, and solvent-accessible surface area values (SAS) at the α carbon. To further develop the method, a fragment-based algorithm was developed enabling the reactivity to be predicted for Michael acceptors without the need to perform the time-consuming DFT calculations. Results showed the developed fragment method was successful in predicting the reactivity of the Michael acceptors excluding two sets of chemicals: volatile esters with an extended substituent at the β-carbon and chemicals containing a conjugated benzene ring as part of the polarizing group. Additionally the study also demonstrated the ease with which the approach can be extended to other chemical classes by the calculation of additional fragments and their associated Eact and SAS values. The resulting method is likely to be of use in regulatory toxicology tools where an understanding of covalent bond formation as a potential MIE is important within the AOP paradigm.

The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.

PubMed

Callaghan, Bridget L; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

2014-12-01

Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. © 2014 Wiley Periodicals, Inc.

Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role.

PubMed

Zar-Kessler, Claire A M; Belkind-Gerson, Jaime; Bender, Suzanne; Kuo, Braden M

2017-07-01

Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

Metagenomics approach to the study of the gut microbiome structure and function in zebrafish Danio rerio fed with gluten formulated diet.

PubMed

Koo, Hyunmin; Hakim, Joseph A; Powell, Mickie L; Kumar, Ranjit; Eipers, Peter G; Morrow, Casey D; Crowley, Michael; Lefkowitz, Elliot J; Watts, Stephen A; Bej, Asim K

2017-04-01

In this study, we report the gut microbial composition and predictive functional profiles of zebrafish, Danio rerio, fed with a control formulated diet (CFD), and a gluten formulated diet (GFD) using a metagenomics approach and bioinformatics tools. The microbial communities of the GFD-fed D. rerio displayed heightened abundances of Legionellales, Rhizobiaceae, and Rhodobacter, as compared to the CFD-fed counterparts. Predicted metagenomics of microbial communities (PICRUSt) in GFD-fed D. rerio showed KEGG functional categories corresponding to bile secretion, secondary bile acid biosynthesis, and the metabolism of glycine, serine, and threonine. The CFD-fed D. rerio exhibited KEGG functional categories of bacteria-mediated cobalamin biosynthesis, which was supported by the presence of cobalamin synthesizers such as Bacteroides and Lactobacillus. Though these bacteria were absent in GFD-fed D. rerio, a comparable level of the cobalamin biosynthesis KEGG functional category was observed, which could be contributed by the compensatory enrichment of Cetobacterium. Based on these results, we conclude D. rerio to be a suitable alternative animal model for the use of a targeted metagenomics approach along with bioinformatics tools to further investigate the relationship between the gluten diet and microbiome profile in the gut ecosystem leading to gastrointestinal diseases and other undesired adverse health effects. Copyright © 2017. Published by Elsevier B.V.

Large-scale exploration and analysis of drug combinations.

PubMed

Li, Peng; Huang, Chao; Fu, Yingxue; Wang, Jinan; Wu, Ziyin; Ru, Jinlong; Zheng, Chunli; Guo, Zihu; Chen, Xuetong; Zhou, Wei; Zhang, Wenjuan; Li, Yan; Chen, Jianxin; Lu, Aiping; Wang, Yonghua

2015-06-15

Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered. We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications. The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long term effects of early adversity on cognitive function.

PubMed

Richards, M; Wadsworth, M E J

2004-10-01

To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

Experimental Approaches to Systematic Discovery and Development of Reproductive Adverse Outcome Pathways in Fish

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...

Adverse outcome pathways (AOPs): A framework to support predictive toxicology

EPA Science Inventory

High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

Identifying Childhood Characteristics that Underlie Pre-Morbid Risk for Substance Use Disorders: Socialization and Boldness

PubMed Central

Hicks, Brian M.; Iacono, William G.; McGue, Matt

2013-01-01

Utilizing a longitudinal twin study (N = 2510), we identified the child characteristics present prior to initiation of substance use that best predicted later substance use disorders. Two independent traits accounted for the majority of pre-morbid risk: socialization (conformity to rules and conventional values) and boldness (sociability and social assurance, stress resilience, and thrill seeking). Low socialization was associated with disruptive behavior disorders, parental externalizing disorders, and environmental adversity, and exhibited moderate genetic (.45) and shared environmental influences (.30). Boldness was highly heritable (.71) and associated with less internalizing distress and environmental adversity. Together, these traits exhibited robust associations with adolescent and young adult substance use disorders (R = .48 and .50, respectively), and incremental prediction over disruptive behavior disorders, parental externalizing disorders, and environmental adversity. Results were replicated in an independent sample. Socialization and boldness offer a novel conceptualization of underlying risk for substance use disorders that has the potential to improve prediction and theory with implications for basic research, prevention, and intervention. PMID:24280373

Identifying childhood characteristics that underlie premorbid risk for substance use disorders: socialization and boldness.

PubMed

Hicks, Brian M; Iacono, William G; McGue, Matt

2014-02-01

We utilized a longitudinal twin study (N = 2,510) to identify the child characteristics present prior to initiation of substance use that best predicted later substance use disorders. Two independent traits accounted for the majority of premorbid risk: socialization (conformity to rules and conventional values) and boldness (sociability and social assurance, stress resilience, and thrill seeking). Low socialization was associated with disruptive behavior disorders, parental externalizing disorders, and environmental adversity and exhibited moderate genetic (0.45) and shared environmental influences (0.30). Boldness was highly heritable (0.71) and associated with less internalizing distress and environmental adversity. In combination, these traits exhibited robust associations with adolescent and young adult substance use disorders (R = .48 and .50, respectively) and incremental prediction over disruptive behavior disorders, parental externalizing disorders, and environmental adversity. The results were replicated in an independent sample. Socialization and boldness offer a novel conceptualization of underlying risk for substance use disorders that has the potential to improve prediction and theory with implications for basic research, prevention, and intervention.

Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in Theater and Visuospatial Function in Gulf War Veterans.

PubMed

Chao, Linda L

2016-10-01

The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans. The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses. The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans' brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia.

Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.

PubMed

Claes, E; Evers-Kiebooms, G; Denayer, L; Decruyenaere, M; Boogaerts, A; Philippe, K; Legius, E

2005-10-01

This prospective study evaluates emotional functioning and illness representations in 68 unaffected women (34 carriers/34 noncarriers) 1 year after predictive testing for BRCA1/2 mutations when offered within a multidisciplinary approach. Carriers had higher subjective risk perception of breast cancer than noncarriers. Carriers who did not have prophylactic oophorectomy had the highest risk perception of ovarian cancer. No differences were found between carriers and noncarriers regarding perceived seriousness and perceived control of breast and ovarian cancer. Mean levels of distress were within normal ranges. Only few women showed an overall pattern of clinically elevated distress. Cancer-specific distress and state-anxiety significantly decreased in noncarriers from pre- to posttest while general distress remained about the same. There were no significant changes in distress in the group of carriers except for ovarian cancer distress which significantly decreased from pre- to posttest. Our study did not reveal adverse effects of predictive testing when offered in the context of a multidisciplinary approach.

Developmental telomere attrition predicts impulsive decision-making in adult starlings

PubMed Central

Bateson, Melissa; Brilot, Ben O.; Gillespie, Robert; Monaghan, Pat; Nettle, Daniel

2015-01-01

Animals in a poor biological state face reduced life expectancy, and as a consequence should make decisions that prioritize immediate survival and reproduction over long-term benefits. We tested the prediction that if, as has been suggested, developmental telomere attrition is a biomarker of state and future life expectancy, then individuals who have undergone greater developmental telomere attrition should display greater choice impulsivity as adults. We measured impulsive decision-making in a cohort of European starlings (Sturnus vulgaris) in which we had previously manipulated developmental telomere attrition by cross-fostering sibling chicks into broods of different sizes. We show that as predicted by state-dependent optimality models, individuals who had sustained greater developmental telomere attrition and who had shorter current telomeres made more impulsive foraging decisions as adults, valuing smaller, sooner food rewards more highly than birds with less attrition and longer telomeres. Our findings shed light on the biological embedding of early adversity and support a functional explanation for its consequences that could be applicable to other species, including humans. PMID:25473012

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

PubMed

Grodin, Justin L; Mullens, Wilfried; Dupont, Matthias; Wu, Yuping; Taylor, David O; Starling, Randall C; Tang, W H Wilson

2015-07-01

Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Childhood adversity and cognitive function in schizophrenia spectrum disorders and healthy controls: evidence for an association between neglect and social cognition.

PubMed

Kilian, S; Asmal, L; Chiliza, B; Olivier, M R; Phahladira, L; Scheffler, F; Seedat, S; Marder, S R; Green, M F; Emsley, R

2017-12-22

Childhood adversity is associated with cognitive impairments in schizophrenia. However, findings to date are inconsistent and little is known about the relationship between social cognition and childhood trauma. We investigated the relationship between childhood abuse and neglect and cognitive function in patients with a first-episode of schizophrenia or schizophreniform disorder (n = 56) and matched healthy controls (n = 52). To the best of our knowledge, this is the first study assessing this relationship in patients and controls exposed to similarly high levels of trauma. Pearson correlational coefficients were used to assess correlations between Childhood Trauma Questionnaire abuse and neglect scores and cognition. For the MCCB domains displaying significant (p < 0.05) correlations, within group hierarchical linear regression, was done to assess whether abuse and neglect were significant predictors of cognition after controlling for the effect of education. Patients and controls reported similarly high levels of abuse and neglect. Cognitive performance was poorer for patients compared with controls for all cognitive domains except working memory and social cognition. After controlling for education, exposure to childhood neglect remained a significant predictor of impairment in social cognition in both patients and controls. Neglect was also a significant predictor of poorer verbal learning in patients and of attention/vigilance in controls. However, childhood abuse did not significantly predict cognitive impairments in either patients or controls. These findings are cross sectional and do not infer causality. Nonetheless, they indicate that associations between one type of childhood adversity (i.e. neglect) and social cognition are present and are not illness-specific.

[Predictive value of qualitative assessment of general movements for adverse outcomes at 24 months of age in infants with asphyxia].

PubMed

Chen, Nan; Wen, Xiao-Hong; Huang, Jin-Hua; Wang, Shui-Yun; Zhu, Yue-E

2015-12-01

To investigate the predictive value of the qualitative assessment of general movements (GMs) for adverse outcomes at 24 months of age in full-term infants with asphyxia. A total of 114 full-term asphyxiated infants, who were admitted to the neonatal intensive care unit between 2009 and 2012 and took part in follow-ups after discharge were included in the study. All of them received the qualitative assessment of GMs within 3 months after birth. The development quotient was determined with the Bayley Scales of Infant Development at 24 months of age. The results of the qualitative assessment of GMs within 3 months after birth showed that among 114 infants, 20 (17.5%) had poor repertoire movements and 7 (6.1%) had cramped-synchronized movements during the writhing movements period; 8 infants (7.0%) had the absence of fidgety movements during the fidgety movements period. The results of development quotient at 24 months of age showed that 7 infants (6.1%) had adverse developmental outcomes: 6 cases of cerebral palsy and mental retardation and 1 case of mental retardation. There was a poor consistency between poor repertoire movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=-0.019; P>0.05). There was a high consistency between cramped-synchronized movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=0.848; P<0.05), and the results of predictive values of cramped-synchronized movements were shown as follows: predictive validity 98.2%, sensitivity 85.7%, specificity 99.1%, positive predictive value 85.7%, and negative predictive value 99.1%. There was a high consistency between the absence of fidgety movements during the fidgety movements period and the developmental outcomes at 24 months of age (Kappa=0.786; P<0.05), and its predictive values were expressed as follows: predictive validity 97.4%, sensitivity 85.7%, specificity 98.1%, positive predictive value 75.0%, and negative predictive value 99.1%. Cramped-synchronized movements and absence of fidgety movements can predict adverse developmental outcomes at 24 months of age in full-term infants with asphyxia.

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries.

PubMed

Yom-Tov, Elad; Lev-Ran, Shaul

2017-10-26

Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R 2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. ©Elad Yom-Tov, Shaul Lev-Ran. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.10.2017.

Pathways between childhood/adolescent adversity, adolescent socioeconomic status, and long-term cardiovascular disease risk in young adulthood.

PubMed

Doom, Jenalee R; Mason, Susan M; Suglia, Shakira F; Clark, Cari Jo

2017-09-01

The current study investigated mediators between childhood/adolescent adversities (e.g., dating violence, maltreatment, homelessness, and parental death), low socioeconomic status (SES) during adolescence, and cardiovascular disease (CVD) risk in young adulthood. The purpose of these analyses was to understand whether SES during adolescence and childhood/adolescent adversities affect CVD risk through similar pathways, including maternal relationship quality, health behaviors, financial stress, medical/dental care, educational attainment, sleep problems, and depressive symptoms. Using the National Longitudinal Study of Adolescent to Adult Health (N = 14,493), which has followed US adolescents (Wave 1; M = 15.9 years) through early adulthood (Wave 4; M = 28.9 years), associations were examined between childhood/adolescent adversity and SES to 30-year CVD risk in young adulthood. The outcome was a Framingham-based prediction model of CVD risk that included age, sex, body mass index, smoking, systolic blood pressure, diabetes, and antihypertensive medication use at Wave 4. Path analysis was used to examine paths through the adolescent maternal relationship to young adult mediators of CVD risk. Childhood/adolescent adversity significantly predicted greater adult CVD risk through the following pathways: maternal relationship, health behaviors, financial stress, lack of medical/dental care, and educational attainment; but not through depressive symptoms or sleep problems. Lower SES during adolescence significantly predicted greater adult CVD risk through the following pathways: health behaviors, financial stress, lack of medical/dental care, and educational attainment, but not maternal relationship, depressive symptoms, or sleep problems. Childhood/adolescent adversities and SES affected CVD risk in young adulthood through both similar and unique pathways that may inform interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Usefulness of Myocardial Annular Velocity Change During Mental Stress to Predict Cardiovascular Outcome in Patients With Coronary Artery Disease (From the Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram Treatment Trial).

PubMed

Alenezi, Fawaz; Brummett, Beverly H; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Alzaeim, Nabil; Wilson, Jennifer; Romano, Minna M D; Sun, Julia L; Ersboll, Mads; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

2017-11-01

Mental stress-induced myocardial ischemia is common and a prognostic factor of adverse cardiovascular outcomes in patients with coronary artery disease (CAD). The present study aimed at examining associations between mental stress-induced myocardial annular velocity (MAV) and cardiovascular outcome in patients with CAD. MAV, specifically, diastolic early (e'), diastolic late (a'), and systolic (s') velocities were obtained at rest and during mental stress testing in 224 patients with clinically stable CAD. Using Cox regression models, age, sex, and baseline-adjusted mental stress-induced MAV measures were examined as predictors of a priori defined composite event term that comprised all-cause mortality and/or nonfatal cardiovascular events, resulting in an unplanned hospitalization (major adverse cardiovascular events [MACE]). Median follow-up was 4 years. The sample was predominantly male, Caucasian with New York Heart Association functional class I and a mean age of 63 ± 10.2 years. MS-induced changes in e' (hazard ratio [HR] = .73) and s' (HR = .73) were significant (p <0.05) predictors of MACE, and the change in a' (HR = .74) was marginal (p = 0.05). The pattern of the relation for each MAV measure was such that patients with a greater decrease in e' and/or s' velocity had a higher probability of experiencing an MACE, and the association of the change in a' and MACE was marginal (p = 0.05), but the same tendency. The associations between MS-induced values of e' and a' for MACE were independent of resting levels. Mental stress-induced MAV changes independently predict an adverse cardiovascular outcome in patients with stable CAD. Copyright © 2017 Elsevier Inc. All rights reserved.

Age, overtime, and employee health, safety and productivity outcomes: a case study.

PubMed

Allen, Harris; Woock, Christopher; Barrington, Linda; Bunn, William

2008-08-01

To expand a study of the impact of overtime on employee health, safety, and productivity outcomes, previously reported in this journal, with tests comparing older versus younger workers on these relationships. Secondary analyses of a longitudinal panel (n = 2746) representing workers at US sites for a heavy manufacturer during 2001 to 2002. Structural equation techniques were used to assess two hypotheses in the context of multiple group models positing the prediction of a broad set of employee outcomes using a three-step causal sequence. One set of models compared overtime impact for three age groups (<45, 45 to 49, 50+) at the aggregate level. Two others compared overtime impact for the three age groups by compensation type (hourly vs salaried). Advancing age was linked to greater rates of adverse consequences as a function of overtime (hypothesis #1), but these increases were largely confined to hourly employees working extended overtime (averaging 60+ hours per week) and occurred on only four of the nine study outcomes. With respect to moderate overtime (48.01 to 59.99 hours) and to variables reflecting the possible impact of past overtime (eg, prior disability episodes), increases in age among hourly employees did not lead to stronger associations between overtime and adverse outcomes on most tests and in fact in many cases were linked to decrements in these associations (hypothesis #2). Salaried employees recorded no greater linkages between overtime and adverse outcomes with advancing age across all tests involving hypothesized overtime effects or "possibly a function of overtime" effects. The results support the proposition that, when employees work overtime, adverse outcomes--and indirect costs--do not increase with advancing age in any kind of wholesale fashion. Where rates of adverse outcomes do increase, they are confined to certain subgroups of employees doing certain types of work and occur on certain dimensions at certain levels of longer work hours. It is argued that carefully calibrated approaches vis-à-vis older workers are needed to maximize employer capacity to address the unique challenges posed by this increasingly important portion of the workforce.

Chains of risk for alcohol use disorder: Mediators of exposure to neighborhood deprivation in early and middle childhood.

PubMed

Karriker-Jaffe, Katherine J; Lönn, Sara L; Cook, Won K; Kendler, Kenneth S; Sundquist, Kristina

2018-03-01

Our goal was to test a cascade model to identify developmental pathways, or chains of risk, from neighborhood deprivation in childhood to alcohol use disorder (AUD) in young adulthood. Using Swedish general population data, we examined whether exposure to neighborhood deprivation during early and middle childhood was associated with indicators of social functioning in adolescence and emerging adulthood, and whether these were predictive of AUD. Structural equation models showed exposure to neighborhood deprivation was associated with lower school achievement during adolescence, poor social functioning during emerging adulthood, and the development of AUD for both males and females. Understanding longitudinal pathways from early exposure to adverse environments to later AUD can inform prevention and intervention efforts. Copyright © 2018 Elsevier Ltd. All rights reserved.

Negative Emotionality and Disconstraint Influence PTSD Symptom Course via Exposure to New Major Adverse Life Events

PubMed Central

Sadeh, Naomi; Miller, Mark W.; Wolf, Erika J.; Harkness, Kate L.

2015-01-01

Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23 – 68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality over time. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events. PMID:25659969

Bovine thrombin safety reporting: an example of study design and publication bias.

PubMed

Crean, Sheila; Michels, Shannon L; Moschella, Kevin; Reynolds, Matthew W

2010-01-01

Bovine thrombin, a popular hemostat and sealant since 1945, has recently been subjected to clinical trial testing due to reformulations in 1998. We sought to compare adverse event rates of early observational studies with those of later interventional trials. A MEDLINE-based literature search in publications that report safety in bovine thrombin exposed surgical patients was extracted and reviewed. In 38 studies, about half were case reports and 31.5% were interventional trials. In case reports, 41% of authors reported severe coagulopathic adverse events. In contrast, whereas blood complications were common in large trials, no association of harm was established for bovine thrombin product exposure and/or immunization. In this review, later clinical trials failed to reproduce the common and severe coagulopathy predicted by earlier observational studies in bovine exposed patients. This example illustrates that perceptions of safety can change as a function of study design, even for a widely adopted, well established biologic such as thrombin. Caution must be exercised in interpreting evidence from observational studies alone.

Negative emotionality and disconstraint influence PTSD symptom course via exposure to new major adverse life events.

PubMed

Sadeh, Naomi; Miller, Mark W; Wolf, Erika J; Harkness, Kate L

2015-04-01

Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23-68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality over time. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events. Published by Elsevier Ltd.

Neglect, Sexual Abuse, and Witnessing Intimate Partner Violence During Childhood Predicts Later Life Violent Attitudes Against Children Among Kenyan Women: Evidence of Intergenerational Risk Transmission From Cross-Sectional Data.

PubMed

Goodman, Michael L; Hindman, Andrea; Keiser, Philip H; Gitari, Stanley; Ackerman Porter, Katherine; Raimer, Ben G

2017-01-01

Violence against children, including corporal punishment, remains a global concern. Understanding sources of support for corporal punishment within cultures, and the potential for intergenerational transmission of child maltreatment, is essential for policy-development and community engagement to protect children. In this study, we use data from a cross-section of women in Meru County, Kenya ( n = 1,974) to profile attitudes toward violence against children using the Velicer Attitudes Towards Violence-Child subscale. We find reported histories of sexual abuse, emotional and physical neglect, and witnessing interpersonal violence during childhood predict more violent attitudes toward children in adulthood. The pathway between these forms of child maltreatment and violent attitudes is significantly mediated by family function, perceived stress, and attitudes toward violence against women. Interventions to prevent sexual abuse, intimate partner violence, and promote attachments between parents and children may benefit future generations in this population. Furthermore, secondary prevention of the effects of these childhood adversities may require development of social support, improving family function and challenging violent attitudes against women.

Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

PubMed

Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

2018-06-01

Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Fish early life stage: Developing AOPs to support targeted reduction and replacement

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

EPA Science Inventory

Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

EPA Science Inventory

The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

EPA Science Inventory

High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

Tools for in silico target fishing.

PubMed

Cereto-Massagué, Adrià; Ojeda, María José; Valls, Cristina; Mulero, Miquel; Pujadas, Gerard; Garcia-Vallve, Santiago

2015-01-01

Computational target fishing methods are designed to identify the most probable target of a query molecule. This process may allow the prediction of the bioactivity of a compound, the identification of the mode of action of known drugs, the detection of drug polypharmacology, drug repositioning or the prediction of the adverse effects of a compound. The large amount of information regarding the bioactivity of thousands of small molecules now allows the development of these types of methods. In recent years, we have witnessed the emergence of many methods for in silico target fishing. Most of these methods are based on the similarity principle, i.e., that similar molecules might bind to the same targets and have similar bioactivities. However, the difficult validation of target fishing methods hinders comparisons of the performance of each method. In this review, we describe the different methods developed for target prediction, the bioactivity databases most frequently used by these methods, and the publicly available programs and servers that enable non-specialist users to obtain these types of predictions. It is expected that target prediction will have a large impact on drug development and on the functional food industry. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain

PubMed Central

Birnie, D H; Vickers, L E; Hillis, W S; Norrie, J; Cobbe, S M

2005-01-01

Objective: To assess whether antibodies to human heat shock protein 60 (anti-huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an adverse one year prognosis in patients admitted with acute cardiac chest pain. Design: Prospective observational study. Setting: Teaching hospital. Patients: 588 consecutive emergency admissions of patients with acute chest pain of suspected cardiac origin. Main outcome measures: Anti-huhsp60 and anti-mhsp65 titres were assayed on samples drawn on the morning after admission. The end points after discharge were coronary heart disease death, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain. Results: During follow up after discharge (mean of 304 days, range 1–788 days), 277 patients had at least one of the study outcomes. Patients with increased titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95% confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p  =  0.015). Anti-mhsp65 titres were not predictive. Conclusions: Patients admitted with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse one year prognosis. PMID:16103543

Psychopathology, adversity, and creativity: diversifying experiences in the development of eminent African Americans.

PubMed

Damian, Rodica Ioana; Simonton, Dean Keith

2015-04-01

Symptoms associated with mental illness have been hypothesized to relate to creative achievement because they act as diversifying experiences. However, this theory has only been tested on predominantly majority-culture samples. Do tendencies toward mental illness still predict eminent creativity when they coexist with other diversifying experiences, such as early parental death, minority-status, or poverty? These alternative diversifying experiences can be collectively referred to as examples of developmental adversity. This conjecture was tested on a significant sample of 291 eminent African Americans who, by the nature of their status as long-term minorities, would experience more developmental adversity. Replicating majority-culture patterns, African American artists showed higher mental illness rates than African American scientists. Yet the absolute percentages were significantly lower for the African Americans, regardless of profession. Furthermore, mental illness predicted higher eminence levels only for the African American artists, an effect that diminished when controlling for developmental adversity. Because the latter predicted eminence for both artists and scientists, the "madness-to-genius" link probably represents just 1 of several routes by which diversifying experiences can influence eminence. The same developmental ends can be attained by different means. This inference warrants further research using other eminent creators emerging from minority culture populations. (c) 2015 APA, all rights reserved).

Childhood adversities and socioeconomic position as predictors of leisure-time physical inactivity in early adulthood.

PubMed

Kestilä, Laura; Mäki-Opas, Tomi; Kunst, Anton E; Borodulin, Katja; Rahkonen, Ossi; Prättälä, Ritva

2015-02-01

Limited knowledge exists on how childhood social, health-related and economic circumstances predict adult physical inactivity. Our aim was a) to examine how various childhood adversities and living conditions predict leisure-time physical inactivity in early adulthood and b) to find out whether these associations are mediated through the respondent's own education. Young adults aged 18-29 were used from the Health 2000 Study of the Finnish. The cross-sectional data were based on interviews and questionnaires including retrospective information on childhood circumstances. The analyses were carried out on 68% of the original sample (N = 1894). The outcome measure was leisure-time physical inactivity. Only a few of the 11 childhood adversities were related with physical activity in early adulthood. Having been bullied at school was associated with physical inactivity independently of the other childhood circumstances and the respondent's own education. Low parental education predicted leisure-time physical inactivity in men and the association was mediated by the respondent's own education. Respondents with only primary or vocational education were more likely to be physically inactive during leisure-time compared with those with secondary or higher education. There is some evidence that few specific childhood adversities, especially bullying at school, have long-lasting effects on physical activity levels.

Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children's Psychopathology.

PubMed

Gray, Sarah A O; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

2017-03-01

Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth ( n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors.

Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children’s Psychopathology

PubMed Central

Gray, Sarah A. O.; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

2016-01-01

Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth (n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors. PMID:28479668

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

PubMed Central

Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2016-01-01

OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647

[The outcomes of Adoption in the Case of the "British Chinese Adoption Study"].

PubMed

Rushton, Alan

2015-01-01

Practitioners can over-estimate the incidence of problems in adopted children and adults because they do not see those who make good psychological and social adjustments. Research into adoption outcomes can be hard to interpret without information about differing pre-adoption histories. Examples are given of research into three types of adoption: domestic infant adoption, adoptions from public care of maltreated children and international adoption of ex-orphanage children. Although negative outcomes are indisputably evident for some, recovery from adversity is more common than many would predict. It is important to recognize that subsequent nurturing in consistent and stimulating environments can build a platform for effective adaptations to challenges in the future. However, a proper understanding of the consequences of adoption has been limited by the fact that follow-up studies have rarely extended beyond adolescence and early adulthood. The British Chinese Adoption Study is a 50 year follow-up of orphanage girls internationally adopted into the United Kingdom, and is given as an example of good outcomes despite early years of adversity. Scores on mental health assessments were equivalent to the non-adopted, age-matched comparison group of UK women. Most of the women were rated as "good functioning" and educational achievements were many times higher than the comparison women. Life-long adverse effects are not inevitable following early adversity. Improved circumstances can promote recovery and good adult adjustment. Practice and research implications are discussed.

The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences.

PubMed

de Ferranti, Sarah; Mozaffarian, Dariush

2008-06-01

As the prevalence of adiposity soars in both developed and developing nations, appreciation of the close links between obesity and disease increases. The strong relationships between excess adipose tissue and poor health outcomes, including cardiovascular disease, diabetes, and cancer, mandate elucidation of the complex cellular, hormonal, and molecular pathophysiology whereby adiposity initiates and maintains adverse health effects. In this report we review adipocyte metabolism and function in the context of energy imbalance and postprandial nutrient excess, including adipocyte hypertrophy and hyperplasia, adipocyte dysfunction, and other systemic consequences. We also discuss implications for laboratory evaluation and clinical care, including the role of lifestyle modifications. Chronic energy imbalance produces adipocyte hypertrophy and hyperplasia, endoplasmic reticulum stress, and mitochondrial dysfunction. These processes lead to increased intracellular and systemic release of adipokines, free fatty acids, and inflammatory mediators that cause adipocyte dysfunction and induce adverse effects in the liver, pancreatic beta-cells, and skeletal muscle as well as the heart and vascular beds. Several specialized laboratory tests can quantify these processes and predict clinical risk, but translation to the clinical setting is premature. Current and future pharmacologic interventions may target these pathways; modest changes in diet, physical activity, weight, and smoking are likely to have the greatest impact. Adipocyte endoplasmic reticulum and mitochondrial stress, and associated changes in circulating adipokines, free fatty acids, and inflammatory mediators, are central to adverse health effects of adiposity. Future investigation should focus on these pathways and on reversing the adverse lifestyle behaviors that are the fundamental causes of adiposity.

The Roles of Resilience and Childhood Trauma History: Main and Moderating Effects on Postpartum Maternal Mental Health and Functioning

PubMed Central

Sexton, Minden B.; Hamilton, Lindsay; McGinnis, Ellen W.; Rosenblum, Katherine L.; Muzik, Maria

2015-01-01

Objective Recently postpartum women participated to investigate main and moderating influences of resilience and childhood history of maltreatment on posttraumatic stress disorder (PTSD), major depressive disorder (MDD), parental sense of mastery, and family functioning. Method At 4-months postpartum, 214 mothers (145 with a history of childhood abuse or neglect) completed interviews assessing mental health symptoms, positive functioning, resilience and trauma history. Multiple and moderated linear regression with the Connor- Davidson Resilience Scale (CD-RISC) and Childhood Trauma Questionnaires (CTQ) were conducted to assess for main and moderating effects. Results Resilience, childhood trauma severity, and their interaction predicted postpartum PTSD and MDD. In mothers without childhood maltreatment, PTSD was absent irrespective of CD-RISC scores. However, for those with the highest quartile of CTQ severity, 8% of those with highest resilience in contrast with 58% of those with lowest CD-RISC scores met PTSD diagnostic criteria. Similar, in those with highest resilience, no mothers met criteria for postpartum MDD, irrespective of childhood trauma, while for those with lowest quartile of resilience, 25% with lowest CTQ severity and 68% of those with highest CTQ severity were depressed. The CD-RISC, but not the CTQ, was predictive of postpartum sense of competence. The CD-RISC and the CTQ were predictive of postpartum family functioning, though no moderating influence of resilience on childhood trauma was found. Conclusions Resilience is associated with reduced psychopathology and improved wellbeing in all mothers. It further serves as a buffer against psychiatric symptoms following childhood trauma. Such findings may assist in identification of those at greatest risk of adverse functioning postpartum, utilization of resilience-enhancing intervention may benefit perinatal wellness, and reduce intergenerational transmission of risk. PMID:25560192

The roles of resilience and childhood trauma history: main and moderating effects on postpartum maternal mental health and functioning.

PubMed

Sexton, Minden B; Hamilton, Lindsay; McGinnis, Ellen W; Rosenblum, Katherine L; Muzik, Maria

2015-03-15

Recently postpartum women participated to investigate main and moderating influences of resilience and childhood history of maltreatment on posttraumatic stress disorder (PTSD), major depressive disorder (MDD), parental sense of mastery, and family functioning. At 4-months postpartum, 214 mothers (145 with a history of childhood abuse or neglect) completed interviews assessing mental health symptoms, positive functioning, resilience and trauma history. Multiple and moderated linear regression with the Connor-Davidson Resilience Scale (CD-RISC) and Childhood Trauma Questionnaires (CTQ) were conducted to assess for main and moderating effects. Resilience, childhood trauma severity, and their interaction predicted postpartum PTSD and MDD. In mothers without childhood maltreatment, PTSD was absent irrespective of CD-RISC scores. However, for those with the highest quartile of CTQ severity, 8% of those with highest resilience in contrast with 58% of those with lowest CD-RISC scores met PTSD diagnostic criteria. Similar, in those with highest resilience, no mothers met criteria for postpartum MDD, irrespective of childhood trauma, while for those with lowest quartile of resilience, 25% with lowest CTQ severity and 68% of those with highest CTQ severity were depressed. The CD-RISC, but not the CTQ, was predictive of postpartum sense of competence. The CD-RISC and the CTQ were predictive of postpartum family functioning, though no moderating influence of resilience on childhood trauma was found. Resilience is associated with reduced psychopathology and improved wellbeing in all mothers. It further serves as a buffer against psychiatric symptoms following childhood trauma. Such findings may assist in identification of those at greatest risk of adverse functioning postpartum, utilization of resilience-enhancing intervention may benefit perinatal wellness, and reduce intergenerational transmission of risk. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional and cognitive impairment, social environment, frailty and adverse health outcomes in older patients with head and neck cancer, a systematic review.

PubMed

van Deudekom, Floor J; Schimberg, Anouk S; Kallenberg, Marije H; Slingerland, Marije; van der Velden, Lily-Ann; Mooijaart, Simon P

2017-01-01

Older head and neck cancer patients are at increased risk for adverse health outcomes, but little is known about which geriatric assessment associates with poor outcome. The aim is to study the association of functional or cognitive impairment, social environment and frailty with adverse health outcomes in patients with head and neck cancer. Four libraries were searched for studies reporting on an association of functional or cognitive impairment, social environment and frailty with adverse outcomes in head and neck cancer patients. Of 4158 identified citations, 31 articles were included. The mean age was ⩾60years in twelve studies (39%). Geriatric conditions were prevalent: between 40 and 50% of the included participants were functional impaired, around 50% had depressive symptoms, and around 40% did not have a partner. Functional impairment was assessed in 18 studies, two studies reported on a cognitive test, eight studies examined mood and social status was depicted by 14 studies. None of the included studies addressed frailty or objectively measured physical capacity such as hand grip strength, gait speed or balance tests. In 64% of the reported associations, a decline in functional or cognitive impairment, mood or social environment was associated with adverse outcomes. Functional and cognitive impairment, depressive symptoms and social isolation are highly prevalent in head and neck cancer patients and associate with high risk of adverse health outcomes. In the future, these measurements may guide decision-making and customize treatments, but more research is needed to further improve and firmly establish clinical usability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

N-Terminal Pro-B-type Natriuretic Peptide Is Useful to Predict Cardiac Complications Following Lung Resection Surgery

PubMed Central

Lee, Chang Young; Bae, Mi Kyung; Lee, Jin Gu; Kim, Kwan-Wook; Park, In Kyu

2011-01-01

Background Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion An elevated preoperative NT-proBNP level is identified as an independent predictor of cardiac complications following lung resection surgery. PMID:22263123

Impact of Net Atrioventricular Compliance on Clinical Outcome in Mitral Stenosis

PubMed Central

Nunes, Maria Carmo P.; Hung, Judy; Barbosa, Marcia M.; Esteves, William A.; Carvalho, Vinicius T.; Lodi-Junqueira, Lucas; Fonseca Neto, Cirilo P.; Tan, Timothy C.; Levine, Robert A.

2014-01-01

Background Net atrioventricular compliance (Cn) has been reported to be an important determinant of pulmonary hypertension in mitral stenosis (MS). We hypothesized that, as Cn reflects hemodynamic consequences of MS, it may be useful in assessing prognosis. To date, limited data with an assumed Cn cutoff have indicated the need for larger prospective studies. This prospective study was designed to determine the impact of Cn on clinical outcome and its contribution to pulmonary pressure in MS. In addition, we aimed to identify a cutoff value of Cn for outcome prediction in this setting. Methods and Results A total of 128 patients with rheumatic MS without other significant valve disease were prospectively enrolled. Comprehensive echocardiography was performed and Doppler-derived Cn estimated using a previously validated equation. The endpoint was either mitral valve intervention or death. Cn was an important predictor of pulmonary pressure, regardless of classic measures of MS severity. During a median follow-up of 22 months, the endpoint was reached in 45 patients (35%). Baseline Cn predicted outcome, adding prognostic information beyond that provided by mitral valve area and functional status. Cn ≤ 4 mL/mmHg best predicted unfavorable outcome in derivation and validation sets. A subgroup analysis including only initially asymptomatic patients with moderate to severe MS without initial indication for intervention (40.6 % of total) demonstrated that baseline Cn predicted subsequent adverse outcome even after adjusting for classic measures of hemodynamic MS severity (hazard ratio [HR] 0.33, 95% confidence interval [CI] 0.14–0.79, p = 0.013). Conclusions Cn contributes to pulmonary hypertension beyond of stenosis severity itself. In a wide spectrum of MS severity, Cn is a powerful predictor of adverse outcome, adding prognostic value to clinical data and mitral valve area. Importantly, baseline Cn predicts a progressive course with subsequent need for intervention in initially asymptomatic patients. Cn assessment therefore has potential value for clinical risk stratification and monitoring in MS patients. PMID:24097419

Adverse childhood experiences predict earlier age of drinking onset: results from a representative US sample of current or former drinkers.

PubMed

Rothman, Emily F; Edwards, Erika M; Heeren, Timothy; Hingson, Ralph W

2008-08-01

Our goal was to determine whether adverse childhood experiences predicted the age at which drinking was initiated and drinking motives in a representative sample of current or former drinkers in the United States. In 2006, a probability sample of 3592 US current or former drinkers aged 18 to 39 were surveyed. Multinomial logistic regression examined whether each of 10 adverse childhood experiences was associated with earlier ages of drinking onset, controlling for demographics, parental alcohol use, parental attitudes toward drinking, and peers' drinking in adolescence. We also examined whether there was a graded relationship between the number of adverse childhood experiences and age of drinking onset and whether adverse childhood experiences were related to self-reported motives for drinking during the first year that respondents drank. Sixty-six percent of respondents reported >or=1 adverse childhood experiences, and 19% reported experiencing >or=4. The most commonly reported adverse childhood experiences were parental separation/divorce (41.3%), living with a household member who was a problem drinker (28.7%), mental illness of a household member (24.8%), and sexual abuse (19.1%). Of the 10 specific adverse childhood experiences assessed, 5 were significantly associated with initiating drinking at or=21 years of age) after adjustment for confounders, including physical abuse, sexual abuse, having a mentally ill household member, substance abuse in the home, and parental discord or divorce. Compared with those without adverse childhood experiences, respondents with adverse childhood experiences were substantially more likely to report that they drank to cope during the first year that they used alcohol. Results suggest that children with particular adverse childhood experiences may initiate drinking earlier than their peers and that they may be more likely to drink to cope with problems (rather than for pleasure or to be social).

Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials

PubMed Central

Denton, Brian T.; Hayward, Rodney A.

2017-01-01

Background Intensive blood pressure (BP) treatment can avert cardiovascular disease (CVD) events but can cause some serious adverse events. We sought to develop and validate risk models for predicting absolute risk difference (increased risk or decreased risk) for CVD events and serious adverse events from intensive BP therapy. A secondary aim was to test if the statistical method of elastic net regularization would improve the estimation of risk models for predicting absolute risk difference, as compared to a traditional backwards variable selection approach. Methods and findings Cox models were derived from SPRINT trial data and validated on ACCORD-BP trial data to estimate risk of CVD events and serious adverse events; the models included terms for intensive BP treatment and heterogeneous response to intensive treatment. The Cox models were then used to estimate the absolute reduction in probability of CVD events (benefit) and absolute increase in probability of serious adverse events (harm) for each individual from intensive treatment. We compared the method of elastic net regularization, which uses repeated internal cross-validation to select variables and estimate coefficients in the presence of collinearity, to a traditional backwards variable selection approach. Data from 9,069 SPRINT participants with complete data on covariates were utilized for model development, and data from 4,498 ACCORD-BP participants with complete data were utilized for model validation. Participants were exposed to intensive (goal systolic pressure < 120 mm Hg) versus standard (<140 mm Hg) treatment. Two composite primary outcome measures were evaluated: (i) CVD events/deaths (myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or CVD death), and (ii) serious adverse events (hypotension, syncope, electrolyte abnormalities, bradycardia, or acute kidney injury/failure). The model for CVD chosen through elastic net regularization included interaction terms suggesting that older age, black race, higher diastolic BP, and higher lipids were associated with greater CVD risk reduction benefits from intensive treatment, while current smoking was associated with fewer benefits. The model for serious adverse events chosen through elastic net regularization suggested that male sex, current smoking, statin use, elevated creatinine, and higher lipids were associated with greater risk of serious adverse events from intensive treatment. SPRINT participants in the highest predicted benefit subgroup had a number needed to treat (NNT) of 24 to prevent 1 CVD event/death over 5 years (absolute risk reduction [ARR] = 0.042, 95% CI: 0.018, 0.066; P = 0.001), those in the middle predicted benefit subgroup had a NNT of 76 (ARR = 0.013, 95% CI: −0.0001, 0.026; P = 0.053), and those in the lowest subgroup had no significant risk reduction (ARR = 0.006, 95% CI: −0.007, 0.018; P = 0.71). Those in the highest predicted harm subgroup had a number needed to harm (NNH) of 27 to induce 1 serious adverse event (absolute risk increase [ARI] = 0.038, 95% CI: 0.014, 0.061; P = 0.002), those in the middle predicted harm subgroup had a NNH of 41 (ARI = 0.025, 95% CI: 0.012, 0.038; P < 0.001), and those in the lowest subgroup had no significant risk increase (ARI = −0.007, 95% CI: −0.043, 0.030; P = 0.72). In ACCORD-BP, participants in the highest subgroup of predicted benefit had significant absolute CVD risk reduction, but the overall ACCORD-BP participant sample was skewed towards participants with less predicted benefit and more predicted risk than in SPRINT. The models chosen through traditional backwards selection had similar ability to identify absolute risk difference for CVD as the elastic net models, but poorer ability to correctly identify absolute risk difference for serious adverse events. A key limitation of the analysis is the limited sample size of the ACCORD-BP trial, which expanded confidence intervals for ARI among persons with type 2 diabetes. Additionally, it is not possible to mechanistically explain the physiological relationships explaining the heterogeneous treatment effects captured by the models, since the study was an observational secondary data analysis. Conclusions We found that predictive models could help identify subgroups of participants in both SPRINT and ACCORD-BP who had lower versus higher ARRs in CVD events/deaths with intensive BP treatment, and participants who had lower versus higher ARIs in serious adverse events. PMID:29040268

Differences by Veteran/civilian status and gender in associations between childhood adversity and alcohol and drug use disorders.

PubMed

Evans, Elizabeth A; Upchurch, Dawn M; Simpson, Tracy; Hamilton, Alison B; Hoggatt, Katherine J

2018-04-01

To examine differences by US military Veteran status and gender in associations between childhood adversity and DSM-5 lifetime alcohol and drug use disorders (AUD/DUD). We analyzed nationally representative data from 3119 Veterans (n = 379 women; n = 2740 men) and 33,182 civilians (n = 20,066 women; n = 13,116 men) as provided by the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). We used weighted multinomial logistic regression, tested interaction terms, and calculated predicted probabilities by Veteran status and gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pairwise comparisons. Among civilians, women had lower AUD and DUD prevalence than men; however, with more childhood adversity, this gender gap narrowed for AUD and widened for DUD. Among Veterans, in contrast, similar proportions of women and men had AUD and DUD; with more childhood adversity, AUD-predicted probability among men surpassed that of women. Childhood adversity elevated AUD probability among civilian women to levels exhibited by Veteran women. Among men, Veterans with more childhood adversity were more likely than civilians to have AUD, and less likely to have DUD. Childhood adversity alters the gender gap in AUD and DUD risk, and in ways that are different for Veterans compared with civilians. Department of Defense, Veterans Affairs, and community health centers can prevent and ameliorate the harmful effects of childhood adversity by adapting existing behavioral health efforts to be trauma informed, Veteran sensitive, and gender tailored.

Pathways Linking Adverse Childhood Experiences to Cigarette Smoking Among Young Black Men: a Prospective Analysis of the Role of Sleep Problems and Delayed Reward Discounting.

PubMed

Oshri, Assaf; Kogan, Steven; Liu, Sihong; Sweet, Lawrence; Mackillop, James

2017-12-01

African American men experience increases in smoking during the young adult transition. Exposure to childhood adversity, a risk factor which disproportionately affects African American men, has been identified as a robust precursor to health risk behavior in general and cigarette smoking in particular. The intermediate mechanisms that transmit the influence of early adversity to smoking behavior are not well understood. We tested a model of the escalation of smoking behaviors among young adult African American men, investigating sleep disturbance and delayed reward discounting as intermediate factors linking adverse childhood experiences with smoking. Hypotheses were tested with three waves of data (M age-T1  = 20.34, M age-T2  = 21.92, M age-T3  = 23.02) from 505 African American men living in rural counties in South Georgia. Men provided self-report data on their adverse childhood experiences, sleep problems, and smoking behavior using audio-assisted computer self-interviews. Men also completed a computer-based delayed reward discounting task. Structural equation modeling analyses supported our hypotheses: Adverse childhood experiences predicted poor sleep adequacy, which forecast increases in delayed reward discounting; discounting, in turn, predicted increased smoking. Significant indirect pathways were detected linking adversity to discounting via sleep adequacy and linking sleep adequacy to smoking via discounting. Prevention and intervention researchers can draw on these findings to develop programs that focus on sleep adequacy to reduce smoking in African American men exposed to childhood adversity.

The Influence of Childhood Adversity on Rural Black Men's Sexual Risk Behavior.

PubMed

Kogan, Steven M; Cho, Junhan; Oshri, Assaf

2016-12-01

Young Black men living in resource-poor rural environments are disproportionately affected by both adverse childhood experiences and HIV/STIs. The influence of childhood adversity on sexual risk behavior remains to be examined among this vulnerable population. In this study, we investigated the influence of overall adversity as well as three subcomponents, abusive parenting, parental neglect, and witnessing family violence, on men's engagement in sexual risk behavior. We hypothesized that adverse experiences would predict engagement in sexual risk behaviors including multiple sexual partnerships, inconsistent condom use, frequent sexual activity, and concurrent substance abuse and sexual activity. We tested formally the extent to which defensive relational schemas mediated these associations. Hypotheses were tested with data from 505 rural Black men (M age = 20.29, SD = 1.10) participating in the African American Men's Health Project. Participants were recruited using respondent-driven sampling. Self-report data were gathered from participants via audio computer-assisted self-interviews. Bi-factor analyses revealed that, in addition to a common adversity factor, neglect independently predicted sexual risk behavior. Men's defensive relational schemas partially mediated the influence of the common adversity factor as well as the neglect subcomponent on sexual risk behavior. The present research identified a potential risk factor for sexual risk behavior in an understudied and vulnerable population. Adverse childhood experiences in general, and neglect in particular, may place many young Black men at risk for engaging in sexual risk behavior due in part to the influence of these experiences on men's development of relational schemas characterized by defensiveness and mistrust.

Does MAOA Increase Susceptibility to Prenatal Stress in Young Children?

PubMed Central

Massey, Suena H.; Hatcher, Amalia E.; Clark, Caron A.C.; Burns, James L.; Pine, Daniel S.; Skol, Andrew D.; Mroczek, Daniel K.; Espy, Kimberly A.; Goldman, David; Cook, Edwin; Wakschlag, Lauren S.

2017-01-01

Background We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. Methods Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. Results Concurrent stress exposure predicted DB in children (β=.310, p=.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOAxPSExsex on DB (β=.813, p=.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β=.774, p=.015), and as a function of PTE, controlling for PSE (β=.362, p=.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β=−.133, p=.561) nor PTE (β= −.144; p=.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters’ concurrent stress exposure (r=−.240, p=.013). Discussion Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression. PMID:28163169

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Does MAOA increase susceptibility to prenatal stress in young children?

PubMed

Massey, Suena H; Hatcher, Amalia E; Clark, Caron A C; Burns, James L; Pine, Daniel S; Skol, Andrew D; Mroczek, Daniel K; Espy, Kimberly A; Goldman, David; Cook, Edwin; Wakschlag, Lauren S

2017-05-01

We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. Concurrent stress exposure predicted DB in children (β=0.310, p=0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA×PSE×sex on DB (β=0.813, p=0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β=0.774, p=0.015), and as a function of PTE, controlling for PSE (β=0.362, p=0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β=-0.133, p=0.561) nor PTE (β=-0.144; p=0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r=-0.240, p=0.013). Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression.

PubMed

Pagliaccio, David; Pine, Daniel S; Barch, Deanna M; Luby, Joan L; Leibenluft, Ellen

2018-05-01

Cross-sectional, longitudinal, and genetic associations exist between irritability and depression. Prior studies have examined developmental trajectories of irritability, clinical outcomes, and associations with child and familial depression. However, studies have not integrated neurobiological measures. The present study examined developmental trajectories of irritability, clinical outcomes, and cortical structure among preschoolers oversampled for depressive symptoms. Beginning at 3 to 5 years old, a sample of 271 children enriched for early depressive symptoms were assessed longitudinally by clinical interview. Latent class mixture models identified trajectories of irritability severity. Risk factors, clinical outcomes, and cortical thickness were compared across trajectory classes. Cortical thickness measures were extracted from 3 waves of magnetic resonance imaging at 7 to 12 years of age. Three trajectory classes were identified among these youth: 53.50% of children exhibited elevated irritability during preschool that decreased longitudinally, 30.26% exhibited consistently low irritability, and 16.24% exhibited consistently elevated irritability. Compared with other classes, the elevated irritability class exhibited higher rates of maternal depression, early life adversity, later psychiatric diagnoses, and functional impairment. Further, elevated baseline irritability predicted later depression beyond adversity and personal and maternal depression history. The elevated irritability class exhibited a thicker cortex in the left superior frontal and temporal gyri and the right inferior parietal lobule. Irritability manifested with specific developmental trajectories in this sample enriched for early depression. Persistently elevated irritability predicted poor psychiatric outcomes, higher risk for later depression, and decreased overall function later in development. Greater frontal, temporal, and parietal cortical thickness also was found, providing neural correlates of this risk trajectory. Copyright © 2018 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Condliffe, Robin; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

2012-10-01

The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions.

PubMed

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions.

Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

PubMed

Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

2016-11-01

Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization and prediction of adverse events from intensive chronic heart failure management and effect on quality of life: results from the pro-B-type natriuretic peptide outpatient-tailored chronic heart failure therapy (PROTECT) study.

PubMed

Gandhi, Parul U; Szymonifka, Jackie; Motiwala, Shweta R; Belcher, Arianna M; Januzzi, James L; Gaggin, Hanna K

2015-01-01

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01). NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Parental Problem Drinking and Adolescent Externalizing Behaviors: The Mediating Role of Family Functioning

PubMed Central

Schulz, Jessica; Gordon, Mellissa S.; Ohannessian, Christine McCauley

2015-01-01

This study explored relationships among parental problem drinking, family functioning, and adolescent externalizing behaviors. The unique effects of maternal and paternal drinking were examined separately for girls and boys. The sample included 14-19 year old U.S. adolescents (Mage=16.15; SD=.75; 52.5% female) and their parents. Participants completed surveys in the spring of 2007 and 2008. Structural equation modelling was used to conduct path analysis models. Results showed the distinctive and adverse effects of parental problem drinking on adolescent alcohol use, drug use, rule breaking, and aggressive behavior over time. Findings also highlighted the indirect and mediating roles of family functioning. For both girls and boys, family cohesion mediated the relationship between parental problem drinking and adolescent externalizing behaviors. For girls, adolescent-father communication predicted increased externalizing behaviors over time. These findings draw attention to the importance of exploring adolescent and parent gender when examining parental problem drinking, family functioning, and externalizing behaviors. PMID:26073673

Lung function in retired coke oven plant workers.

PubMed Central

Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

1992-01-01

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

Empirical testing AOP network-based hazard prediction combined effect of aromatase inhibition & androgen receptor agonism

EPA Science Inventory

Adverse outcome pathways (AOPs) describe linkages between a specific molecular perturbation resulting from interaction of a chemical with a biomolecule in an organism and one possible adverse outcome of regulatory significance. While individual AOPs have utility, it is recognized...

Use of the adverse outcome pathway framework to represent cross-species consequences of specific pathway perturbations

EPA Science Inventory

The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...

Practitioner Review: Diagnosing childhood resilience--a systemic approach to the diagnosis of adaptation in adverse social and physical ecologies.

PubMed

Ungar, Michael

2015-01-01

With growing interest in resilience among mental health care providers globally, there is a need for a simple way to consider the complex interactions that predict adaptive coping when there is exposure to high levels of adversity such as family violence, mental illness of a child or caregiver, natural disasters, social marginalization, or political conflict. This article presents diagnostic criteria for assessing childhood resilience in a way that is sensitive to the systemic factors that influence a child's wellbeing. The most important characteristics of children who cope well under adversity and avoid problems like depression, PTSD, and delinquency are highlighted. A multidimensional assessment of resilience is presented that examines, first, the severity, chronicity, ecological level, children's attributions of causality, and cultural and contextual relevance of experiences of adversity. Second, promotive and protective factors related to resilience are assessed with sensitivity to the differential impact these have on outcomes depending on a child's level of exposure to adversity. These factors include individual qualities like temperament, personality, and cognitions, as well as contextual dimensions of positive functioning related to the available and accessibility of resources, their strategic use, positive reinforcement by a child's significant others, and the adaptive capacity of the environment itself. Third, an assessment of resilience includes temporal and cultural factors that increase or decrease the influence of protective factors. A decision tree for the diagnosis of resilience is presented, followed by a case study and diagnosis of a 15-year-old boy who required treatment for a number of mental health challenges. The diagnostic criteria for assessing resilience and its application to clinical practice demonstrate the potential usefulness of a systemic approach to understanding resilience among child populations. © 2014 Association for Child and Adolescent Mental Health.

The joint contribution of maternal history of early adversity and adulthood depression to socioeconomic status and potential relevance for offspring development.

PubMed

Bouvette-Turcot, Andrée-Anne; Unternaehrer, Eva; Gaudreau, Hélène; Lydon, John E; Steiner, Meir; Meaney, Michael J

2017-01-01

We examined the interactive effects of maternal childhood adversity and later adulthood depression on subsequent socioeconomic status (SES). Our community sample ranged from 230 to 243 mothers (across measures) drawn from a prospective, longitudinal cohort study. Maternal childhood adversity scores were derived using an integrated measure derived from the Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Index (PBI). Maternal depression was measured in the prenatal period with the Center for Epidemiologic Studies Depression Scale (CES-D). SES measures included maternal highest level of education and family income as obtained prenatally. The analyses yielded significant interaction effects between maternal childhood adversity and prenatal depression that predicted income, prenatally. Women who reported higher levels of childhood adversity combined with higher levels of self-reported depressive symptoms were significantly more likely to live in low SES environments. Results also showed that level of education was predicted by childhood adversity independent of maternal symptoms of depression. The results suggest that SES is influenced by a life course pathway that begins in childhood and includes adversity-related mental health outcomes. Since child health and development is influenced by both maternal mental health and SES, this pathway may also contribute to the intergenerational transmission of the risk for psychopathology in the offspring. The results also emphasize the importance of studying potential precursors of low SES, a well-documented environmental risk factor for poor developmental outcomes in the offspring. Copyright © 2016. Published by Elsevier B.V.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

PubMed Central

Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation.

PubMed

Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim

2016-10-01

Significant disruption in caregiving is associated with increased internalizing symptoms, most notably heightened separation anxiety symptoms during childhood. It is also associated with altered functional development of the amygdala, a neurobiological correlate of anxious behavior. However, much less is known about how functional alterations of amygdala predict individual differences in anxiety. Here, we probed amygdala function following institutional caregiving using very subtle social-affective stimuli (trustworthy and untrustworthy faces), which typically result in large differences in amygdala signal, and change in separation anxiety behaviors over a 2-year period. We hypothesized that the degree of differentiation of amygdala signal to trustworthy versus untrustworthy face stimuli would predict separation anxiety symptoms. Seventy-four youths mean (SD) age = 9.7 years (2.64) with and without previous institutional care, who were all living in families at the time of testing, participated in an fMRI task designed to examine differential amygdala response to trustworthy versus untrustworthy faces. Parents reported on their children's separation anxiety symptoms at the time of scan and again 2 years later. Previous institutional care was associated with diminished amygdala signal differences and behavioral differences to the contrast of untrustworthy and trustworthy faces. Diminished differentiation of these stimuli types predicted more severe separation anxiety symptoms 2 years later. Older age at adoption was associated with diminished differentiation of amygdala responses. A history of institutional care is associated with reduced differential amygdala responses to social-affective cues of trustworthiness that are typically exhibited by comparison samples. Individual differences in the degree of amygdala differential responding to these cues predict the severity of separation anxiety symptoms over a 2-year period. These findings provide a biological mechanism to explain the associations between early caregiving adversity and individual differences in internalizing symptomology during development, thereby contributing to individualized predictions of future clinical outcomes. © 2016 Association for Child and Adolescent Mental Health.

The risk of male adult alcohol dependence: The role of the adverse childhood experiences and ecological executive function.

PubMed

Liu, Zengxun; Yang, Ying; Shi, Zhenchun; Liu, Jintong; Wang, Yang

2016-07-01

To explore the association between male adult alcohol dependence and their adverse childhood experiences as well as ecological executive function. The questionnaires of Adverse Childhood Experiences (ACEs) and Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) were adopted for the assessments of 102 alcohol dependent patients who were diagnosed according to the criteria defined by the International Classification of diseases and related health problems (ICD-10) and 106 healthy volunteers, and the differences between patients and healthy volunteers were analyzed. The percentage of adverse childhood experiences in alcohol dependent patients was significantly higher than that in healthy volunteers (χ(2)=17.28, P<0.01); and the incidences of emotional abuse, physical neglect, violence witness, and substance abuse were significantly higher in alcohol dependent patients than those in healthy volunteers (χ(2)=4.59, 4.46, 10.51, and 44.09 respectively; P<0.05). The ecological executive function analysis showed that the BRIEF total score and scores for each item were all significantly higher in alcohol dependent patients than those of healthy volunteers (P<0.01). The adult alcohol dependence was associated with their adverse childhood experiences and ecological executive function. Then physical neglect and substance abuse of parents in childhood, and emotional control defect in the ecological executive function showed strong association with adult alcohol dependence. Copyright © 2016 Elsevier Inc. All rights reserved.

Robust enzyme design: bioinformatic tools for improved protein stability.

PubMed

Suplatov, Dmitry; Voevodin, Vladimir; Švedas, Vytas

2015-03-01

The ability of proteins and enzymes to maintain a functionally active conformation under adverse environmental conditions is an important feature of biocatalysts, vaccines, and biopharmaceutical proteins. From an evolutionary perspective, robust stability of proteins improves their biological fitness and allows for further optimization. Viewed from an industrial perspective, enzyme stability is crucial for the practical application of enzymes under the required reaction conditions. In this review, we analyze bioinformatic-driven strategies that are used to predict structural changes that can be applied to wild type proteins in order to produce more stable variants. The most commonly employed techniques can be classified into stochastic approaches, empirical or systematic rational design strategies, and design of chimeric proteins. We conclude that bioinformatic analysis can be efficiently used to study large protein superfamilies systematically as well as to predict particular structural changes which increase enzyme stability. Evolution has created a diversity of protein properties that are encoded in genomic sequences and structural data. Bioinformatics has the power to uncover this evolutionary code and provide a reproducible selection of hotspots - key residues to be mutated in order to produce more stable and functionally diverse proteins and enzymes. Further development of systematic bioinformatic procedures is needed to organize and analyze sequences and structures of proteins within large superfamilies and to link them to function, as well as to provide knowledge-based predictions for experimental evaluation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adverse systemic arterial function in patients with selenium deficiency.

PubMed

Chan, Y-H; Siu, C-W; Yiu, K-H; Chan, H-T; Li, S-W; Tam, S; Cheung, B M; Lau, C-P; Lam, T H; Tse, H-F

2012-01-01

Experimental studies have shown that selenium is involved in the synthesis of selenoproteins which might contribute to cardiovascular protection. However, the relationship between selenium deficiency and vascular function in clinical context remains unknown. To investigate for any relationship between selenium deficiency and systemic arterial function in patients with high risk of vascular events. Cross-sectional study. 306 consecutive patients with high risk for cardiovascular events (coronary artery disease 35%, acute/ recurrent ischemic stroke 40%, diabetes mellitus 54%) followed up at internal medicine outpatient clinics. Non-invasive brachial-ankle pulse wave velocity (PWV) was determined using vascular profiling system (VP-2000). Long-term intake of selenium was determined by a validated food frequency questionnaire. Mean daily selenium intake was 59.5 ± 52.1 mcg/day, and mean PWV was 1782.4 ± 418.4 cm/s. Patients with selenium intake <10th percentile had significantly higher PWV as compared to patients with intake ≥ 10th percentile (1968.2 ± 648.9 cm/s versus 1762.2 ± 381.6 cm/s, P=0.010). After adjusting for potential confounders including age, gender, history of hypertension, hyperlipidemia, diabetes and cardiovascular disease, smoking status, use of cardiovascular medications, waist-hip ratio, education/ financial status, physical activity, calorie intake and intake of antioxidant vitamins, deficient selenium intake <10th percentile remained independently predictive of increased PWV by +363.4 cm/s [95% CI: 68.1 to 658.6, P=0.016, relative increase 21%]. Selenium deficiency is associated with adverse arterial function in patients with high risk for vascular events.

Predictors and Clinical Impact of Functional Mitral Stenosis Induced by Restrictive Annuloplasty for Ischemic and Functional Mitral Regurgitation.

PubMed

Kainuma, Satoshi; Taniguchi, Kazuhiro; Toda, Koichi; Funatsu, Toshihiro; Kondoh, Haruhiko; Miyagawa, Shigeru; Yoshikawa, Yasushi; Hata, Hiroki; Saito, Shunsuke; Ueno, Takayoshi; Kuratani, Toru; Daimon, Takashi; Masai, Takafumi; Sawa, Yoshiki

2017-11-24

There are few reports of the determinants of "functional" mitral stenosis in terms of a residual mitral valve (MV) pressure gradient >5 mmHg following restrictive mitral annuloplasty (RMA) or the effect on long-term outcome in patients with functional mitral regurgitation (MR).Methods and Results:Serial cardiac catheterization and echocardiographic studies were performed in 55 patients with functional MR who underwent RMA using a 24/26-mm semi-rigid complete ring. The mean postoperative (1 month) catheter-measured MV gradient was 3.4±1.6 mmHg, which was independently associated with corresponding cardiac output [standardized partial regression coefficient (SPRC)=0.59] and indexed effective orifice area (SPRC=-0.25). Body surface area (BSA) had the greatest contribution to MV gradient (SPRC=0.38), followed by use of a 24-mm ring (SPRC=0.33) and hemodialysis (SPRC=0.26). Receiver-operating characteristic curve analysis demonstrated an optimal BSA cutoff value of 1.86 m 2 to predict post-MV stenosis (21% for <1.86 m 2 vs. 86% for ≥1.86 m 2 , P=0.002). During follow-up (75±32 months), freedom from adverse events did not differ between patients with (n=16) and without (n=39) an MV gradient ≥5 mmHg (log-rank P=0.24). Post-RMA MV gradient was determined not only by the degree of annular reduction but also by patients' hemodynamic factors (e.g., cardiac output). Implantation of a 24/26-mm annuloplasty ring for patients with BSA ≥1.86 m 2 indicated a high likelihood of post-MV stenosis. However, mild MV stenosis did not adversely affect late outcome after RMA.

Hazards of Hospitalization: Residence Prior to Admission Predicts Outcomes

ERIC Educational Resources Information Center

Friedman, Susan M.; Mendelson, Daniel A.; Bingham, Karilee W.; McCann, Robert M.

2008-01-01

Purpose: Previous studies investigating adverse outcomes of hospitalized elders have focused on community-dwelling patients. Given the rapid growth of populations living in other settings, such as assisted living facilities, it is important to understand whether these patients are at higher risk of experiencing specific adverse outcomes during…

Initial investigation of a hypothesized link between thyroid peroxidase inhibition and fish early-life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Early Adversity, Elevated Stress Physiology, Accelerated Sexual Maturation, and Poor Health in Females

ERIC Educational Resources Information Center

Belsky, Jay; Ruttle, Paula L.; Boyce, W. Thomas; Armstrong, Jeffrey M.; Essex, Marilyn J.

2015-01-01

Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for…

Predicting effects of climate and land use change on human well-being via changes in ecosystem services

EPA Science Inventory

Landuse and climate change have affected biological systems in many parts of the world, and are projected to further adversely affect associated ecosystem goods and services, including provisioning of clean air, clean water, food, and biodiversity. Such adverse effects on ecosyst...

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

EPA Science Inventory

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

Psychological distress as a mediator of the association between disease severity and occupational functioning among employed spouses of women recently diagnosed with breast cancer.

PubMed

Manne, Sharon L; Siegel, Scott; Heckman, Carolyn J; Kashy, Deborah A

2015-11-01

The purpose was to evaluate whether patient and spouse cancer-specific distress mediated the association between cancer severity and occupational functioning among employed spouses of women diagnosed with breast cancer. We examined whether sociodemographic characteristics, lower spouse-reported marital quality, and lower spouse self-rated health were associated with poorer spouse occupational functioning. One hundred forty-three currently employed spouses of women diagnosed with breast cancer were administered measures of socioeconomic status, occupational functioning (work absenteeism, low productivity, and poor performance), cancer-specific distress, marital quality, and self-rated health. Patients completed measures of cancer-related distress and functional impairment and cancer stage were collected from medical charts. In the model evaluating work absenteeism, greater patient functional impairment was associated with more absenteeism, but there was no evidence of a mediating effect for either partners' cancer-specific distress. Higher cancer stage and more functional impairment were associated with higher spouse cancer-specific distress, which in turn predicted poorer work productivity. Patient cancer-specific distress did not mediate the association between patient functional impairment or cancer stage and spouse work productivity. Finally, higher cancer stage was associated with more spouse cancer-specific distress, which in turn predicted poorer work performance. There were no direct or indirect effects of the patient's functional impairment on spouse work performance. Distressed spouses are more likely to have poorer work productivity after their partners' breast cancer diagnosis. These spouses may need assistance in managing their distress and the patient's functional impairment to ensure that their work productivity is not adversely affected. Copyright © 2015 John Wiley & Sons, Ltd.

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

PubMed

Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

2016-09-01

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

PubMed

Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

2015-12-01

Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease

PubMed Central

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-01-01

Background The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Methods Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Results Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. Conclusion In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation. PMID:19814829

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease.

PubMed

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-10-08

The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation.

Development of Cardiovascular and Neurodevelopmental Metrics as Sublethal Endpoints for the Fish Embryo Toxicity Test.

PubMed

Krzykwa, Julie C; Olivas, Alexis; Jeffries, Marlo K Sellin

2018-06-19

The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods, as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet weight, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, eye size and cardiovascular related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological and cardiovascular endpoints measured, length, eye size and pericardial area were found to more responsive than the other endpoints, respectively. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole effluent toxicity testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation.

PubMed

Basic-Jukic, Nikolina; Gulin, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Katalinic, Lea; Coric, Marijana; Veda, Marija Varnai; Ivkovic, Vanja; Kes, Petar; Jelakovic, Bojan

2016-01-01

Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF. © 2016 The Author(s) Published by S. Karger AG, Basel.

Adverse childhood event experiences, fertility difficulties and menstrual cycle characteristics.

PubMed

Jacobs, Marni B; Boynton-Jarrett, Renee D; Harville, Emily W

2015-01-01

Increased childhood adversity may be affect adult fertility, however, the mechanism through which this occurs is unclear. Menstrual cycle abnormalities are predictive of fertility difficulties, and stress influences menstrual cycle characteristics. Here, we assess whether adverse childhood experiences (ACEs) are associated with fertility difficulties and menstrual cycle dysregulation, offering a plausible mechanism for the link between lifetime stress and fertility. From April 2012 to February 2014, 742 pregnant and non-pregnant women aged 18-45 years residing in southeastern Louisiana provided information on childhood adversity and reproductive history. Associations between ACEs and fertility difficulties and menstrual cycle patterns were evaluated. As the number of ACEs increased, risk of fertility difficulties and amenorrhea increased (RR = 1.09, 95% CI 1.05-1.13 and RR = 1.07, 95% CI 1.04-1.10, respectively), while fecundability decreased [fecundability ratio (FR) = 0.97, 95% CI 0.95-1.00]. Compared to women with no adversity, women in the high adversity group were more likely to experience both infertility and amenorrhea (RR = 2.75, 95% CI 1.45-5.21 and RR = 2.54, 95% CI 1.52-4.25, respectively), and reduced fecundability (FR = 0.75, 95% CI 0.56-1.00). Although similar patterns were seen for menstrual cycle irregularity, associations were diminished. Associations did not materially change following adjustment for age, body mass index, race, education, smoking and income. Results are constrained by the self-report nature of the study and the limited generalizability of the study population. To our knowledge, this is the first study to present evidence of a link between childhood stressors, menstrual cycle disruption and fertility difficulties. The effect of childhood stress on fertility may be mediated through altered functioning of the HPA axis, acting to suppress fertility in response to less than optimal reproductive circumstances.

Systemic effects of intranasal steroids: an endocrinologist's perspective.

PubMed

Allen, D B

2000-10-01

Intranasal steroids (INSs) are established as first-line treatment for allergic rhinitis. Extensive use of INSs with few reported adverse events supports the safety of these medications. Nevertheless, the prescription of more potent INSs for consistent and more prolonged use to younger and older patients, often in combination with inhaled corticosteroids, justifies the careful examination of their potential adverse systemic effects. Systemic bioavailability of INSs, by way of nasal and intestinal absorption, can be substantial; but current INSs vary significantly in their degree of first-pass hepatic inactivation and clearance from the body of the swallowed drug. For safety studies of INSs, distinguishing detectable physiologic perturbations from important adverse events is aided by an understanding of normal endocrine physiology and the methods used to test these systems. A review of available information indicates that (1) sensitive tests can measure the effects of INSs on biologic feedback systems, but they do not accurately predict clinically relevant adverse effects; (2) the primary factors that influence the relationship between therapeutic and adverse systemic effects of INSs are dosing frequency and efficiency of hepatic inactivation of swallowed drug; (3) INS treatment in recommended doses does not cause clinically significant hypothalamic-pituitary-adrenal axis suppression; (4) growth suppression can occur with twice-daily administration of certain INSs but does not appear to occur with once-daily dosing or with agents with more complete first-pass hepatic inactivation; (5) harmful effects of INSs on bone metabolism have not yet been adequately studied but would not be expected with the use of an INS dose and dosing frequency that do not suppress basal hypothalamic-pituitary-adrenal axis function or growth; and (6) these conclusions apply to INS treatment alone and in recommended doses-the risk of adverse effects in individual patients who are treated with INSs is increased by excessive dosing or concomitant inhaled corticosteroid or other topical corticosteroid therapy.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions

PubMed Central

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions. PMID:29755394

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

PubMed Central

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

PubMed

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Revolutionizing Toxicity Testing For Predicting Developmental Outcomes (DNT4)

EPA Science Inventory

Characterizing risk from environmental chemical exposure currently requires extensive animal testing; however, alternative approaches are being researched to increase throughput of chemicals screened, decrease reliance on animal testing, and improve accuracy in predicting adverse...

Predictive Models and Computational Embryology

EPA Science Inventory

EPA’s ‘virtual embryo’ project is building an integrative systems biology framework for predictive models of developmental toxicity. One schema involves a knowledge-driven adverse outcome pathway (AOP) framework utilizing information from public databases, standardized ontologies...

Poor actigraphic and self-reported sleep patterns predict delinquency and daytime impairment among at-risk adolescents.

PubMed

Stone, Kristen C; Cuellar, Crystal R; Miller-Loncar, Cynthia L; LaGasse, Linda L; Lester, Barry M

2015-09-01

To evaluate associations between actigraphic sleep patterns, subjective sleep quality, and daytime functioning (ie, sleepiness, symptoms of depression, and delinquency and other conduct problems) in at-risk adolescents. Prospective, observational cohort study. Providence, RI, predominantly home and school and 2 visits to the Brown Center for the Study of Children at Risk. A diverse group of low-income 13-year-olds (n = 49) with and without prenatal drug exposure. None. Actigraphy, sleep diaries, and sleep and health questionnaires. Above and beyond the effects of prenatal drug exposure and postnatal adversity, actigraphic daytime sleep was a significant predictor of daytime sleepiness and delinquency. Subjective sleep quality was a significant predictor of daytime sleepiness, delinquency, and depressive symptoms. Later bed times predicted increased delinquency. There was a unique effect of actigraphic daytime sleep duration, subjective nighttime sleep quality, and bedtime on daytime functioning (ie, sleepiness, symptoms of depression, and delinquency and other conduct problems) of at-risk adolescents. In these vulnerable youth, these problematic sleep patterns may contribute to feeling and behaving poorly. Intervention studies with at-risk teens should be conducted to further explore the role of these sleep parameters on daytime functioning. Copyright © 2015 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Mitochondrial dysfunction: a key player in the pathogenesis of cardiovascular diseases linked to air pollution.

PubMed

Boovarahan, Sri Rahavi; Kurian, Gino A

2018-01-18

Air pollution has become an environmental burden with regard to non-communicable diseases, particularly heart disease. It has been reported that air pollution can accelerate the development of heart failure and atrial fibrillation. Air pollutants encompass various particulate matters (PMs), which change the blood composition and heart rate and eventually leads to cardiac failure by triggering atherosclerotic plaque ruptures or by developing irreversible ischemia. A series of major epidemiological and observational studies have established the noxious effect of air pollutants on cardiovascular diseases (CVD), but the underlying molecular mechanisms of its susceptibility and the pathological disease events remain largely elusive and are predicted to be initiated in the cell organelle. The basis of this belief is that mitochondria are one of the major targets of environmental toxicants that can damage mitochondrial morphology, function and its DNA (manifested in non-communicable diseases). In this article, we review the literature related to air pollutants that adversely affect the progression of CVD and that target mitochondrial morphological and functional activities and how mitochondrial DNA (mtDNA) copy number variation, which reflects the airborne oxidant-induced cell damage, correlates with heart failure. We conclude that environmental health assessment should focus on the cellular/circulatory mitochondrial functional copy number status, which can predict the outcome of CVD.

The Costs of Depression

PubMed Central

Kessler, Ronald C.

2011-01-01

Brief summary Data are reviewed on the societal costs of major depressive disorder (MDD). Early-onset MDD is found to predict difficulties in subsequent role transitions, including low educational attainment, high risk of teen child-bearing, marital disruption, and unstable employment. Among people with specific social and productive roles, MDD is found to predict significant decrements in role functioning (e.g., low marital quality, low work performance, low earnings). MDD is also associated with elevated risk of onset, persistence, and severity of a wide range of chronic physical disorders as well as with increased early mortality due to an even wider range of physical disorders and to suicide. Although effectiveness trials show that expanded MDD treatment can reverse many of these adverse effects, only a minority of people with MDD receives treatment and the quality of treatment is unacceptably low among the majority of those in treatment. PMID:22370487

A Relevance Vector Machine-Based Approach with Application to Oil Sand Pump Prognostics

PubMed Central

Hu, Jinfei; Tse, Peter W.

2013-01-01

Oil sand pumps are widely used in the mining industry for the delivery of mixtures of abrasive solids and liquids. Because they operate under highly adverse conditions, these pumps usually experience significant wear. Consequently, equipment owners are quite often forced to invest substantially in system maintenance to avoid unscheduled downtime. In this study, an approach combining relevance vector machines (RVMs) with a sum of two exponential functions was developed to predict the remaining useful life (RUL) of field pump impellers. To handle field vibration data, a novel feature extracting process was proposed to arrive at a feature varying with the development of damage in the pump impellers. A case study involving two field datasets demonstrated the effectiveness of the developed method. Compared with standalone exponential fitting, the proposed RVM-based model was much better able to predict the remaining useful life of pump impellers. PMID:24051527

Practical Methodology for the Inclusion of Nonlinear Slosh Damping in the Stability Analysis of Liquid-Propelled Space Vehicles

NASA Technical Reports Server (NTRS)

Ottander, John A.; Hall, Robert A.; Powers, J. F.

2018-01-01

A method is presented that allows for the prediction of the magnitude of limit cycles due to adverse control-slosh interaction in liquid propelled space vehicles using non-linear slosh damping. Such a method is an alternative to the industry practice of assuming linear damping and relying on: mechanical slosh baffles to achieve desired stability margins; accepting minimal slosh stability margins; or time domain non-linear analysis to accept time periods of poor stability. Sinusoidal input describing functional analysis is used to develop a relationship between the non-linear slosh damping and an equivalent linear damping at a given slosh amplitude. In addition, a more accurate analytical prediction of the danger zone for slosh mass locations in a vehicle under proportional and derivative attitude control is presented. This method is used in the control-slosh stability analysis of the NASA Space Launch System.

A relevance vector machine-based approach with application to oil sand pump prognostics.

PubMed

Hu, Jinfei; Tse, Peter W

2013-09-18

Oil sand pumps are widely used in the mining industry for the delivery of mixtures of abrasive solids and liquids. Because they operate under highly adverse conditions, these pumps usually experience significant wear. Consequently, equipment owners are quite often forced to invest substantially in system maintenance to avoid unscheduled downtime. In this study, an approach combining relevance vector machines (RVMs) with a sum of two exponential functions was developed to predict the remaining useful life (RUL) of field pump impellers. To handle field vibration data, a novel feature extracting process was proposed to arrive at a feature varying with the development of damage in the pump impellers. A case study involving two field datasets demonstrated the effectiveness of the developed method. Compared with standalone exponential fitting, the proposed RVM-based model was much better able to predict the remaining useful life of pump impellers.

Visuoperceptual repetition priming and progression of parkinsonian signs in aging

PubMed Central

Fleischman, Debra A.; Buchman, Aron S.; Bienias, Julia L.; Bennett, David A.

2009-01-01

Parkinsonian signs in older persons are associated with numerous adverse health outcomes, however there is limited information about factors which predict progression of these signs. Using generalized linear models, we examined the association between efficiency in visuoperceptual and conceptual processing, measured by repetition priming, and rate of change in parkinsonian signs in a large sample of older persons without cognitive impairment or Parkinson’s disease. Subjects with better visuoperceptual priming, measured by threshold word-identification and word-stem completion, at study baseline, progressed more slowly during follow-up of up to 11 years. Conceptual priming was not associated with change in parkinsonian signs. The findings demonstrate that individual differences in visuoperceptual efficiency, measured by repetition priming, occur in older persons without cognitive impairment and predict important changes in motor function. Reduced visuoperceptual priming in aging may be an early signal of vulnerability in a corticostrial circuit that contributes to sensorimotor integration. PMID:17709154

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue and represent a significant burden to patients, healthcare providers, and the pharmaceutical industry. • This review details the current state of the art in biomarkers of ADRs (both genetic and circulating). There is still significant variability in patient response which cannot be explained by current knowledge of genetic risk factors for ADRs; however, we discussed how specific advances in genomics have the potential to yield better and more predictive models. • Many current clinically utilized circulating biomarkers of tissue injury are valid biomarkers for a number of ADRs. However, they often give little insight into the specific cell or tissue subtype which may be affected. Emerging circulating biomarkers with potential to provide greater information on the etiology/pathophysiology of ADRs are described.

Obesity and reproductive function: a review of the evidence.

PubMed

Klenov, Violet E; Jungheim, Emily S

2014-12-01

Over the last decade, the evidence linking obesity to impaired reproductive function has grown. In this article, we review this evidence and discuss the underlying pathophysiology. Obese women are less likely than normal-weight women to achieve pregnancy. Female obesity adversely affects reproductive function through alterations in the hypothalamic-pituitary-ovarian axis, oocyte quality, and endometrial receptivity. It is unclear which mechanism contributes the most to subfecundity, and it is likely a cumulative process. Emerging data highlight the contribution of male obesity to impaired reproductive function and that couple obesity has synergistic adverse effects. Once pregnant, obese women are at higher risk for adverse pregnancy outcomes. Weight loss improves reproductive potential in obese patients. As obese women surpass 35 years of age, age may be more important than body mass index in determining reproductive potential. Obstetrician gynecologists need to be aware of the negative impact of obesity on reproductive function so that they appropriately counsel their patients. Further work is needed to clarify the underlying pathophysiology responsible for adverse effects of obesity on reproduction so that novel treatment approaches may be developed.

How can the study of physiological reactivity contribute to our understanding of adversity and resilience processes in development?

PubMed

Obradović, Jelena

2012-05-01

The focus of this article is to present current progress in understanding the interplay among adversity, physiological sensitivity to context, and adaptive functioning, with an emphasis on implications and future directions for resilience researchers. It includes a review of current literature that demonstrates (a) links between various levels of adversity exposure and variability in physiological reactivity, (b) how the interplay between children's physiological reactivity and different sources of risk and adversity relates to variability in adaptive functioning, and (c) various approaches for capturing a more dynamic nature of physiological reactivity and related processes. Throughout, important conceptual and empirical issues are highlighted.

Prediction of adverse drug reactions using decision tree modeling.

PubMed

Hammann, F; Gutmann, H; Vogt, N; Helma, C; Drewe, J

2010-07-01

Drug safety is of great importance to public health. The detrimental effects of drugs not only limit their application but also cause suffering in individual patients and evoke distrust of pharmacotherapy. For the purpose of identifying drugs that could be suspected of causing adverse reactions, we present a structure-activity relationship analysis of adverse drug reactions (ADRs) in the central nervous system (CNS), liver, and kidney, and also of allergic reactions, for a broad variety of drugs (n = 507) from the Swiss drug registry. Using decision tree induction, a machine learning method, we determined the chemical, physical, and structural properties of compounds that predispose them to causing ADRs. The models had high predictive accuracies (78.9-90.2%) for allergic, renal, CNS, and hepatic ADRs. We show the feasibility of predicting complex end-organ effects using simple models that involve no expensive computations and that can be used (i) in the selection of the compound during the drug discovery stage, (ii) to understand how drugs interact with the target organ systems, and (iii) for generating alerts in postmarketing drug surveillance and pharmacovigilance.

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

PubMed

Asselmann, E; Stender, J; Grabe, H J; König, J; Schmidt, C O; Hamm, A O; Pané-Farré, C A

2018-01-01

Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. Data were assessed retrospectively and might be subject to recall biases. Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. Copyright © 2017. Published by Elsevier B.V.

An elevated gap between admission and A1C-derived average glucose levels is associated with adverse outcomes in diabetic patients with pyogenic liver abscess.

PubMed

Liao, Wen-I; Sheu, Wayne Huey-Herng; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Yu-Long; Tsai, Shih-Hung

2013-01-01

To assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA). Clinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004-2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes. Diabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap<72 mg/dL. Multivariate analysis revealed that an elevated glycemic gap≥72 mg/dL was important predictor of adverse outcomes. A glycemic gap≥72 mg/dL, rather than admission hyperglycemia or chronic glycemic control, was significantly correlated with adverse outcomes in diabetic PLA patients. Poorer chronic glycemic control in diabetic PLA patients is associated with high incidence of KP infection, hypoalbuminemia and longer hospital stay.

Does the Size of the Effect of Adverse Events at High Ages on Daily-Life Physical Functioning Depend on the Economic Conditions Around Birth?

PubMed

Scholte, Robert; van den Berg, Gerard J; Lindeboom, Maarten; Deeg, Dorly J H

2017-01-01

This paper considers determinants of physical functional limitations in daily-life activities at high ages. Specifically, we quantify the extent to which the impact of adverse life events on this outcome is larger in case of exposure to adverse economic conditions early in life. Adverse life events include bereavement, severe illness in the family, and the onset of chronic diseases. We use a longitudinal data set of individuals born in the first decades of the 20th century. The business cycle around birth is used as an indicator of economic conditions early in life. We find that the extent to which functional limitations suffer from the onset of chronic diseases is larger if the individual was born in a recession. The long-run effect of economic conditions early in life on functional limitations at high ages runs primarily via this life event. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

Adverse Housing Conditions and Early-Onset Delinquency.

PubMed

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure.

PubMed

Tang, W H Wilson; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

2015-02-01

Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6-12.1) μmol/L, 10.9 (8.4-14.0) μmol/L, and 43.8 (37.1-53.0) μmol/L, respectively, and were correlated with each other (all P < .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9-13.2] vs 4.8 [3.4-9.8] μmol/L; P = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7-14.8] vs 4.7 [3.4-11.3] μmol/L; P = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95% CI 1.22-2.20; P = .001), betaine (HR 1.51, 95% CI 1.10-2.08; P = .01), and TMAO (HR 1.48, 95% CI 1.10-1.96; P = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95% CI 1.03-2.14; P = .03). Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

PubMed

Lapp, Hannah E; Ahmed, Sarah; Moore, Celia L; Hunter, Richard G

2018-02-21

Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing a Theoretical Model of Perceived Self-Efficacy for Cancer-Related Fatigue Self-Management and Optimal Physical Functional Status

PubMed Central

Hoffman, Amy J.; von Eye, Alexander; Gift, Audrey G.; Given, Barbara A.; Given, Charles W.; Rothert, Marilyn

2009-01-01

Background Critical gaps exist in the understanding of cancer symptoms, particularly for cancer-related fatigue (CRF). Existing theories and models do not examine the key role perceived self-efficacy (PSE) plays in a person's ability to manage symptoms. Objectives To test the hypothesis that physical functional status (PFS) is predicted through patient characteristics, CRF, other symptoms, and PSE for fatigue self-management in persons with cancer. Methods This study is a secondary data analysis from the baseline observation of two randomized control trials. The combined data set includes 298 subjects who were undergoing a course of chemotherapy. Key variables included physiological and contextual patient characteristics, the severity from CRF and other symptoms, PSE, and PFS. Path analysis examined the relationships among the variables in the proposed theoretical model. Results Persons with cancer reported CRF as the most prevalent symptom among a mean of 7.4 other concurrent symptoms. The severity from CRF had a direct and indirect effect on PFS, with CRF having a direct adverse impact on PFS (t = -7.02) and an indirect adverse effect as part of the severity from the other symptoms (t = 9.69) which also adversely impacted PFS (t = -2.71). Consistent with the proposed theoretical model, PSE had a positive effect on the PFS (t = 2.87) of persons with cancer while serving as a mediator between CRF severity and PFS. Discussion Cancer-related fatigure is prevalent and related to the presence of other symptoms, and PSE for fatigue self-management is an important factor influencing CRF and PFS. A foundation is provided for future intervention studies to increase PSE to achieve optimal PFS in persons with cancer. PMID:19092553

Predictive Models and Computational Toxicology (II IBAMTOX)

EPA Science Inventory

EPA’s ‘virtual embryo’ project is building an integrative systems biology framework for predictive models of developmental toxicity. One schema involves a knowledge-driven adverse outcome pathway (AOP) framework utilizing information from public databases, standardized ontologies...

Predictive Models of Liver Cancer

EPA Science Inventory

Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

Development and evaluation of adverse outcome pathways predicting adverse effects of conazole fungicides on avian species

EPA Science Inventory

Conazoles are a class of fungicides commonly used in agriculture and as pharmaceuticals to prevent the spread of fungus through inhibition of cytochrome P450 14á-demethylase (CYP51). However these fungicides are known to act promiscuously on other cytochrome P450 enzymes (...

Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

EPA Science Inventory

The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

Stress, Behavior and Health: Developing a Model for Predicting Post-Deployment Morbidity, Mortality and Other Adverse Outcomes

DTIC Science & Technology

1999-07-01

related health outcomes and risk factors for adverse health events. A secondary effort is to link self-reports of stress and subsequent increases in...Gulf War era veterans, information critical to the interpretation of postwar differences between these two groups . We have identified potential

The Impact of Postnatal Depression and Associated Adversity on Early Mother-Infant Interactions and Later Infant Outcome.

ERIC Educational Resources Information Center

Murray, Lynne; And Others

1996-01-01

Examined the impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcomes at 18 months. (MDM)

B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...

Chemical-agnostic hazard prediction: statistical inference of in vitro toxicity pathways from proteomics responses to chemical mixtures

EPA Science Inventory

Toxicity pathways have been defined as normal cellular pathways that, when sufficiently perturbed as a consequence of chemical exposure, lead to an adverse outcome. If an exposure alters one or more normal biological pathways to an extent that leads to an adverse toxicity outcome...

Prenatal Family Adversity and Maternal Mental Health and Vulnerability to Peer Victimisation at School

ERIC Educational Resources Information Center

Lereya, Suzet Tanya; Wolke, Dieter

2013-01-01

Background: Prenatal stress has been shown to predict persistent behavioural abnormalities in offspring. Unknown is whether prenatal stress makes children more vulnerable to peer victimisation. Methods: The current study is based on the Avon Longitudinal Study of Parents and Children, a prospective community-based study. Family adversity, maternal…

Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction

EPA Science Inventory

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of t...

Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction (Poster)

EPA Science Inventory

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of me...

Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study

PubMed Central

Trotta, Antonella; Iyegbe, Conrad; Di Forti, Marta; Sham, Pak C.; Campbell, Desmond D.; Cherny, Stacey S.; Mondelli, Valeria; Aitchison, Katherine J.; Murray, Robin M.

2016-01-01

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis. PMID:27648571

Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

PubMed Central

Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

2016-01-01

We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

Predictive Factors of Nivolumab-induced Hypothyroidism in Patients with Non-small Cell Lung Cancer.

PubMed

Maekura, Toshiya; Naito, Maiko; Tahara, Masahiro; Ikegami, Naoya; Kimura, Yohei; Sonobe, Shoko; Kobayashi, Takehiko; Tsuji, Taisuke; Minomo, Shojiro; Tamiya, Akihiro; Atagi, Shinji

2017-01-01

Although immune checkpoint inhibitors play an important role in the therapy of lung cancer, they are associated with various immune-related adverse events and predictive factors of them are unclear. In this study, we investigated predictive factors of nivolumab-induced hypothyroidism which is one of the adverse events in patients with lung cancer. Patients with non-small-cell lung cancer who were administered nivolumab at our hospital between December 2015 and May 2016 were retrospectively enrolled. The thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid peroxidase (TPO) antibody, and thyroglobulin antibody levels of each patient were analyzed. Of the 64 patients enrolled, 5 (7.8%) developed hypothyroidism after treatment with nivolumab. The TPO and thyroglobulin antibodies were significantly positive in patients who developed primary hypothyroidism. TPO and thyroglobulin antibody levels at baseline may be predictive of hypothyroidism. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control.

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; Wigal, Timothy; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH)-related adverse events are well characterized. Their predictors and their relationship with therapeutic effects are less well understood. Here we examine these issues in relation to two long-acting formulations. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Parents also completed the Barkley Stimulant Side Effect Rating Scale (BSSERS). The BSSERS had six factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and aches. Treatment effects were seen only for emotionality (which improved) and sleep and appetite (which worsened). Adverse events were not predictable from personal and clinical characteristics of patients. Sleep/appetite adverse events were not associated with therapeutic effects. Improvements in attention-deficit/hyperactivity disorder (ADHD) and emotionality were correlated. The results support a narrow conceptualization of MPH adverse events with problems restricted to appetite and sleep. These effects were not predictable on the basis of available information and may be due to an underlying mechanism rather distinct from those determining therapeutic effects.

The sFlt-1/PlGF ratio associates with prolongation and adverse outcome of pregnancy in women with (suspected) preeclampsia: analysis of a high-risk cohort.

PubMed

Saleh, Langeza; Verdonk, Koen; Jan Danser, A H; Steegers, Eric A P; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy

2016-04-01

To evaluate the additive value of the sFlt-1/PlGF ratio for diagnosing preeclampsia (PE) and predicting prolongation of pregnancy and adverse outcome in a cohort of women with PE or at high risk of PE. Patients with suspected or confirmed clinical PE were recruited. At time of inclusion blood for measurement of sFlt-1and PlGF was taken. Values were determined after delivery. A cut-off ratio of ≥85 was defined as a positive test. A total of 107 patients were included. Of the patients, 62 (58%) met the clinical criteria of PE at time of blood sampling. In 10% of these patients (n=6) the ratio was <85 (false negative), whereas in 7% (n=3) of patients without clinical PE the ratio was ≥85 (false positive), resulting in positive and negative predictive values of 95% and 88% respectively. One patient with false positive ratio developed superimposed PE and 2 developed gestational hypertension, and adverse outcome occurred in all three. An adverse pregnancy outcome was only encountered in 1 of the 6 patients with a false negative ratio. Using a binary regression model with adjustment for gestational age <34 weeks, the adverse outcome risk was 11 times increased on the basis of clinical PE, and 30 times on the basis of an elevated ratio (P=0.036). The additive value of an increased ratio for diagnosing PE is limited since most patients with clinical PE also have a positive ratio. However, an elevated ratio is superior to the clinical diagnosis of PE for predicting an adverse pregnancy outcome. Furthermore, irrespective of clinical PE, a low ratio is inversely correlated with prolongation of pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Defining clinical deterioration.

PubMed

Jones, Daryl; Mitchell, Imogen; Hillman, Ken; Story, David

2013-08-01

To review literature reporting adverse events and physiological instability in order to develop frameworks that describe and define clinical deterioration in hospitalised patients. Literature review of publications from 1960 to August 2012. Conception and refinement of models to describe clinical deterioration based on prevailing themes that developed chronologically in adverse event literature. We propose four frameworks or models that define clinical deterioration and discuss the utility of each. Early attempts used retrospective chart review and focussed on the end result of deterioration (adverse events) and iatrogenesis. Subsequent models were also retrospective, but used discrete complications (e.g. sepsis, cardiac arrest) to define deterioration, had a more clinical focus, and identified the concept of antecedent physiological instability. Current models for defining clinical deterioration are based on the presence of abnormalities in vital signs and other clinical observations and attempt to prospectively assist clinicians in predicting subsequent risk. However, use of deranged vital signs in isolation does not consider important patient-, disease-, or system-related factors that are known to adversely affect the outcome of hospitalised patients. These include pre-morbid function, frailty, extent and severity of co-morbidity, nature of presenting illness, delays in responding to deterioration and institution of treatment, and patient response to therapy. There is a need to develop multiple-variable models for deteriorating ward patients similar to those used in intensive care units. Such models may assist clinician education, prospective and real-time patient risk stratification, and guide quality improvement initiatives that prevent and improve response to clinical deterioration. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of safety in clinical use of generic paclitaxel [NK] for injection.

PubMed

Tsukiyama, Ikuto; Hotta, Kazuo; Takeuchi, Masayuki; Onishi, Masahumi; Toyama, Yukio; Saito, Hiroko; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Hasegawa, Takaaki

2012-04-01

The introduction of generic drugs is a favored strategy in reducing medical costs, but some clinicians are often reluctant to use them because of lack of information with regard to their side effects. Generic paclitaxel [NK] differs from the proprietary version, Taxol®, in containing added citric acid and a more pure form of castor oil. However, little information exists regarding the effects of these additives on adverse events such as vascular pain, phlebitis, hypersensitivity and hepatic dysfunction. To compensate for this lack of information and to validate the safety of using generic paclitaxel, we investigated adverse events in response to generic paclitaxel [NK]. Our investigation focused on patients treated with both the proprietary formulation (Taxol® for injection) and the generic version(paclitaxel [NK] for injection)sequentially from April 2008 to March 2009. Adverse events were investigated retrospectively. Incidence of vascular pain, phlebitis and hypersensitivity was similar to that with the original product. Although the expression of some liver enzymes was slightly increased and some gastrointestinal events were reduced following generic paclitaxel [NK] treatment there was no statistically significant difference. The profiles of other adverse events were not significantly different. Increased vascular pain and phlebitis, predicted due to low pH conditions caused by citric acid, were not observed. Similarly, the pure castor oil included in generic paclitaxel [NK] did not influence hypersensitivity and hepatic function. We found no significant differences in our study of proprietary and generic paclitaxel [NK]. Thus, clinicians have no reason for prejudice against using generic paclitaxel [NK] on the basis of increased risk of side effects.

Usefulness of fetal urine production measurement for prediction of perinatal outcomes in uteroplacental insufficiency.

PubMed

Lee, Seung Mi; Jun, Jong Kwan; Kim, Su Ah; Lee, Eun Ja; Kim, Byoung Jae; Park, Chan-Wook; Park, Joong Shin

2014-12-01

To evaluate whether fetal urine production measurement is useful for predicting adverse outcomes in patients with uteroplacental insufficiency. We enrolled patients with uteroplacental insufficiency at 24 to 40 weeks' gestation and normal pregnancies matched for gestational age and divided them into 3 groups according to perinatal outcomes: group 1 (n = 141), a control group of normal pregnancies; group 2 (n = 29), uteroplacental insufficiency without adverse outcomes; and group 3 (n = 18), uteroplacental insufficiency with adverse outcomes. An adverse outcome was defined as 1 or more of the following: (1) cesarean delivery because of fetal distress; (2) admission to the neonatal intensive care unit; (3) cord arterial pH less than 7.15 at birth; and (4) low 5-minute Apgar score (<7). The fetal urine production rate was obtained by serial bladder volume measurement using virtual organ computer-aided analysis. For bladder volume determination, we scanned the bladder in the 3-dimensional mode and defined the bladder surface contour in the reference plane, repeating the rotation of the reference plane with an angle of 30° and determining the surface contour on each plane. Statistical methods, including the Mann-Whitney U test, Fisher exact test, χ(2) test, and Kruskal-Wallis analysis of variance, were used. Group 3 had a lower mean fetal urine production rate than groups 1 and 2, whereas the urine production rate was not different between groups 1 and 2 (group 1, 49.0 mL/h; group 2, 59.4 mL/h; group 3, 20.7 mL/h; P < .001 between groups 1 and 3 and between groups 2 and 3). This difference between groups 2 and 3 remained significant after adjusting for the amniotic fluid index, umbilical artery Doppler pulsatility index, and presence of fetal growth restriction. Uteroplacental insufficiency cases with adverse perinatal outcomes had a lower fetal urine production rate than those without adverse outcomes. This difference might be used to predict adverse perinatal outcomes in uteroplacental insufficiency. © 2013 by the American Institute of Ultrasound in Medicine.

Predicting Adverse Outcomes After Myocardial Infarction Among Patients With Diabetes Mellitus.

PubMed

Arnold, Suzanne V; Spertus, John A; Jones, Philip G; McGuire, Darren K; Lipska, Kasia J; Xu, Yaping; Stolker, Joshua M; Goyal, Abhinav; Kosiborod, Mikhail

2016-07-01

Although patients with diabetes mellitus experience high rates of adverse events after acute myocardial infarction (AMI), including death and recurrent ischemia, some diabetic patients are likely at low risk, whereas others are at high risk. We sought to develop prediction models to stratify risk after AMI in patients with diabetes mellitus. We developed prediction models for long-term mortality and angina among 1613 patients with diabetes mellitus discharged alive after AMI from 24 US hospitals and then validated the models in a separate, multicenter registry of 786 patients with diabetes mellitus. Event rates in the derivation cohort were 27% for 5-year mortality and 27% for 1-year angina. Parsimonious prediction models demonstrated good discrimination (c-indices=0.78 and 0.69, respectively) and excellent calibration. Within the context of the predictors we estimated, the strongest predictors for mortality were higher creatinine, not working at the time of the AMI, older age, lower hemoglobin, left ventricular dysfunction, and chronic heart failure. The strongest predictors for angina were angina burden in the 4 weeks before the AMI, younger age, history of prior coronary bypass graft surgery, and non-white race. The lowest and highest deciles of predicted risk ranged from 4% to 80% for mortality and 12% to 59% for angina. The models also performed well in external validation (c-indices=0.78 and 0.73, respectively). We found a wide range of risk for adverse outcomes after AMI in diabetic patients. Predictive models can identify patients with diabetes mellitus for whom closer follow-up and aggressive secondary prevention strategies should be considered. © 2016 American Heart Association, Inc.

Childhood abuse affects emotional closeness with family in mid- and later life.

PubMed

Savla, J Tina; Roberto, Karen A; Jaramillo-Sierra, Ana L; Gambrel, Laura Eubanks; Karimi, Hassan; Butner, L Michelle

2013-06-01

Knowledge about the effects of early life adversity on kin relationships in later years is sparse. The purpose of this study was to examine if childhood abuse and adversity negatively influences emotional closeness with family in mid- and later life. A second goal was to determine the role of psychosocial resources and personality traits in buffering the effects of early adversities. Gender and cohort differences were explored to see if men were differentially affected than women and whether middle-aged adults (35-49 years old) were differentially affected than older adults (50-74 years old) by the effects of childhood abuse and adversity. Using retrospective accounts of early family abuse and adversities of 1,266 middle aged adults and 1,219 older adults from a large population-based survey, the National Survey of Midlife Development in United States (MIDUS), separate multiple regression analyses were conducted for the two cohorts to examine the effects of childhood emotional and physical abuse and family adversities on perceived emotional closeness with family. Interaction effects between childhood abuse and adversity (e.g., being expelled from school, death of sibling, parental divorce, losing a home to a natural disaster) with psychosocial resources (perceived control and self acceptance), personality characteristics (extraversion and neuroticism), and gender were examined. Results of OLS regressions suggest emotional and physical abuse predicted family closeness in middle-aged adults. Conversely, only emotional abuse predicted family closeness in older adults. Moderation models revealed that high levels of self acceptance were associated with better maintenance of emotional closeness among middle-aged adults who were emotionally and physically abused as children. Older adults with lower extraversion who experienced emotional abuse or reported greater number of adversities in childhood were found to be at higher risk for lower emotional closeness with family. Early life adversities were more detrimental for women. Findings suggest that the aftermath of childhood abuse does not dissipate with time, but continues to influence family relationships in mid- and later life. Identifying the links between childhood adversities and adult relationships can help identify strategic points for intervention to reduce the long-term effects of accumulated adverse experiences over the life course. Published by Elsevier Ltd.

Sexual Outcomes and Satisfaction with Hysterectomy: Influence of Patient Education

PubMed Central

Bradford, Andrea; Meston, Cindy

2010-01-01

Introduction Many women experience improved sexual function after hysterectomy. However, a sizeable minority of women report worsened sexual function after the surgery, and concerns about the effect of surgery on sexual function are common among women planning to undergo hysterectomy. Aim The present study examined the role of education about the potential sexual consequences of hysterectomy in predicting self-reported outcomes and satisfaction with the procedure. Methods We conducted a cross-sectional survey of 204 women who had undergone simple hysterectomy in the preceding 3–12 months. Participants volunteered in response to a Web-based advertisement. Main Outcome Measures Participants indicated their current sexual function using the Female Sexual Function Index (FSFI), and reported positive and negative sexual outcomes experienced after hysterectomy using a checklist. Participants also completed questionnaire items regarding satisfaction with hysterectomy and education from their physicians about sexual risks and benefits prior to surgery. Results Current sexual function scores were related to self-reports of positive and negative sexual outcomes following hysterectomy and overall satisfaction with hysterectomy. Education from a physician about possible adverse sexual outcomes was largely unrelated to self-reports of having experienced those outcomes. However, education about possible negative sexual outcomes predicted overall satisfaction with hysterectomy when controlling for self-reports of positive and negative sexual outcomes. Conclusion Education about potential negative sexual outcomes after surgery may enhance satisfaction with hysterectomy, independent of whether negative sexual outcomes were experienced. Including a discussion of potential sexual changes after surgery may enhance the benefits of presurgical counseling prior to hysterectomy. PMID:17087803

From the Cradle to the Grave: The Effect of Adverse Caregiving Environments on Attachment and Relationships Throughout the Lifespan

PubMed Central

Doyle, Colleen; Cicchetti, Dante

2017-01-01

This paper reviews research examining the effects of adverse early caregiving on relationships throughout the lifespan. Central attachment constructs are summarized and integrated into a review of research on the long-term effects of institutional rearing and child maltreatment. Findings are interpreted within the organizational perspective on development, which conceptualizes attachment as a stage-salient task of infancy that influences the reorganization of adaptive/maladaptive functioning around subsequent stage-salient tasks. Children who experience adverse early caregiving are more likely to exhibit aberrant attachment behaviors, deficits in social-emotional competencies, and persisting difficulties in social functioning and relationship outcomes. Disorganized attachment behavior stemming from adverse early caregiving has been a major focus of this work. Intervention efforts that target mental representations related to attachment relationships can facilitate improved social functioning. Clinical implications of this work are discussed. PMID:28924334

Prospective, longitudinal assessment of quality of life in children from diagnosis to 3 months off treatment for standard risk acute lymphoblastic leukemia: Results of Children's Oncology Group study AALL0331.

PubMed

Mitchell, Hannah-Rose; Lu, Xiaomin; Myers, Regina M; Sung, Lillian; Balsamo, Lyn M; Carroll, William L; Raetz, Elizabeth; Loh, Mignon L; Mattano, Leonard A; Winick, Naomi J; Devidas, Meenakshi; Hunger, Stephen P; Maloney, Kelly; Kadan-Lottick, Nina S

2016-01-15

Standard risk acute lymphoblastic leukemia (SR-ALL) has high cure rates, but requires 2-3 years of therapy. We aimed to (i) prospectively evaluate health-related quality of life (HRQOL) during and after SR-ALL therapy, and (ii) identify associated predictors. Parents of 160 SR-ALL patients enrolled on Children's Oncology Group (COG) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (physical, emotional and social functioning) and Family Assessment Device-General Functioning (FAD-GF) at 1, 6 and 12 months after diagnosis, and 3 months post-therapy. Mean PedsQL scores in physical, emotional and social functioning were impaired 1 month after diagnosis but steadily improved. Three months post-therapy, impaired physical and social functioning was observed in 27.8 and 25.8% of patients, respectively. In repeated-measures analysis, problematic family functioning predicted emotional (OR = 1.85, 95% CI 1.03-3.34) and social (OR = 1.99, 95% CI 1.21-3.27) impairment. Larger household size was associated with social impairment (OR = 1.21, 95% CI 1.02-1.45). Adverse neurological event(s) during therapy predicted post-therapy physical (OR = 5.17, 95% CI 1.61-16.63) and social (OR = 8.17, 95% CI 1.19-56.16) impairment. HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion. In conclusion, children with SR-ALL experience considerable impairment in HRQOL at the end of induction, but rapidly improve. However, many still experience physical and social impairment 3 months post-therapy, suggesting a role for continued family and physical functioning support. Longer follow-up is needed to determine if post-therapy deficits change over time. © 2015 UICC.

Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

PubMed Central

Yao, Jianhua; Jones, Amanda M.; Julien-Williams, Patricia; Stylianou, Mario; Moss, Joel

2014-01-01

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (−2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (−2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (−1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. PMID:25329516

Predicting the clinical efficacy and potential adverse effects of a humanized anticocaine monoclonal antibody

PubMed Central

Norman, Andrew B; Ball, William J

2012-01-01

The effects of a humanized monoclonal antibody (mAb) having high affinity and specificity for cocaine in animal models are reviewed. The mAb reduced the concentration of cocaine in the brain of mice after intravenous injection of cocaine. In addition, the mAb increased the concentration of cocaine required to reinstate cocaine self-administration. These effects may predict clinical efficacy of a passive immunotherapy for reducing the probability of cocaine-induced relapse. However, in the presence of the mAb, once cocaine self-administration was reinstated, the consumption rate of cocaine was increased. This effect is hypothesized to result from a pharmacokinetic/pharmacodynamic interaction. A humanized mAb should minimize adverse events related to the immunogenicity of the mAb protein, and the specificity for cocaine should avoid adverse events related to interactions with physiologically relevant endogenous proteins. PMID:22401638

The Australian experience in dental classification.

PubMed

Mahoney, Greg

2008-01-01

The Australian Defence Health Service uses a disease-risk management strategy to achieve two goals: first, to identify Australian Defence Force (ADF) members who are at high risk of developing an adverse health event, and second, to deliver intervention strategies efficiently so that maximum benefits for health within the ADF are achieved with the least cost. The present dental classification system utilized by the ADF, while an excellent dental triage tool, has been found not to be predictive of an ADF member having an adverse dental event in the following 12-month period. Clearly, there is a need for further research to establish a predictive risk-based dental classification system. This risk assessment must be sensitive enough to accurately estimate the probability that an ADF member will experience dental pain, dysfunction, or other adverse dental events within a forthcoming period, typically 12 months. Furthermore, there needs to be better epidemiological data collected in the field to assist in the research.

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

PubMed

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

Changes in Brain Metabolite Concentrations after Neonatal Hypoxic-ischemic Encephalopathy.

PubMed

Shibasaki, Jun; Aida, Noriko; Morisaki, Naho; Tomiyasu, Moyoko; Nishi, Yuri; Toyoshima, Katsuaki

2018-06-12

Purpose To investigate the time-course changes and predictive utility of brain metabolite concentrations in neonatal hypoxic-ischemic encephalopathy (HIE). Materials and Methods Sixty-eight neonates (age, 35-41 gestational weeks) with HIE were admitted to a neonatal intensive care unit between September 2009 and March 2016 and examined by using proton MR spectroscopy at 18-96 hours (n = 25) and 7-14 days (n = 64) after birth (35-43 postmenstrual weeks) to estimate metabolite concentrations in the deep gray matter. Adverse outcome was defined as death or neurodevelopmental impairment at 18-22 months of age. Areas under the receiver operating characteristic curves were calculated to evaluate the prognostic values of metabolites. Results At 18-96 hours, N-acetylaspartate and creatine concentrations were lower, whereas lactate, and glutamate and glutamine (Glx) concentrations were higher in neonates with adverse outcomes than in those with favorable outcomes. Metabolite concentrations at 18-96 hours decreased during days 7-14 in neonates with adverse outcomes but did not change in those with favorable outcomes. For N-acetylaspartate, creatine, lactate, and Glx concentrations measured at 18-96 hours to predict adverse outcomes, areas under the receiver operating characteristic curve were 0.98, 0.89, 0.96, and 0.88, respectively, whereas at 7-14 days, the areas under the receiver operating characteristic curve were 0.97, 0.97, 0.59, and 0.36, respectively. Conclusion Time-dependent reductions in N-acetylaspartate and creatine concentrations at both 18-96 hours and 7-14 days accurately predicted adverse outcomes. However, higher lactate and glutamate and glutamine concentrations were often transient. © RSNA, 2018 Online supplemental material is available for this article.

Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications.

PubMed

Ghosh, G; Breborowicz, A; Brazert, M; Maczkiewicz, M; Kobelski, M; Dubiel, M; Gudmundsson, S

2006-09-01

Uterine artery Doppler is becoming a routine part of pregnancy surveillance in high-risk pregnancies. Which blood flow velocity waveform index to measure is debated and the 'notch' in early diastole is not widely accepted, as it is a subjective measure. The aim of the present study was to evaluate the different indices in the prediction of adverse outcome of pregnancies suspected for intrauterine fetal growth restriction (IUGR). Uterine artery blood flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance due to suspected IUGR. The median gestational age at examination was 38 weeks (range 25-42 weeks). Only cases having bilateral uterine artery notching were included in the evaluation. The uterine artery Doppler spectrum was analyzed for different indices, including evaluation of notch and end-diastolic velocities. Umbilical artery Doppler velocimetry was also performed. The outcome variables chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and abdominal delivery. ROC-curve calculations were used to compare the different indices. The uterine artery blood velocity pulsatility index (PI) and resistance indices (RI) were the best predictors of adverse outcome of pregnancy. Apart from premature birth, the systolic/end-diastolic ratio was less predictive of adverse outcome. The indices including only diastolic blood velocities were the least predictive of adverse outcome. The group with notch velocity above end-diastolic velocity was compared with those having notch velocity below the end-diastolic velocity. No difference in outcome was seen between the two groups. RI and PI as measures of third trimester utero-placental vascular impedance are the best predictors of adverse outcome of IUGR-suspected pregnancies.

Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse Events.

PubMed

Sailer, Anna M; van Kuijk, Sander M J; Nelemans, Patricia J; Chin, Anne S; Kino, Aya; Huininga, Mark; Schmidt, Johanna; Mistelbauer, Gabriel; Bäumler, Kathrin; Chiu, Peter; Fischbein, Michael P; Dake, Michael D; Miller, D Craig; Schurink, Geert Willem H; Fleischmann, Dominik

2017-04-01

Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable. The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P =0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P =0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P =0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P =0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P =0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%. Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection. © 2017 American Heart Association, Inc.

Modification of the MML turbulence model for adverse pressure gradient flows. M.S. Thesis - Akron Univ., 1993

NASA Technical Reports Server (NTRS)

Conley, Julianne M.

1994-01-01

Computational fluid dynamics is being used increasingly to predict flows for aerospace propulsion applications, yet there is still a need for an easy to use, computationally inexpensive turbulence model capable of accurately predicting a wide range of turbulent flows. The Baldwin-Lomax model is the most widely used algebraic model, even though it has known difficulties calculating flows with strong adverse pressure gradients and large regions of separation. The modified mixing length model (MML) was developed specifically to handle the separation which occurs on airfoils and has given significantly better results than the Baldwin-Lomax model. The success of these calculations warrants further evaluation and development of MML. The objective of this work was to evaluate the performance of MML for zero and adverse pressure gradient flows, and modify it as needed. The Proteus Navier-Stokes code was used for this study and all results were compared with experimental data and with calculations made using the Baldwin-Lomax algebraic model, which is currently available in Proteus. The MML model was first evaluated for zero pressure gradient flow over a flat plate, then modified to produce the proper boundary layer growth. Additional modifications, based on experimental data for three adverse pressure gradient flows, were also implemented. The adapted model, called MMLPG (modified mixing length model for pressure gradient flows), was then evaluated for a typical propulsion flow problem, flow through a transonic diffuser. Three cases were examined: flow with no shock, a weak shock and a strong shock. The results of these calculations indicate that the objectives of this study have been met. Overall, MMLPG is capable of accurately predicting the adverse pressure gradient flows examined in this study, giving generally better agreement with experimental data than the Baldwin-Lomax model.

Outpatient management of low-risk patients with upper gastrointestinal bleeding: can we safely extend the Glasgow Blatchford Score in clinical practice?

PubMed

Mustafa, Zia; Cameron, Allan; Clark, Elaine; Stanley, Adrian J

2015-05-01

The Glasgow Blatchford Score (GBS) is a validated prognostic score for patients presenting with upper gastrointestinal (GI) bleeding (UGIB). The score predicts the need for therapeutic intervention or death, and studies have suggested that outpatient management is safe for patients with a GBS of zero. Our aim was to assess whether we could safely extend the threshold for outpatient management to patients with GBS≤1. Following assessment of our historical data, our UGIB protocol was changed to recommend outpatient management for patients with a GBS≤1, unless required for other reasons. Data on all patients presenting with UGIB over the following 12 months were prospectively recorded, including GBS and clinical Rockall scores. Adverse outcomes were defined by a 30-day combined endpoint of death, endotherapy, interventional radiology, surgery or transfusion. Negative predictive value (NPV) of GBS≤1 for adverse outcomes in UGIB was calculated. A total of 514 patients presented with UGIB in the 12 month study period. Of the patients, 183 (35.6%) had GBS≤1 (111, GBS=0; 72, GBS=1). Of these, 88 (48.1%) were managed as outpatients, and none had an adverse outcome. Of the 95 (51.9%) patients with GBS≤1 managed as inpatients, 80 (84.2%) had comorbidities requiring inpatient care. Within this admitted group with GBS≤1, one patient required transfusion and one died from a nongastrointestinal malignancy. GBS≤1 had an NPV of 99.45% (95% confidence interval 95.53-99.97%) in predicting adverse outcomes within 30 days. GBS≤1 has a high NPV for adverse outcomes in UGIB. This suggests outpatient management of patients with UGIB and that GBS≤1 is safe in our population.

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Applicability of predictive toxicology methods for monoclonal antibody therapeutics: status Quo and scope.

PubMed

Kizhedath, Arathi; Wilkinson, Simon; Glassey, Jarka

2017-04-01

Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few. The advances made in this field are also impeded by a lack of progress in bioprocess development strategies as well as increasing costs owing to attrition, wherein the lack of efficacy and safety accounts for nearly 60 % of all factors contributing to attrition. This reiterates the need for smarter preclinical development using quality by design-based approaches encompassing carefully designed predictive models during early stages of drug development. Different in vitro and in silico methods are extensively used for predicting biological activity as well as toxicity during small molecule drug development; however, their full potential has not been utilized for biological drug development. The scope of in vitro and in silico tools in early developmental stages of monoclonal antibody-based therapeutics production and how it contributes to lower attrition rates leading to faster development of potential drug candidates has been evaluated. The applicability of computational toxicology approaches in this context as well as the pitfalls and promises of extending such techniques to biopharmaceutical development has been highlighted.

Fatty acid amide hydrolase-morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children.

PubMed

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions. In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO 2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use. FAAH genotypes predict risk for morphine-related adverse outcomes.

Gender differences in the effects of childhood adversity on alcohol, drug, and polysubstance-related disorders.

PubMed

Evans, Elizabeth A; Grella, Christine E; Upchurch, Dawn M

2017-07-01

To examine gender differences in the associations between childhood adversity and different types of substance use disorders and whether gender moderates these relationships. We analyzed data from 19,209 women and 13,898 men as provided by Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender moderates the associations between childhood adversity and DSM-IV defined lifetime occurrence of alcohol, drug, and polysubstance-related disorders. We used multinomial logistic regression, weighted to be representative of the US adult civilian, noninstitutionalized population, and we calculated predicted probabilities by gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pair-wise comparisons corrected for multiple comparisons using Bonferroni's method. For each type of substance use disorder, risk was increased by more exposure to childhood adversity, and women had a lower risk than men. However, moderation effects revealed that with more experiences of childhood adversity, the gender gap in predicted probability for a disorder narrowed in relation to alcohol, it converged in relation to drugs such that risk among women surpassed that among men, and it widened in relation to polysubstances. Knowledge regarding substance-specific gender differences associated with childhood adversity exposure can inform evidence-based treatments. It may also be useful for shaping other types of gender-sensitive public health initiatives to ameliorate or prevent different types of substance use disorders.

Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study.

PubMed

Shen, Songying; Lu, Jinhua; Zhang, Lifang; He, Jianrong; Li, Weidong; Chen, Niannian; Wen, Xingxuan; Xiao, Wanqing; Yuan, Mingyang; Qiu, Lan; Cheng, Kar Keung; Xia, Huimin; Mol, Ben Willem J; Qiu, Xiu

2017-02-01

There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22-28weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30-1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1h, and 2h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P=0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1mmol/l), irrespective of 1h or 2h glucose levels. A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A Study of the Solar Wind-Magnetosphere Coupling Using Neural Networks

NASA Astrophysics Data System (ADS)

Wu, Jian-Guo; Lundstedt, Henrik

1996-12-01

The interaction between solar wind plasma and interplanetary magnetic field (IMF) and Earth's magnetosphere induces geomagnetic activity. Geomagnetic storms can cause many adverse effects on technical systems in space and on the Earth. It is therefore of great significance to accurately predict geomagnetic activity so as to minimize the amount of disruption to these operational systems and to allow them to work as efficiently as possible. Dynamic neural networks are powerful in modeling the dynamics encoded in time series of data. In this study, we use partially recurrent neural networks to study the solar wind-magnetosphere coupling by predicting geomagnetic storms (as measured by the Dstindex) from solar wind measurements. The solar wind, the IMF and the geomagnetic index Dst data are hourly averaged and read from the National Space Science Data Center's OMNI database. We selected these data from the period 1963 to 1992, which cover 10552h and contain storm time periods 9552h and quiet time periods 1000h. The data are then categorized into three data sets: a training set (6634h), across-validation set (1962h), and a test set (1956h). The validation set is used to determine where the training should be stopped whereas the test set is used for neural networks to get the generalization capability (the out-of-sample performance). Based on the correlation analysis between the Dst index and various solar wind parameters (including various combinations of solar wind parameters), the best coupling functions can be found from the out-of-sample performance of trained neural networks. The coupling functions found are then used to forecast geomagnetic storms one to several hours in advance. The comparisons are made on iterating the single-step prediction several times and on making a non iterated, direct prediction. Thus, we will present the best solar wind-magnetosphere coupling functions and the corresponding prediction results. Interesting Links: Lund Space Weather and AI Center

Modeling mixtures of thyroid gland function disruptors in a vertebrate alternative model, the zebrafish eleutheroembryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thienpont, Benedicte; Barata, Carlos; Raldúa, Demetrio, E-mail: drpqam@cid.csic.es

2013-06-01

Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable alternative model for screening chemicals impairing the thyroid hormone synthesis. The present study usedmore » the intrafollicular T4-content (IT4C) of zebrafish eleutheroembryos as integrative endpoint for testing the hypotheses that the effect of mixtures of TGFDs with a similar mode of action [inhibition of thyroid peroxidase (TPO)] was well predicted by a concentration addition concept (CA) model, whereas the response addition concept (RA) model predicted better the effect of dissimilarly acting binary mixtures of TGFDs [TPO-inhibitors and sodium-iodide symporter (NIS)-inhibitors]. However, CA model provided better prediction of joint effects than RA in five out of the six tested mixtures. The exception being the mixture MMI (TPO-inhibitor)-KClO{sub 4} (NIS-inhibitor) dosed at a fixed ratio of EC{sub 10} that provided similar CA and RA predictions and hence it was difficult to get any conclusive result. There results support the phenomenological similarity criterion stating that the concept of concentration addition could be extended to mixture constituents having common apical endpoints or common adverse outcomes. - Highlights: • Potential synergic or additive effect of mixtures of chemicals on thyroid function. • Zebrafish as alternative model for testing the effect of mixtures of goitrogens. • Concentration addition seems to predict better the effect of mixtures of goitrogens.« less

Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis.

PubMed

Morris, R Katie; Bilagi, Ashwini; Devani, Pooja; Kilby, Mark D

2017-03-01

To determine association, and predictive ability, of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) with adverse pregnancy outcomes. Searches of Medline, Embase and CINAHL (inception September 2015) for studies including pregnant women with first trimester PAPP-A and assessment of pregnancy outcomes. Study characteristics, quality and results extracted. Meta-analysis of odds ratios (ORs), and likelihood ratios (LRs) and 95% confidence intervals (CI). Thirty-two studies including 175 240 pregnancies. PAPP-A <5th centile had a moderate association with: birth weight <10th centile OR 2.08 (95% CI 1.89-2.29), <5th centile OR 2.83 (95% CI 2.52-3.18); pre-eclampsia OR 1.94 (95% CI 1.63-2.30), preterm birth <37 weeks OR 2.09 (95% CI 1.87-2.33), and composite adverse outcome OR 3.31 (95% CI 1.80-5.11). The predictive ability was poor: Birth weight <10th centile LR + ve 1.96 (95% CI 1.58-2.43), LR-ve 0.93 (95% CI 0.89-0.98); birth weight <5th centile LR + ve 2.65 (95% CI 2.35-2.99), LR-ve 0.85 (95% CI 0.74-0.98); PTB <37 weeks LR + ve 1.84 (95% CI 1.41-2.39), LR-ve 0.92 (95% CI 0.87-0.98). First trimester low maternal serum PAPP-A is associated with adverse pregnancy outcome, but predictive values are poor. Further work should address PAPP-A as a continuous variable in combination with other prognostic markers as a prediction model. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Psychological resilience is associated with more intact social functioning in veterans with post-traumatic stress disorder and depression.

PubMed

Wingo, Aliza P; Briscione, Maria; Norrholm, Seth D; Jovanovic, Tanja; McCullough, S Ashley; Skelton, Kelly; Bradley, Bekh

2017-03-01

Patients with depression or post-traumatic stress disorder (PTSD), common sequelae among individuals exposed to stressful or traumatic events, often report impairment in social functioning. Resilience is a multidimensional construct that enables adaptive coping with life adversity. Relationship between resilience and social functioning among veterans with depression and PTSD is not entirely clear and is the focus of this report. Resilience was assessed in 264 veterans using the Connor-Davidson Resilience Scale, PTSD with the PTSD Symptom Scale, depression with the Beck Depression Inventory, and social functioning with the Short Form Health Survey. Higher resilience was associated with more intact social functioning after PTSD and depression severity, childhood maltreatment, physical health, gender, education, marital status, and employment were simultaneously adjusted for. Childhood maltreatment, gender, marital status, education, and employment did not predict social functioning; however, greater severity of PTSD, depression, or physical health problems was each significantly associated with more impaired social functioning. Our findings suggest that higher resilience was associated with more intact social functioning regardless of the severity of PTSD and depression. Given the importance of social functioning in depression and/or PTSD recovery, studies are needed to examine if enhancing resilience presents a complementary approach to alleviating impaired social functioning. Published by Elsevier B.V.

Body mass index and depressive symptoms in older adults: the moderating roles of race, sex, and socioeconomic status.

PubMed

Sachs-Ericsson, Natalie; Burns, Andrea B; Gordon, Kathryn H; Eckel, Lisa A; Wonderlich, Steven A; Crosby, Ross D; Blazer, Dan G

2007-09-01

Although the long-term health risks associated with obesity in older adults have been well documented, less is known about the psychological consequences. The current study examined the relationship between body mass index (BMI) and subsequent depressive symptoms. The authors anticipated that BMI would predict depressive symptoms, and that this relationship would be greater among women, individuals of higher socioeconomic status (SES), and white subjects. A three-year longitudinal epidemiological design was employed. Participants were obtained from a biracial sample of community-dwelling older adults (N = 2,406) and were interviewed in their home by trained interviewers. A comprehensive survey assessed age, gender, race, SES (education and income), and health functioning variables. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. BMI was derived from self-reported weight and height. BMI was found to predict depressive symptoms. Contrary to predictions, the influence of BMI on depressive symptoms was greater for African Americans than whites and, in particular, African Americans with less education. There were no sex differences. Among older adults, BMI was associated with depressive symptoms although the effect size was small. Factors contributing to this relationship may differ from those observed in younger populations, for example, health functioning may play a larger role. Obesity appears to have the most adverse impact on those who are most likely to be overweight, lower SES African Americans.

Contributions of local speech encoding and functional connectivity to audio-visual speech perception

PubMed Central

Giordano, Bruno L; Ince, Robin A A; Gross, Joachim; Schyns, Philippe G; Panzeri, Stefano; Kayser, Christoph

2017-01-01

Seeing a speaker’s face enhances speech intelligibility in adverse environments. We investigated the underlying network mechanisms by quantifying local speech representations and directed connectivity in MEG data obtained while human participants listened to speech of varying acoustic SNR and visual context. During high acoustic SNR speech encoding by temporally entrained brain activity was strong in temporal and inferior frontal cortex, while during low SNR strong entrainment emerged in premotor and superior frontal cortex. These changes in local encoding were accompanied by changes in directed connectivity along the ventral stream and the auditory-premotor axis. Importantly, the behavioral benefit arising from seeing the speaker’s face was not predicted by changes in local encoding but rather by enhanced functional connectivity between temporal and inferior frontal cortex. Our results demonstrate a role of auditory-frontal interactions in visual speech representations and suggest that functional connectivity along the ventral pathway facilitates speech comprehension in multisensory environments. DOI: http://dx.doi.org/10.7554/eLife.24763.001 PMID:28590903

The N-Methyl-D-Aspartate Receptor in Heart Development: A Gene Knockdown Model Using siRNA

PubMed Central

Lie, Octavian V.; Bennett, Gregory D.; Rosenquist, Thomas H

2009-01-01

Antagonists of the N-methyl-D-aspartate receptor (NMDAR) may disrupt the development of the cardiac neural crest (CNC) and contribute to conotruncal heart defects. To test this interaction, a loss-of-function model was generated using small interfering RNAs (siRNA) directed against the critical NR1-subunit of this receptor in avian embryos. The coding sequence of the chicken NR1-gene and predicted protein sequences were characterized and found to be homologous with other vertebrate species. Analysis of its spatiotemporal expression demonstrated its expression within the neural tube at pre-migratory CNC sites. siRNA targeted to the NR1-mRNA in pre-migratory CNC lead to a significant decrease in NR1 protein expression. However, embryo survival and heart development were not adversely affected. These results indicate that the CNC may function normally in the absence of functional NMDAR, and that NMDAR antagonists may have a complex impact upon the CNC that transcends impairment of a single receptor type. PMID:19737608

AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

EPA Science Inventory

Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

Application of Knowledge Discovery in Databases Methodologies for Predictive Models for Pregnancy Adverse Events

ERIC Educational Resources Information Center

Taft, Laritza M.

2010-01-01

In its report "To Err is Human", The Institute of Medicine recommended the implementation of internal and external voluntary and mandatory automatic reporting systems to increase detection of adverse events. Knowledge Discovery in Databases (KDD) allows the detection of patterns and trends that would be hidden or less detectable if analyzed by…

Application of Near Infrared Spectroscopy, Intravascular Ultrasound and the Coronary Calcium Score to Predict Adverse Coronary Events

DTIC Science & Technology

2012-10-01

hospitalization 9. Emergence of rhythm disturbances requiring treatment 10. Development of acute coronary syndrome 11. Cerebrovascular accident Adverse...catheterization. These will include coronary injury including dissection, perforation or occlusion, death, cerebrovascular accident , myocardial... cerebrovascular accident , bleeding, infection, arrhythmia, access site damage, coronary dissection, coronary thrombosis and myocardial infarction, among

Comparison of in vitro and ex vivo thyroid hormone synthesis inhibition results and in vivo outcomes for a series of benzothiazoles

EPA Science Inventory

Assessing how in vitro data may be used to predict adverse effects in vivo is critical as efforts are advanced to incorporate in vitro assays into a risk assessment framework. Within the context of a thyroid hormone (TH) synthesis inhibition adverse outcome pathway (AOP), in vitr...

Defence mechanisms: the role of physiology in current and future environmental protection paradigms

PubMed Central

Glover, Chris N

2018-01-01

Abstract Ecological risk assessments principally rely on simplified metrics of organismal sensitivity that do not consider mechanism or biological traits. As such, they are unable to adequately extrapolate from standard laboratory tests to real-world settings, and largely fail to account for the diversity of organisms and environmental variables that occur in natural environments. However, an understanding of how stressors influence organism health can compensate for these limitations. Mechanistic knowledge can be used to account for species differences in basal biological function and variability in environmental factors, including spatial and temporal changes in the chemical, physical and biological milieu. Consequently, physiological understanding of biological function, and how this is altered by stressor exposure, can facilitate proactive, predictive risk assessment. In this perspective article, existing frameworks that utilize physiological knowledge (e.g. biotic ligand models, adverse outcomes pathways and mechanistic effect models), are outlined, and specific examples of how mechanistic understanding has been used to predict risk are highlighted. Future research approaches and data needs for extending the incorporation of physiological information into ecological risk assessments are discussed. Although the review focuses on chemical toxicants in aquatic systems, physical and biological stressors and terrestrial environments are also briefly considered. PMID:29564135

The stressful (and not so stressful) nature of language brokering: identifying when brokering functions as a cultural stressor for Latino immigrant children in early adolescence.

PubMed

Kam, Jennifer A; Lazarevic, Vanja

2014-12-01

Language brokering remains prevalent among immigrant families, but it is widely assumed that brokering functions as a cultural stressor, resulting in adverse health outcomes for immigrant youth. Few studies, however, have tested this assumption, particularly while using longitudinal data and capturing multiple dimensions of brokering. Thus, this study examined how depressive symptoms and family-based acculturation stress mediated the relationships between various aspects of brokering (i.e., frequency of brokering, positive and negative feelings about brokering, brokering norms, and brokering efficacy) and alcohol, cigarette, and marijuana use and other risky behaviors. Using longitudinal survey data from 234 Latino early adolescents in 6th-8th grades (M age  = 12.4 years; Females = 46.2 %), brokering for parents indirectly affected alcohol and marijuana use through family-based acculturation stress; however, these significant indirect effects became non-significant when taking into account negative brokering feelings and brokering as a burden on one's time. Feeling positively or efficacious about brokering or having pro-brokering norms did not directly predict any adverse mental and behavioral health outcomes. Moderation analyses, however, revealed that brokering for parents did not seem to function as a stressor when Latino early adolescents were high in brokering efficacy (e.g., feeling confident in one's ability to broker) or descriptive brokering norms (e.g., perceiving one's peers as brokering often). By contrast, when Latino early adolescents perceived brokering as a burden, brokering for parents functioned as a stressor, placing Latino early adolescents at risk for family-based acculturation stress, and in turn, alcohol and marijuana use. Such findings point to the complexity of brokering.

Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.

PubMed

Abrahamowicz, Michal; Bartlett, Gillian; Tamblyn, Robyn; du Berger, Roxane

2006-04-01

Accurate assessment of medication impact requires modeling cumulative effects of exposure duration and dose; however, postmarketing studies usually represent medication exposure by baseline or current use only. We propose new methods for modeling various aspects of medication use history and employment of them to assess the adverse effects of selected benzodiazepines. Time-dependent measures of cumulative dose or duration of use, with weighting of past exposures by recency, were proposed. These measures were then included in alternative versions of the multivariable Cox model to analyze the risk of fall related injuries among the elderly new users of three benzodiazepines (nitrazepam, temazepam, and flurazepam) in Quebec. Akaike's information criterion (AIC) was used to select the most predictive model for a given benzodiazepine. The best-fitting model included a combination of cumulative duration and current dose for temazepam, and cumulative dose for flurazepam and nitrazepam, with different weighting functions. The window of clinically relevant exposure was shorter for flurazepam than for the two other products. Careful modeling of the medication exposure history may enhance our understanding of the mechanisms underlying their adverse effects.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

PubMed

Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

2015-01-01

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

PubMed

Miller, Shefali; McTeague, Lisa M; Gyurak, Anett; Patenaude, Brian; Williams, Leanne M; Grieve, Stuart M; Korgaonkar, Mayuresh S; Etkin, Amit

2015-08-01

Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients. Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes. © 2015 Wiley Periodicals, Inc.

Enantiomer specific measurements of current-use pesticides in aquatic systems

EPA Science Inventory

Contrary to predictions, current-use pesticides are adversely affecting aquatic systems in both urban and agricultural watersheds, particularly in California. One possible divergence from fate and effect predictions is that some current-use pesticides are chiral molecules. Increa...

Cardiovascular outcomes of a positive nuclear stress test but negative coronary angiography in a multiethnic male predominant cohort.

PubMed

Addison, Daniel; Singh, Vinita; Okyere-Asante, K; Okafor, Henry

2014-01-01

Patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging (MPI), but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma. They are often dismissed as having 'false-positive MPI'. Moreover, a majority of the available long-term outcome data for it has been derived from homogenous female populations. In this study, we sought to evaluate the long-term outcomes of this presentation in a multiethnic male-predominant cohort. We retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on MPI, but with no significant angiographic disease on subsequent cardiac catheterization (cases). The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute myocardial infarction and stroke) post-index coronary angiogram was tracked. Similar data was collected for 37 patients who also presented with chest pain, but normal MPI over the same period (controls). Overall average follow-up was over 22 months. Fifty-three percent (26/47) of the cases had one or more of the adverse outcomes as compared with 22% (8/37) of controls (P < 0.01). Of these, 13 (50.0%) and 3 (37.5%) were males, respectively. Ischemia on MPI is predictive of long-term adverse cardiovascular outcomes despite normal ('false-negative') coronary angiography. This appears to be gender-neutral.

75 FR 38521 - Registration Review; Biopesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...

75 FR 60117 - Registration Review; Biopesticides Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

77 FR 74479 - Registration Review; Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... function without unreasonable adverse effects on human health or the environment. Registration review...

Comparative Approaches to Understanding the Relation Between Aging and Physical Function.

PubMed

Justice, Jamie N; Cesari, Matteo; Seals, Douglas R; Shively, Carol A; Carter, Christy S

2016-10-01

Despite dedicated efforts to identify interventions to delay aging, most promising interventions yielding dramatic life-span extension in animal models of aging are often ineffective when translated to clinical trials. This may be due to differences in primary outcomes between species and difficulties in determining the optimal clinical trial paradigms for translation. Measures of physical function, including brief standardized testing batteries, are currently being proposed as biomarkers of aging in humans, are predictive of adverse health events, disability, and mortality, and are commonly used as functional outcomes for clinical trials. Motor outcomes are now being incorporated into preclinical testing, a positive step toward enhancing our ability to translate aging interventions to clinical trials. To further these efforts, we begin a discussion of physical function and disability assessment across species, with special emphasis on mice, rats, monkeys, and man. By understanding how physical function is assessed in humans, we can tailor measurements in animals to better model those outcomes to establish effective, standardized translational functional assessments with aging. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Does Low PAPP-A Predict Adverse Placenta-Mediated Outcomes in a Low-Risk Nulliparous Population? the Great Obstetrical Syndromes (GOS) Study.

PubMed

Boutin, Amélie; Gasse, Cédric; Demers, Suzanne; Blanchet, Geneviève; Giguère, Yves; Bujold, Emmanuel

2018-06-01

First-trimester low concentration of pregnancy-associated plasma protein A (PAPP-A) has been associated with adverse perinatal outcomes in high-risk populations. This study aimed to estimate the ability of PAPP-A to identify adverse outcomes in a low-risk population. The study investigators recruited nulliparous women with singleton pregnancy at their 11-13-week ultrasound scan. Serum samples were collected, and maternal PAPP-A concentration was measured using the B⋅R⋅A⋅H⋅M⋅S PAPP-A KRYPTOR (ThermoFisher Scientific, Hennigsdorf, Germany) automated assay. PAPP-A was reported in multiple of median (MoM) adjusted for GA. Participants were followed until delivery for pregnancy outcomes including preeclampsia (PE), SGA <3rd percentile, and fetal death. Receiver operating characteristic curves with the area under the curve (AUC) were used to evaluate the predictive value of PAPP-A. The investigators calculated the detection rates (DRs) and positive predictive values (PPVs) of a PAPP-A < 0.4 MoM. The study investigators recruited 4739 eligible participants at a mean GA of 13 ± 6 weeks. The investigators observed 232 (4.9%) cases of PE, 84 (1.8%) cases of SGA, and 14 (0.3%) fetal deaths. PAPP-A was moderately associated with PE (AUC 0.57; 95% CI 0.53-0.61) and SGA (AUC 0.62; 95% CI 0.56-0.69), but not with fetal death (AUC 0.43; 95% CI 0.23-0.63). PAPP-A < 0.4 MoM was observed in 364 (7.7%) participants and had poor predictive values for PE (DR 9.8%; PPV 6.3%), SGA (DR 18.1%; PPV 4.4%), and fetal death (DR 21.4%; PPV 0.9%). Isolated first trimester PAPP-A has a limited predictive value for adverse pregnancy outcomes (other than trisomies). Low PAPP-A (<0.4 MoM) should be used in combination with other markers for the prediction of PE, SGA, or fetal death, and it does not constitute an indication for low-dose aspirin. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Early Adversity, Psychopathology, and Latent Class Profiles of Global Physical Health From Preschool Through Early Adolescence.

PubMed

Whalen, Diana J; Belden, Andy C; Tillman, Rebecca; Barch, Deanna M; Luby, Joan L

The purpose of the present report was to describe the longitudinal trajectories of physical health beginning during preschool and continuing into early adolescence; explore whether these trajectories were predicted by psychosocial adversity, family income-to-needs ratio, and psychiatric disorders occurring during the preschool period; and determine whether psychiatric disorders mediated these relations. Participants included 296 children participating in a longitudinal study of early-onset psychopathology spanning 10 years. Semistructured clinical interviews were conducted with caregivers to determine children's psychiatric diagnoses between ages 3 and 6 years. Caregivers also completed annual assessments of their child's physical health problems (ages 3-13) and reported on the family's income and indicators of psychosocial adversity. Growth mixture modeling revealed 2 trajectories of physical health problems: a stable, low group (n = 199) and a high, increasing group (n = 57) indicating linear increases in physical health problems from ages 3 to 13. Preschool psychiatric diagnoses (Estimate [Est] = 0.05, p < .001), family income-to-needs ratio (Est = -0.01, p = .012), and psychosocial adversity (Est = 0.02, p = .015) predicted membership in the high, increasing trajectory of physical health problems. Early-onset psychopathology mediated relations between psychosocial adversity and physical health problems (αβ = 0.31, p = .050) and between income-to-needs ratio and physical health problems (αβ = -0.29, p < .021). These findings indicate the importance of early indicators of risk: low income-to-needs ratios, high psychosocial adversity, and psychiatric disorders occurring during the preschool period for contributing to increasing physical health problems from preschool through early adolescence. Early-onset psychiatric disorders also mediated relations between psychosocial adversity, income-to-needs ratio, and physical health problems.

Early adversity, psychopathology, and latent class profiles of global physical health from preschool through early adolescence

PubMed Central

Whalen, Diana J.; Belden, Andy C.; Tillman, Rebecca; Barch, Deanna M.; Luby, Joan L.

2016-01-01

Objective The purpose of the present report was to describe the longitudinal trajectories of physical health beginning during preschool and continuing into early adolescence, explore whether these trajectories were predicted by psychosocial adversity, family income-to-needs ratio, and psychiatric disorders occurring during the preschool period, and determine whether psychiatric disorders mediated these relations. Methods Participants included 296 children participating in a longitudinal study of early-onset psychopathology spanning ten years. Semi-structured clinical interviews were conducted with caregivers to determine children’s psychiatric diagnoses between ages 3–6. Caregivers also completed annual assessments of their child’s physical health problems (ages 3–13), as well as reported on the family’s income and indicators of psychosocial adversity. Results Growth mixture modeling revealed two trajectories of physical health problems: a stable, low group (n = 199) and a high, increasing group (n = 57) indicating linear increases in physical health problems from ages 3–13. Preschool psychiatric diagnoses (Est= 0.05, p<.001), family income-to-needs ratio (Est= −0.01, p=.012), and psychosocial adversity (Est=0.02, p=.015) predicted membership in the high, increasing trajectory of physical health problems. Early-onset psychopathology mediated relations between psychosocial adversity and physical health problems (αβ= 0.31, p=.050) and between income-to-needs ratio and physical health problems (αβ= −0.29, p<.021). Conclusions These findings indicate the importance of early indicators of risk: low income-to-needs ratios, high psychosocial adversity, and psychiatric disorders occurring during the preschool period for contributing to increasing physical health problems from preschool through early adolescence. Early-onset psychiatric disorders also mediated relations between psychosocial adversity, income-to-needs ratio, and physical health problems. PMID:27749744

Approaches to predicting potential impacts of climate change on forest disease: an example with Armillaria root disease

Treesearch

Ned B. Klopfenstein; Mee-Sook Kim; John W. Hanna; Bryce A. Richardson; John E. Lundquist

2009-01-01

Predicting climate change influences on forest diseases will foster forest management practices that minimize adverse impacts of diseases. Precise locations of accurately identified pathogens and hosts must be documented and spatially referenced to determine which climatic factors influence species distribution. With this information, bioclimatic models can predict the...

Assessment of the temperature cut-off point by a commercial intravaginal device to predict parturition in piedmontese beef cows

USDA-ARS?s Scientific Manuscript database

Dystocic parturitions have an adverse impact on animal productivity, and therefore the profitability of the farm. In this regard, an accurate calving prediction is essential since it allows for efficient and prompt assistance for the dam and the calf. Numerous approaches to predict parturition have ...

Using human genetics to predict the effects and side-effects of drugs.

PubMed

Stender, Stefan; Tybjærg-Hansen, Anne

2016-04-01

'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. LDL cholesterol lowering variants in HMG-Coenzyme A reductase and Niemann-Pick C1-like protein 1, the targets for statins and ezetimibe, protect against ischemic heart disease (IHD). However, HMG-Coenzyme A reductase and Niemann-Pick C1-Like Protein 1-variants also increase the risk of type 2 diabetes and gallstone disease, respectively. Mutations in proprotein convertase subtilisin kexin 9 (PCSK9), apolipoprotein B, and microsomal triglyceride transfer protein cause low LDL cholesterol and protect against IHD. In addition, mutations in apolipoprotein B and microsomal triglyceride transfer protein cause hepatic steatosis, in concordance with drugs that inhibit these targets. Both mutations in PCSK9 and PCSK9-inhibition seem without adverse effects. Mutations in APOC3 cause low triglycerides and protect against IHD, and recent pharmacological APOC3-inhibition reported major reductions in plasma triglycerides. Human genetics support that low lipoprotein(a) protects against IHD, without adverse effects, and the first trial of lipoprotein(a) inhibition reduced lipoprotein(a) up to 78%. Recent genetic studies have confirmed the efficacy of statins and ezetimibe in protecting against IHD. Results from human genetics support that several lipid-lowering drugs currently under development are likely to prove efficacious in protecting against IHD, without major adverse effects.

Machine Learning to Predict, Detect, and Intervene Older Adults Vulnerable for Adverse Drug Events in the Emergency Department.

PubMed

Ouchi, Kei; Lindvall, Charlotta; Chai, Peter R; Boyer, Edward W

2018-06-01

Adverse drug events (ADEs) are common and have serious consequences in older adults. ED visits are opportunities to identify and alter the course of such vulnerable patients. Current practice, however, is limited by inaccurate reporting of medication list, time-consuming medication reconciliation, and poor ADE assessment. This manuscript describes a novel approach to predict, detect, and intervene vulnerable older adults at risk of ADE using machine learning. Toxicologists' expertise in ADE is essential to creating the machine learning algorithm. Leveraging the existing electronic health records to better capture older adults at risk of ADE in the ED may improve their care.

Machine Learning for Social Services: A Study of Prenatal Case Management in Illinois.

PubMed

Pan, Ian; Nolan, Laura B; Brown, Rashida R; Khan, Romana; van der Boor, Paul; Harris, Daniel G; Ghani, Rayid

2017-06-01

To evaluate the positive predictive value of machine learning algorithms for early assessment of adverse birth risk among pregnant women as a means of improving the allocation of social services. We used administrative data for 6457 women collected by the Illinois Department of Human Services from July 2014 to May 2015 to develop a machine learning model for adverse birth prediction and improve upon the existing paper-based risk assessment. We compared different models and determined the strongest predictors of adverse birth outcomes using positive predictive value as the metric for selection. Machine learning algorithms performed similarly, outperforming the current paper-based risk assessment by up to 36%; a refined paper-based assessment outperformed the current assessment by up to 22%. We estimate that these improvements will allow 100 to 170 additional high-risk pregnant women screened for program eligibility each year to receive services that would have otherwise been unobtainable. Our analysis exhibits the potential for machine learning to move government agencies toward a more data-informed approach to evaluating risk and providing social services. Overall, such efforts will improve the efficiency of allocating resource-intensive interventions.

New Factors Predicting Delayed Graft Function: a Multi-Center Cohort Study of Kidney Donation After Brain Death Followed by Circulatory Death.

PubMed

Sun, Qipeng; Huang, Zhengyu; Zhou, Honglan; Lin, Minzhuan; Hua, Xuefeng; Hong, Liangqing; Na, Ning; Cai, Ruiming; Wang, Gang; Sun, Qiquan

2018-05-30

Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice. © 2018 The Author(s). Published by S. Karger AG, Basel.

The Protective Role of the Family and Social Support Network in a Sample of HIV-Positive African American Women: Results of a Pilot Study

PubMed Central

Robbins, Michael; Szapocznik, José; Tejeda, Manuel; Samuels, Deanne; Ironson, Gail; Antoni, Michael

2005-01-01

This study examined the role of family functioning and social support in protecting HIV-positive African American women from the adverse psychological consequences associated with deterioration in their CD4 cell count. Participants were 38 African American HIV-positive women who had recently given birth. Results demonstrated that changes in CD4 cell counts were inversely predictive of psychological distress and were moderated by family functioning and social support satisfaction. Women with good family functioning were less affected by changes in their CD4 cell counts, and women with poor family functioning were more emotionally responsive to changes in CD4 cell count. Unexpectedly, women from families where conflicts tended to be clearly laid out and discussed were also more responsive to both changes in CD4 cell counts. Interventions are recommended that increase a client’s social support satisfaction, foster an adaptive level of connectedness to family, and enhance the family’s range of conflict resolution styles. PMID:16609750

Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report.

PubMed

Reneman, L; Majoie, C B; Schmand, B; van den Brink, W; den Heeten, G J

2001-10-01

3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy") is known to damage brain serotonin neurons in animals and possibly humans. Because serotonergic damage may adversely affect memory, we compared verbal memory function between MDMA users and MDMA-naïve control subjects and evaluated the relationship between verbal memory function and neuronal dysfunction in the MDMA users. An auditory verbal memory task (Rey Auditory Verbal Learning Test) was used to study eight abstinent MDMA users and seven control subjects. In addition 1H-MRS was used in different brain regions of all MDMA users to measure N-acetylaspartate/creatine (NAA/Cr) ratios, a marker for neuronal viability. The MDMA users recalled significantly fewer words than control subjects on delayed (p =.03) but not immediate recall (p =.08). In MDMA users, delayed memory function was strongly associated with NAA/Cr only in the prefrontal cortex (R(2) =.76, p =.01). Greater decrements in memory function predicted lower NAA/Cr levels-and by inference greater neuronal dysfunction-in the prefrontal cortex of MDMA users.

Male scarcity is associated with higher prevalence of premature gestation and low birth weight births across the United States.

PubMed

Kruger, Daniel J; Clark, Jillian; Vanas, Sarah

2013-01-01

Modern adverse birth outcomes may partially result from mechanisms evolved to evaluate environmental conditions and regulate maternal investment trade-offs. Male scarcity in a population is associated with a cluster of characteristics related to higher mating effort and lower paternal investment. We predicted that modern populations with male scarcity would have shorter gestational times and lower birth weights on average. We compared US Centers for Disease Control and Prevention county-aggregated year 2000 birth records with US Decennial Census data. We combined these data in a path model with the degree of male scarcity and known socio-economic predictors of birth outcomes as exogenous predictors of prematurity and low birth weight, with single mother households as a proportion of families with children as a mediator (N = 450). Male scarcity was directly associated with higher rates of low birth weight. Male scarcity made significant indirect predictions of rates of prematurity and low birth weight, as mediated by the proportion of families headed by single mothers. Aggregate socio-economic status also indirectly predicted birth outcomes, as mediated by the proportion of families headed by single mothers, whereas the proportion African American retained both direct and indirect predictions of adverse birth outcomes. Male scarcity influences life history tradeoffs, with consequences for important social and public health issues such as adverse birth outcomes. Copyright © 2013 Wiley Periodicals, Inc.

77 FR 40048 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

77 FR 18810 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... its intended function without unreasonable adverse effects on human health or the environment...

75 FR 35810 - Registration Review; Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-23

... disproportionately high and adverse human health impacts or environmental effects from exposure to the pesticides... can still be used without unreasonable adverse effects on human health or the environment. A pesticide... function without unreasonable adverse effects on human health or the environment. Registration review...

75 FR 60119 - Registration Review; Antimicrobial Pesticide Dockets Opened for Review and Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... disproportionately high and adverse human health impacts or environmental effects from exposure to the pesticides... can still be used without unreasonable adverse effects on human health or the environment. A pesticide... its intended function without unreasonable adverse effects on human health or the environment...

76 FR 38166 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... adverse human health impacts or environmental effects from exposure to the pesticides discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...

Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure

PubMed Central

Costanzo, Maria Rosa; Ronco, Claudio; Abraham, William T.; Agostoni, Piergiuseppe; Barasch, Jonathan; Fonarow, Gregg C.; Gottlieb, Stephen S.; Jaski, Brian E.; Kazory, Amir; Levin, Allison P.; Levin, Howard R.; Marenzi, Giancarlo; Mullens, Wilfried; Negoianu, Dan; Redfield, Margaret M.; Tang, W.H. Wilson; Testani, Jeffrey M.; Voors, Adriaan A.

2017-01-01

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients’ vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration. PMID:28494980

Added clinical value of applying myocardial deformation imaging to assess right ventricular function.

PubMed

Sokalskis, Vladislavs; Peluso, Diletta; Jagodzinski, Annika; Sinning, Christoph

2017-06-01

Right heart dysfunction has been found to be a strong prognostic factor predicting adverse outcome in various cardiopulmonary diseases. Conventional echocardiographic measurements can be limited by geometrical assumptions and impaired reproducibility. Speckle tracking-derived strain provides a robust quantification of right ventricular function. It explicitly evaluates myocardial deformation, as opposed to tissue Doppler-derived strain, which is computed from tissue velocity gradients. Right ventricular longitudinal strain provides a sensitive tool for detecting right ventricular dysfunction, even at subclinical levels. Moreover, the longitudinal strain can be applied for prognostic stratification of patients with pulmonary hypertension, pulmonary embolism, and congestive heart failure. Speckle tracking-derived right atrial strain, right ventricular longitudinal strain-derived mechanical dyssynchrony, and three-dimensional echocardiography-derived strain are emerging imaging parameters and methods. Their application in research is paving the way for their clinical use. © 2017, Wiley Periodicals, Inc.

Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays

PubMed Central

Rampersad, Sephra N.

2012-01-01

Accurate prediction of the adverse effects of test compounds on living systems, detection of toxic thresholds, and expansion of experimental data sets to include multiple toxicity end-point analysis are required for any robust screening regime. Alamar Blue is an important redox indicator that is used to evaluate metabolic function and cellular health. The Alamar Blue bioassay has been utilized over the past 50 years to assess cell viability and cytotoxicity in a range of biological and environmental systems and in a number of cell types including bacteria, yeast, fungi, protozoa and cultured mammalian and piscine cells. It offers several advantages over other metabolic indicators and other cytotoxicity assays. However, as with any bioassay, suitability must be determined for each application and cell model. This review seeks to highlight many of the important considerations involved in assay use and design in addition to the potential pitfalls. PMID:23112716

Body composition, muscle capacity, and physical function in older adults: an integrated conceptual model.

PubMed

Brady, Anne O; Straight, Chad R; Evans, Ellen M

2014-07-01

The aging process leads to adverse changes in body composition (increases in fat mass and decreases in skeletal muscle mass), declines in physical function (PF), and ultimately increased risk for disability and loss of independence. Specific components of body composition or muscle capacity (strength and power) may be useful in predicting PF; however, findings have been mixed regarding the most salient predictor of PF. The development of a conceptual model potentially aids in understanding the interrelated factors contributing to PF with the factors of interest being physical activity, body composition, and muscle capacity. This article also highlights sex differences in these domains. Finally, factors known to affect PF, such as sleep, depression, fatigue, and self-efficacy, are discussed. Development of a comprehensive conceptual model is needed to better characterize the most salient factors contributing to PF and to subsequently inform the development of interventions to reduce physical disability in older adults.

Multiscale modeling and simulation of embryogenesis for in silico predictive toxicology (WC9)

EPA Science Inventory

Translating big data from alternative and HTS platforms into hazard identification and risk assessment is an important need for predictive toxicology and for elucidating adverse outcome pathways (AOPs) in developmental toxicity. Understanding how chemical disruption of molecular ...

Biogenic volatile organic compounds in the Earth system.

PubMed

Laothawornkitkul, Jullada; Taylor, Jane E; Paul, Nigel D; Hewitt, C Nicholas

2009-01-01

Biogenic volatile organic compounds produced by plants are involved in plant growth, development, reproduction and defence. They also function as communication media within plant communities, between plants and between plants and insects. Because of the high chemical reactivity of many of these compounds, coupled with their large mass emission rates from vegetation into the atmosphere, they have significant effects on the chemical composition and physical characteristics of the atmosphere. Hence, biogenic volatile organic compounds mediate the relationship between the biosphere and the atmosphere. Alteration of this relationship by anthropogenically driven changes to the environment, including global climate change, may perturb these interactions and may lead to adverse and hard-to-predict consequences for the Earth system.

Ego strengths, racial/ethnic identity, and well-being among North American Indian/First Nations adolescents.

PubMed

Gfellner, Barbara

2016-01-01

This study investigated associations between ego strengths (psychosocial development), racial/ethnic identity using Multi-Ethnic Identity Measure-Revised (exploration, commitment) and Multidimensional Measure of Racial Identity (centrality, private regard, public regard) dimensions, and personal adjustment/well-being among 178 North American Indian/First Nations adolescents who resided and attended school on reserves. As predicted, ego strengths related directly with centrality, private regard, and the adjustment measures; the moderation of ego strengths for exploration, commitment, and private regard reflected adverse functioning for those with less than advanced ego strengths. As well, ego strengths mediated associations between centrality and private regard with several measures of personal well-being. Practical and theoretical implications are considered.

Lifestyle changes of Japanese people on overseas assignment in Michigan, USA.

PubMed

Kitamura, Kazuya; Fetters, Michael D; Sano, Kiyoshi; Sato, Juichi; Ban, Nobutaro

2009-07-16

Temporary work assignments in the United States (US) are widely considered to have negative health outcomes on Asians mostly due to adverse changes in diet and exercise, though there is little research on this phenomenon. This study investigated the impact of lifestyle changes on the biological and psychological health and health behaviours of Japanese people on temporary assignments in the US. In this cross sectional survey, we distributed a 38 item self-administered questionnaire addressing health habits, mental health function, lifestyle changes and dietary habits to adult Japanese patients presenting for general physicals at a family medicine clinic serving Japanese patients. We conducted simple statistics and regression analysis between length of stay and other health outcomes to determine whether length of residence in the US was predictive of negative lifestyle changes. Most participants reported increased caloric intake, weight gain, and less exercise. They also reported increased time with family. More women than men reported physical symptoms and anxiety related to stress. Smoking and alcohol intake were essentially unchanged. No associations were identified between length of residence in the US and health lifestyle habits or other health outcomes. Negative lifestyle changes occur in diet and exercise for overseas Japanese people, but a positive change in increased family time was found. Women appear to be at a greater risk for somatic disorders than men. As duration of stay does not appear predictive of adverse changes, clinicians should advise patients going abroad of these risks regardless of the term of the work assignment.

Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

PubMed

Huang, Bao-Tao; Peng, Yong; Liu, Wei; Zhang, Chen; Huang, Fang-Yang; Wang, Peng-Ju; Zuo, Zhi-Liang; Liao, Yan-Biao; Chai, Hua; Li, Qiao; Zhao, Zhen-Gang; Luo, Xiao-Lin; Ren, Xin; Huang, Kai-Sen; Meng, Qing-Tao; Chen, Chi; Huang, De-Jia; Chen, Mao

2015-03-01

Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.

Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis

PubMed Central

Powell, J; Kitchen, N; Heslin, J; Greenwood, R

2002-01-01

Objectives: To investigate (1) the prevalence of various aspects of cognitive and psychosocial dysfunction, including post-traumatic stress symptoms, over nine months after subarachnoid haemorrhage (SAH); (2) whether SAH is preceded by increased life stress; (3) to what extent adverse outcomes may be predicted from preillness life stress, early neurological impairment, age, and sex; and (4) relations between emotional and functional outcomes. Methods: 52 patients with good neurological recovery after surgery for SAH were each matched for age, sex, and occupation with a healthy control participant. SAH patients were assessed three and nine months postdischarge on measures of cognitive functioning, mood, and social functioning. Objective stressors and subjective life change during the preceding year were rated retrospectively. Controls completed measures of mood and social functioning once only. Results: Compared with controls, SAH patients showed increased mood disturbance, subtle cognitive impairment, and abnormally low independence and participation on measures of social functioning. 60% showed clinically significant post-traumatic stress symptomatology (intrusive thoughts or avoidance of reminders) at three months and 30% at nine months. Independence in activities of daily living was greatly reduced in half to a third of the sample at both three and nine months. Productive employment was below the 10th percentile of the control group for 75% of patients at three months and for 56% at nine months; this outcome could not be predicted from selected demographic, premorbid, or clinical variables but dependence on others for organisational activities was predicted by impaired prose recall. Mood at nine months was strongly predicted by prior mental health problems, poor physical health, dysphasia, and impaired prose recall at three months. There was no evidence of an abnormally high level of stressful life events in the year before SAH, although patients rated their subjective level of stress in this period slightly more highly than did the control participants. Conclusions: These findings highlight the need for structured support and treatment after surgery for SAH to reduce persisting mood disturbance and increase independence and participation. PMID:12023423

Functional outcome instruments used for cervical spondylotic myelopathy: interscale correlation and prediction of preference-based quality of life.

PubMed

Whitmore, Robert G; Ghogawala, Zoher; Petrov, Dmitriy; Schwartz, J Sanford; Stein, Sherman C

2013-08-01

There is limited literature comparing different functional outcome measures used for cervical spondylotic myelopathy (CSM). To determine the correlation among five functional outcome measures used in CSM patient assessment and their ability to predict preference-based quality of life (QOL). Prospective observational study. Patients, aged 40 to 85 years, with CSM and cervical spinal cord compression at two or more levels from degenerative spondylosis were enrolled from seven sites over a 2-year period. The modified Japanese Orthopedic Association scale, Oswestry neck disability index (Oswestry NDI or Oswestry), Nurick scale, norm-based short-form 36 physical component summary, and EuroQol-5D (EQ-5D) were collected. The Jean and David Wallace foundation provided funding for this study. Cervical spondylotic myelopathy patients undergoing either anterior or posterior surgery were prospectively followed with five different functional outcome measures over 1 year. Correlations among scales were tested using the Spearman rank correlation test. The sensitivity and specificity of each scale for predicting the global index of the EQ-5D were determined, and receiver-operating characteristic analysis was used to compare each scale's ability to discriminate QOL. A total of 106 patients were initially enrolled; 103 were operated on for CSM and followed for 1 year. Their ages ranged from 40 to 82 years (mean 61.9), and 61.3% were men. Correlations among the various functional outcome instruments were all highly significant (p<.001), but the degree of correlation varied greatly. Correlation between the EQ-5D scale and the Nurick scale was the least (Spearman rho 0.5539); correlation was the highest with the Oswestry NDI (Spearman rho 0.8306). The Oswestry NDI also had the greatest ability to discriminate favorable from adverse QOL compared with the other outcome instruments (p=.023). Preference-based quality-of-life instruments, such as the EQ-5D, are important measures for studying spinal disorders. Among the various commonly used outcome instruments for CSM, the Oswestry NDI is the most predictive of preference-based QOL. Copyright © 2013 Elsevier Inc. All rights reserved.

Cumulative burden of lifetime adversities: Trauma and mental health in low-SES African Americans and Latino/as.

PubMed

Myers, Hector F; Wyatt, Gail E; Ullman, Jodie B; Loeb, Tamra B; Chin, Dorothy; Prause, Nicole; Zhang, Muyu; Williams, John K; Slavich, George M; Liu, Honghu

2015-05-01

This study examined the utility of a lifetime cumulative adversities and trauma model in predicting the severity of mental health symptoms of depression, anxiety, and posttraumatic stress disorder. We also tested whether ethnicity and gender moderate the effects of this stress exposure construct on mental health using multigroup structural equation modeling. A sample of 500 low-socioeconomic status African American and Latino men and women with histories of adversities and trauma were recruited and assessed with a standard battery of self-report measures of stress and mental health. Multiple-group structural equation models indicated good overall model fit. As hypothesized, experiences of discrimination, childhood family adversities, childhood sexual abuse, other childhood trauma, and chronic stresses all loaded on the latent cumulative burden of adversities and trauma construct (CBAT). The CBAT stress exposure index in turn predicted the mental health status latent variable. Although there were several significant univariate ethnic and gender differences, and ethnic and gender differences were observed on several paths, there were no significant ethnic differences in the final model fit of the data. These findings highlight the deleterious consequences of cumulative stress and trauma for mental health and underscore a need to assess these constructs in selecting appropriate clinical interventions for reducing mental health disparities and improving human health. (c) 2015 APA, all rights reserved).

Prediction of outcome in asphyxiated newborns treated with hypothermia: Is a MRI scoring system described before the cooling era still useful?

PubMed

Al Amrani, Fatema; Marcovitz, Jaclyn; Sanon, Priscille-Nice; Khairy, May; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

2018-05-01

To determine whether an MRI scoring system, which was validated in the pre-cooling era, can still predict the neurodevelopmental outcome of asphyxiated newborns treated with hypothermia at 2 years of age. We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. An MRI scoring system, which was validated in the pre-cooling era, was used to grade the severity of brain injury on the neonatal brain MRI. Their neurodevelopment was assessed around 2 years of age; adverse outcome included cerebral palsy, global developmental delay, and/or epilepsy. One hundred and sixty-nine newborns were included. Among the 131 newborns who survived and had a brain MRI during the neonatal period, 92% were evaluated around 2 years of age or later. Of these newborns, 37% displayed brain injury, and 23% developed an adverse outcome. Asphyxiated newborns treated with hypothermia who had an adverse outcome had a significantly higher MRI score (p <0.001) compared to those without an adverse outcome. An MRI scoring system that was validated before the cooling era is still able to reliably differentiate which of the asphyxiated newborns treated with hypothermia were more prone to develop an adverse outcome around 2 years of age. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

PubMed

Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

2017-11-01

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatty acid amide hydrolase–morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children

PubMed Central

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Aim: Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid–endocannabinoid interactions. Patients & methods: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. Results: We found significant FAAH–morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH–HCVR association predicts risk of impending RD from morphine use. Conclusion: FAAH genotypes predict risk for morphine-related adverse outcomes. PMID:27977335

Risk prediction models for major adverse cardiac event (MACE) following percutaneous coronary intervention (PCI): A review

NASA Astrophysics Data System (ADS)

Manan, Norhafizah A.; Abidin, Basir

2015-02-01

Five percent of patients who went through Percutaneous Coronary Intervention (PCI) experienced Major Adverse Cardiac Events (MACE) after PCI procedure. Risk prediction of MACE following a PCI procedure therefore is helpful. This work describes a review of such prediction models currently in use. Literature search was done on PubMed and SCOPUS database. Thirty literatures were found but only 4 studies were chosen based on the data used, design, and outcome of the study. Particular emphasis was given and commented on the study design, population, sample size, modeling method, predictors, outcomes, discrimination and calibration of the model. All the models had acceptable discrimination ability (C-statistics >0.7) and good calibration (Hosmer-Lameshow P-value >0.05). Most common model used was multivariate logistic regression and most popular predictor was age.

Biological Relevance of Key Events (KE) in utero in The Androgen Adverse Outcome Pathway Network (AOPn) to Adverse Effects in F1 Male Rats

EPA Science Inventory

We are conducting studies to evaluate the biological relevance of changes in KEs and molecular initiating events (MIE) in AOPs to determine if these can accurately predict of the dose levels of chemicals that disrupt the androgen signaling pathway in utero. Herein, we focus on ch...

Beyond Climate and Weather Science: Expanding the Forecasting Family to Serve Societal Needs

NASA Astrophysics Data System (ADS)

Barron, E. J.

2009-05-01

The ability to "anticipate" the future is what makes information from the Earth sciences valuable to society - whether it is the prediction of severe weather or the future availability of water resources in response to climate change. An improved ability to anticipate or forecast has the potential to serve society by simultaneously improving our ability to (1) promote economic vitality, (2) enable environmental stewardship, (3) protect life and property, as well as (4) improve our fundamental knowledge of the earth system. The potential is enormous, yet many appear ready to move quickly toward specific mitigation and adaptation strategies assuming that the science is settled. Five important weakness must be addressed first: (1) the formation of a true "climate services" function and capability, (2) the deliberate investment in expanding the family of forecasting elements to incorporate a broader array of environmental factors and impacts, (3) the investment in the sciences that connect climate to society, (4) a deliberate focus on the problems associated with scale, in particular the difference between the scale of predictive models and the scale associated with societal decisions, and (5) the evolution from climate services and model predictions to the equivalent of "environmental intelligence centers." The objective is to bring the discipline of forecasting to a broader array of environmental challenges. Assessments of the potential impacts of global climate change on societal sectors such as water, human health, and agriculture provide good examples of this challenge. We have the potential to move from a largely reactive mode in addressing adverse health outcomes, for example, to one in which the ties between climate, land cover, infectious disease vectors, and human health are used to forecast and predict adverse human health conditions. The potential exists for a revolution in forecasting, that entrains a much broader set of societal needs and solutions. The argument is made that (for example) the current capabilities in the prediction of environmental health is similar to the capabilities (and potential) of weather forecasting in the 1960's.

Testing an explanatory model of nurses' intention to report adverse drug reactions in hospital settings.

PubMed

Angelis, Alessia De; Pancani, Luca; Steca, Patrizia; Colaceci, Sofia; Giusti, Angela; Tibaldi, Laura; Alvaro, Rosaria; Ausili, Davide; Vellone, Ercole

2017-05-01

To test an explanatory model of nurses' intention to report adverse drug reactions in hospital settings, based on the theory of planned behaviour. Under-reporting of adverse drug reactions is an important problem among nurses. A cross-sectional design was used. Data were collected with the adverse drug reporting nurses' questionnaire. Confirmatory factor analysis was performed to test the factor validity of the adverse drug reporting nurses' questionnaire, and structural equation modelling was used to test the explanatory model. The convenience sample comprised 500 Italian hospital nurses (mean age = 43.52). Confirmatory factor analysis supported the factor validity of the adverse drug reporting nurses' questionnaire. The structural equation modelling showed a good fit with the data. Nurses' intention to report adverse drug reactions was significantly predicted by attitudes, subjective norms and perceived behavioural control (R² = 0.16). The theory of planned behaviour effectively explained the mechanisms behind nurses' intention to report adverse drug reactions, showing how several factors come into play. In a scenario of organisational empowerment towards adverse drug reaction reporting, the major predictors of the intention to report are support for the decision to report adverse drug reactions from other health care practitioners, perceptions about the value of adverse drug reaction reporting and nurses' favourable self-assessment of their adverse drug reaction reporting skills. © 2017 John Wiley & Sons Ltd.

Life adversity is associated with smoking relapse after a quit attempt.

PubMed

Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

2016-09-01

Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Timely Diagnosis of Acute Kidney Injury Using Kinetic eGFR and the Creatinine Excretion to Production Ratio, E/eG - Creatinine Can Be Useful!

PubMed

Endre, Zoltán H; Pianta, Timothy J; Pickering, John W

2016-01-01

Post transplant repeated measurements of urine volume and serum creatinine (sCr) are used to assess kidney function. Under non-steady state conditions, repeated measurement of sCr allows calculation of the kinetic estimated GFR (KeGFR). Additional measurement of urinary creatinine allows the calculation of the creatinine excretion to (estimated) production ratio (E/eG). We hypothesized that post-transplant KeGFR and E/eG would predict delayed graft function (DGF), as early as 4 h and outperform a validated clinical model at 12 h. This was a retrospective analysis of prospectively acquired data in a study of 56 recipients of deceased-donor kidney transplant. We assessed predictive performance with the area under the receiver operator characteristic curve (AUC) and the added value to a clinical model with integrated discrimination improvement analysis. At 4 h, the AUC for E/eG was 0.87 (95% CI 0.77-0.96) and for KeGFR 0.69 (95% CI 0.56-0.83). Both E/eG and KeGFR improved the risk prediction of a clinical model for DGF by 32 and 18%, and for non-DGF by 17 and 10%, respectively. While E/eG had better predictive performance of DGF than KeGFR, KeGFR might also facilitate perioperative management including drug dosing after kidney transplantation. Together these measurements may facilitate the possibility of conducting trials of early intervention to ameliorate the adverse effects of ischaemia-reperfusion injury on long-term DGF. © 2016 S. Karger AG, Basel.

An antenatal prediction model for adverse birth outcomes in an urban population: The contribution of medical and non-medical risks.

PubMed

Posthumus, A G; Birnie, E; van Veen, M J; Steegers, E A P; Bonsel, G J

2016-07-01

in the Netherlands the perinatal mortality rate is high compared to other European countries. Around eighty percent of perinatal mortality cases is preceded by being small for gestational age (SGA), preterm birth and/or having a low Apgar-score at 5 minutes after birth. Current risk detection in pregnancy focusses primarily on medical risks. However, non-medical risk factors may be relevant too. Both non-medical and medical risk factors are incorporated in the Rotterdam Reproductive Risk Reduction (R4U) scorecard. We investigated the associations between R4U risk factors and preterm birth, SGA and a low Apgar score. a prospective cohort study under routine practice conditions. six midwifery practices and two hospitals in Rotterdam, the Netherlands. 836 pregnant women. the R4U scorecard was filled out at the booking visit. after birth, the follow-up data on pregnancy outcomes were collected. Multivariate logistic regression was used to fit models for the prediction of any adverse outcome (preterm birth, SGA and/or a low Apgar score), stratified for ethnicity and socio-economic status (SES). factors predicting any adverse outcome for Western women were smoking during the first trimester and over-the-counter medication. For non-Western women risk factors were teenage pregnancy, advanced maternal age and an obstetric history of SGA. Risk factors for high SES women were low family income, no daily intake of vegetables and a history of preterm birth. For low SES women risk factors appeared to be low family income, non-Western ethnicity, smoking during the first trimester and a history of SGA. the presence of both medical and non-medical risk factors early in pregnancy predict the occurrence of adverse outcomes at birth. Furthermore the risk profiles for adverse outcomes differed according to SES and ethnicity. to optimise effective risk selection, both medical and non-medical risk factors should be taken into account in midwifery and obstetric care at the booking visit. Copyright © 2016. Published by Elsevier Ltd.

Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

ERIC Educational Resources Information Center

Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

2008-01-01

Purpose: Researchers know little about the physical performance ability of residential care/assisted living (RC/AL) residents and its relationship to adverse outcomes such as fracture, nursing home placement, functional decline, and death. The purposes of this article are to (a) describe the functional characteristics of RC/AL residents, (b)…

Mothers' Adverse Childhood Experiences and Negative Parenting Behaviors: Connecting Mothers' Difficult Pasts to Present Parenting Behavior via Reflective Functioning

ERIC Educational Resources Information Center

Kolomeyer, Ellen; Renk, Kimberly; Cunningham, Annelise; Lowell, Amanda; Khan, Maria

2016-01-01

Previous studies have supported a connection between adverse childhood experiences (ACEs) and negative outcomes in adulthood. Fewer studies have examined the connection between ACEs and parenting behaviors, however. The study described in this article examined the relationships among ACEs, reflective functioning, and negative parenting behaviors…

Correlates of adverse childhood experiences among adults with severe mood disorders.

PubMed

Lu, Weili; Mueser, Kim T; Rosenberg, Stanley D; Jankowski, Mary Kay

2008-09-01

Adverse childhood experiences have been found to be associated with poor physical and poor mental health, impaired functioning, and increased substance abuse in the general adult population. The purpose of this study was to examine the clinical correlates of these experiences among adults with severe mood disorders. Adverse childhood experiences (including physical abuse, sexual abuse, parental mental illness, loss of parent, parental separation or divorce, witnessing domestic violence, and placement in foster or kinship care) were assessed retrospectively in a sample of 254 adults with major mood disorders. The relationships between cumulative exposure to these experiences and psychiatric problems, health, substance use disorders, community functioning, trauma exposure in adulthood, and high-risk behaviors were examined. Increased exposure to childhood adverse experiences was related to high-risk behaviors, diagnosis of a substance use disorder, exposure to trauma in adulthood, psychiatric problems (younger age at first hospitalization, number of suicide attempts, and diagnosis of posttraumatic stress disorder), medical service utilization, and homelessness. The findings extend research in the general population by suggesting that adverse childhood experiences contribute to worse mental and physical health and functional outcomes among adults with severe mood disorders.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

PubMed

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

The Predictive Validity of the Short-Term Assessment of Risk and Treatability (START) for Multiple Adverse Outcomes in a Secure Psychiatric Inpatient Setting.

PubMed

O'Shea, Laura E; Picchioni, Marco M; Dickens, Geoffrey L

2016-04-01

The Short-Term Assessment of Risk and Treatability (START) aims to assist mental health practitioners to estimate an individual's short-term risk for a range of adverse outcomes via structured consideration of their risk ("Vulnerabilities") and protective factors ("Strengths") in 20 areas. It has demonstrated predictive validity for aggression but this is less established for other outcomes. We collated START assessments for N = 200 adults in a secure mental health hospital and ascertained 3-month risk event incidence using the START Outcomes Scale. The specific risk estimates, which are the tool developers' suggested method of overall assessment, predicted aggression, self-harm/suicidality, and victimization, and had incremental validity over the Strength and Vulnerability scales for these outcomes. The Strength scale had incremental validity over the Vulnerability scale for aggressive outcomes; therefore, consideration of protective factors had demonstrable value in their prediction. Further evidence is required to support use of the START for the full range of outcomes it aims to predict. © The Author(s) 2015.

Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions.

PubMed

Luo, Heng; Fokoue-Nkoutche, Achille; Singh, Nalini; Yang, Lun; Hu, Jianying; Zhang, Ping

2018-05-23

Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available. We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs. These models obtain an overall area under the receiver operating characteristic curve (AUROC) of 0.843 and an overall area under the precision-recall curve (AUPR) of 0.395, outperforming seven structural fingerprint-based prediction models. Using the method, we predicted skin striae for fluticasone propionate, dermatitis acneiform for mometasone, and decreased libido for irinotecan, as demonstrations. Furthermore, we analyzed the top binding proteins associated with some of the ADRs, which can help to understand and/or generate hypotheses for underlying mechanisms of ADRs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhancing the Functional Content of Eukaryotic Protein Interaction Networks

PubMed Central

Pandey, Gaurav; Arora, Sonali; Manocha, Sahil; Whalen, Sean

2014-01-01

Protein interaction networks are a promising type of data for studying complex biological systems. However, despite the rich information embedded in these networks, these networks face important data quality challenges of noise and incompleteness that adversely affect the results obtained from their analysis. Here, we apply a robust measure of local network structure called common neighborhood similarity (CNS) to address these challenges. Although several CNS measures have been proposed in the literature, an understanding of their relative efficacies for the analysis of interaction networks has been lacking. We follow the framework of graph transformation to convert the given interaction network into a transformed network corresponding to a variety of CNS measures evaluated. The effectiveness of each measure is then estimated by comparing the quality of protein function predictions obtained from its corresponding transformed network with those from the original network. Using a large set of human and fly protein interactions, and a set of over GO terms for both, we find that several of the transformed networks produce more accurate predictions than those obtained from the original network. In particular, the measure and other continuous CNS measures perform well this task, especially for large networks. Further investigation reveals that the two major factors contributing to this improvement are the abilities of CNS measures to prune out noisy edges and enhance functional coherence in the transformed networks. PMID:25275489

Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van

Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzedmore » to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the optic radiation is a critical radiosensitive structure.« less

Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.

PubMed

Shinohara, Satoshi; Uchida, Yuzo; Kasai, Mayuko; Sunami, Rei

2017-08-01

To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

PubMed

Kostrubiec, Maciej; Łabyk, Andrzej; Pedowska-Włoszek, Justyna; Pacho, Szymon; Dzikowska-Diduch, Olga; Dul, Przemysław; Ciurzyński, Michał; Bienias, Piotr; Pruszczyk, Piotr

2012-09-01

Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Platelet density per monocyte predicts adverse events in patients after percutaneous coronary intervention.

PubMed

Rutten, Bert; Roest, Mark; McClellan, Elizabeth A; Sels, Jan W; Stubbs, Andrew; Jukema, J Wouter; Doevendans, Pieter A; Waltenberger, Johannes; van Zonneveld, Anton-Jan; Pasterkamp, Gerard; De Groot, Philip G; Hoefer, Imo E

2016-01-01

Monocyte recruitment to damaged endothelium is enhanced by platelet binding to monocytes and contributes to vascular repair. Therefore, we studied whether the number of platelets per monocyte affects the recurrence of adverse events in patients after percutaneous coronary intervention (PCI). Platelet-monocytes complexes with high and low median fluorescence intensities (MFI) of the platelet marker CD42b were isolated using cell sorting. Microscopic analysis revealed that a high platelet marker MFI on monocytes corresponded with a high platelet density per monocyte while a low platelet marker MFI corresponded with a low platelet density per monocyte (3.4 ± 0.7 vs 1.4 ± 0.1 platelets per monocyte, P=0.01). Using real-time video microscopy, we observed increased recruitment of high platelet density monocytes to endothelial cells as compared with low platelet density monocytes (P=0.01). Next, we classified PCI scheduled patients (N=263) into groups with high, medium and low platelet densities per monocyte and assessed the recurrence of adverse events. After multivariate adjustment for potential confounders, we observed a 2.5-fold reduction in the recurrence of adverse events in patients with a high platelet density per monocyte as compared with a low platelet density per monocyte [hazard ratio=0.4 (95% confidence interval, 0.2-0.8), P=0.01]. We show that a high platelet density per monocyte increases monocyte recruitment to endothelial cells and predicts a reduction in the recurrence of adverse events in patients after PCI. These findings may imply that a high platelet density per monocyte protects against recurrence of adverse events.

Validating new summary indices for the Childhood Trauma Interview: associations with first onsets of major depressive disorder and anxiety disorders.

PubMed

Vrshek-Schallhorn, Suzanne; Wolitzky-Taylor, Kate; Doane, Leah D; Epstein, Alyssa; Sumner, Jennifer A; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Isaia, Ashley; Hammen, Constance; Adam, Emma K

2014-09-01

Childhood and adolescent adversity is of great interest in relation to risk for psychopathology, and interview measures of adversity are thought to be more reliable and valid than their questionnaire counterparts. One interview measure, the Childhood Trauma Interview (CTI; Fink et al., 1995), has been positively evaluated relative to similar measures, but there are some psychometric limitations to an existing scoring approach that limit the full potential of this measure. We propose several new summary indices for the CTI that permit examination of different types of adversity and different developmental periods. Our approach creates several summary indices: one sums the severity scores of adversities endorsed; another utilizes the number of minor and major (moderate to severe) adversities. The new indices were examined in association with first onsets of major depressive disorder (MDD) and anxiety disorders across a 5-year period using annual clinical diagnostic interviews (Structured Clinical Interview for DSM-IV-TR). Summary scores derived with the previously used approach were also examined for comparison. Data on 332 participants came from the Youth Emotion Project, a longitudinal study of risk for emotional disorders. Results support the predictive validity of the proposed summary scoring methods and indicate that several forms of major (but typically not minor) adversity are significantly associated with first onsets of MDD and anxiety disorders. Finally, multivariate regression models show that, in many instances, the new indices contributed significant unique variance predicting disorder onsets over and above the previously used summary indices. PsycINFO Database Record (c) 2014 APA, all rights reserved.

A Vision and Strategy:Predictive Ecotoxicology in the 21st Century

EPA Science Inventory

The manuscript provides an introduction and overview for a series of five papers resulting from a SETAC Pellston Workshop titled A Vision and Strategy for Predictive Ecotoxicology in the 21st Century: Defining Adverse Outcome Pathways Associated with Ecological Risk. It proposes...

Disrupted Executive Function and Aggression in Individuals With a History of Adverse Childhood Experiences: An Event-Related Potential Study.

PubMed

Xue, Jiao-Mei; Lin, Ping-Zhen; Sun, Ji-Wei; Cao, Feng-Lin

2017-12-01

Here, we explored the functional and neural mechanisms underlying aggression related to adverse childhood experiences. We assessed behavioral performance and event-related potentials during a go/no-go and N-back paradigm. The participants were 15 individuals with adverse childhood experiences and high aggression (ACE + HA), 13 individuals with high aggression (HA), and 14 individuals with low aggression and no adverse childhood experiences (control group). The P2 latency (initial perceptual processing) was longer in the ACE + HA group for the go trials. The HA group had a larger N2 (response inhibition) than controls for the no-go trials. Error-related negativity (error processing) in the ACE + HA and HA groups was smaller than that of controls for false alarm go trials. Lastly, the ACE + HA group had shorter error-related negativity latencies than controls for false alarm trials. Overall, our results reveal the neural correlates of executive function in aggressive individuals with ACEs.

Predictive Risk Modelling to Prevent Child Maltreatment and Other Adverse Outcomes for Service Users: Inside the ‘Black Box’ of Machine Learning

PubMed Central

Gillingham, Philip

2016-01-01

Recent developments in digital technology have facilitated the recording and retrieval of administrative data from multiple sources about children and their families. Combined with new ways to mine such data using algorithms which can ‘learn’, it has been claimed that it is possible to develop tools that can predict which individual children within a population are most likely to be maltreated. The proposed benefit is that interventions can then be targeted to the most vulnerable children and their families to prevent maltreatment from occurring. As expertise in predictive modelling increases, the approach may also be applied in other areas of social work to predict and prevent adverse outcomes for vulnerable service users. In this article, a glimpse inside the ‘black box’ of predictive tools is provided to demonstrate how their development for use in social work may not be straightforward, given the nature of the data recorded about service users and service activity. The development of predictive risk modelling (PRM) in New Zealand is focused on as an example as it may be the first such tool to be applied as part of ongoing reforms to child protection services. PMID:27559213

Predictive Risk Modelling to Prevent Child Maltreatment and Other Adverse Outcomes for Service Users: Inside the 'Black Box' of Machine Learning.

PubMed

Gillingham, Philip

2016-06-01

Recent developments in digital technology have facilitated the recording and retrieval of administrative data from multiple sources about children and their families. Combined with new ways to mine such data using algorithms which can 'learn', it has been claimed that it is possible to develop tools that can predict which individual children within a population are most likely to be maltreated. The proposed benefit is that interventions can then be targeted to the most vulnerable children and their families to prevent maltreatment from occurring. As expertise in predictive modelling increases, the approach may also be applied in other areas of social work to predict and prevent adverse outcomes for vulnerable service users. In this article, a glimpse inside the 'black box' of predictive tools is provided to demonstrate how their development for use in social work may not be straightforward, given the nature of the data recorded about service users and service activity. The development of predictive risk modelling (PRM) in New Zealand is focused on as an example as it may be the first such tool to be applied as part of ongoing reforms to child protection services.

Identifying Predictors of Resilience in Students

ERIC Educational Resources Information Center

Edwards, T.; Catling, J. C.; Parry, E.

2016-01-01

Adverse life experiences have been linked with a wide range of negative outcomes. However, despite being exposed to adversity, individuals who exhibit high levels of resilience appear to be less impacted by adversity, and continue to function normally. Using self-report measures and a sample of 161 participants aged between 16 and 21, the present…

75 FR 80496 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-22

... high and adverse human health impacts or environmental effects from exposure to the pesticide(s... can still be used without unreasonable adverse effects on human health or the environment. A pesticide... perform its intended function without unreasonable adverse effects on human health or the environment...

78 FR 18586 - Registration Review; Pesticide Dockets Opened for Review and Comment and Other Docket Acts

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... adverse human health impacts or environmental effects from exposure to the pesticide(s) discussed in this... without unreasonable adverse effects on human health or the environment. A pesticide's registration review... perform its intended function without unreasonable adverse effects on human health or the environment...

Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease.

PubMed

Kuhlman, Kate Ryan; Chiang, Jessica J; Horn, Sarah; Bower, Julienne E

2017-09-01

Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential adverse effects of omega-3 Fatty acids in dogs and cats.

PubMed

Lenox, C E; Bauer, J E

2013-01-01

Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Inflammatory Mediators Drive Adverse Right Ventricular Remodeling and Dysfunction and Serve as Potential Biomarkers.

PubMed

Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S; Weissmann, Norbert; Ghofrani, Hossein A; Schermuly, Ralph T

2018-01-01

Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function.

Inflammatory Mediators Drive Adverse Right Ventricular Remodeling and Dysfunction and Serve as Potential Biomarkers

PubMed Central

Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S.; Weissmann, Norbert; Ghofrani, Hossein A.; Schermuly, Ralph T.

2018-01-01

Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function. PMID:29875701

Unmet Health Services Needs Among US Children with Developmental Disabilities: Associations with Family Impact and Child Functioning.

PubMed

Lindly, Olivia J; Chavez, Alison E; Zuckerman, Katharine E

To determine associations of unmet needs for child or family health services with (1) adverse family financial and employment impacts and (2) child behavioral functioning problems among US children with autism spectrum disorder (ASD), developmental delay (DD), and/or intellectual disability (ID). This was a secondary analysis of parent-reported data from the 2009 to 2010 National Survey of Children with Special Health Care Needs linked to the 2011 Survey of Pathways to Diagnosis and Services. The study sample (n = 3,518) represented an estimated 1,803,112 US children aged 6 to 17 years with current ASD, DD, and/or ID (developmental disabilities). Dependent variables included adverse family financial and employment impacts, as well as child behavioral functioning problems. The independent variables of interest were unmet need for (1) child health services and (2) family health services. Multivariable logistic regression models were fit to examine associations. Unmet need for child and family health services, adverse family financial and employment impacts, and child behavioral functioning problems were prevalent among US children with developmental disabilities. Unmet needs were associated with an increased likelihood of adverse family employment and financial impacts. Unmet needs were associated with an increased likelihood of child behavioral functioning problems the following year; however, this association was not statistically significant. Unmet needs are associated with adverse impacts for children with developmental disabilities and their families. Increased access to and coordination of needed health services following ASD, DD, and/or ID diagnosis may improve outcomes for children with developmental disabilities and their families.

Fine Particulate Matter and Cardiovascular Disease: Comparison of Assessment Methods for Long-term Exposure

EPA Science Inventory

Background Adverse cardiovascular events have been linked with PM2.5 exposure obtained primarily from air quality monitors, which rarely co-locate with participant residences. Modeled PM2.5 predictions at finer resolution may more accurately predict residential exposure; however...

Do Childhood Adversities Predict Suicidality? Findings from the General Population of the Metropolitan Area of São Paulo, Brazil.

PubMed

Coêlho, Bruno Mendonça; Andrade, Laura Helena; Borges, Guilherme; Santana, Geilson Lima; Viana, Maria Carmen; Wang, Yuan-Pang

2016-01-01

Childhood adversities have been associated with a number of medical and psychiatric outcomes. However, the reported effects that specific childhood adversities have on suicidality vary across studies. This was a cross-sectional, stratified, multistage area probability investigation of a general population in Brazil, designated the São Paulo Megacity Mental Health Survey. The World Mental Health Composite International Diagnostic Interview was applied in 5037 individuals ≥ 18 years of age, in order to assess 12 different adversities occurring during childhood and/or adolescence, as well as to look for associations between those adversities and subsequent suicidality in different age strata. Over half of the respondents reported at least one childhood adversity. Only physical abuse was consistently associated with suicide attempts in all subsequent life stages (OR = 2.1). Among adults 20-29 years of age, the likelihood of a suicide attempt was correlated with parental divorce, whereas suicidal ideation was associated with prior sexual abuse. Among adults over 30 years of age, physical illness and economic adversity emerged as relevant childhood adversities associated with suicide attempts, whereas sexual abuse, family violence, and economic adversity were associated with suicidal ideation. Childhood adversities, especially physical abuse, are likely associated with unfavorable consequences in subsequent years. For suicidality across a lifespan, the role of different childhood adversities must be examined independently.