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1.  Influence of Perceived Parent and Peer Endorsement on Adolescent Smoking Intentions: Parents Have More Say, But Their Influence Wanes as Kids Get Older 
PLoS ONE  2014;9(7):e101275.
Purpose
The aim of the study is to investigate how adolescents' perception of parents' and peers' smoking approval influences adolescent smoking intention, and how age affects this influence in a Swiss sample of adolescents. To know the influence of age can help to develop specific prevention programs tailored to the age groups needs.
Method
in a cross sectional survey, students aged between 11 and 14 from public and private middle schools in the Italian region of Switzerland (Ticino) answered questions on smoking habits, parents' and peers' approval and intention to smoke.
Results
peers' and parents' approval significantly influence students' smoking intention, and students' age significantly moderates this relation: the effect of parents' approval decreases for older adolescents, while the effect of peers' approval increases with age. No difference is found between girls and boys, while non-Swiss are more likely to smoke than Swiss students.
Conclusions
as literature suggests, results evidence the role parents play during early adolescence. Prevention programs targeting parent-child communication in early adolescence for preventing children's tobacco consumption are strongly supported.
doi:10.1371/journal.pone.0101275
PMCID: PMC4081496  PMID: 24991921
2.  Hospital Based Emergency Department Visits Attributed to Child Physical Abuse in United States: Predictors of In-Hospital Mortality 
PLoS ONE  2014;9(6):e100110.
Objectives
To describe nationally representative outcomes of physical abuse injuries in children necessitating Emergency Department (ED) visits in United States. The impact of various injuries on mortality is examined. We hypothesize that physical abuse resulting in intracranial injuries are associated with worse outcome.
Materials and Methods
We performed a retrospective analysis of the Nationwide Emergency Department Sample (NEDS), the largest all payer hospital based ED database, for the years 2008–2010. All ED visits and subsequent hospitalizations with a diagnosis of “Child physical abuse” (Battered baby or child syndrome) due to various injuries were identified using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes. In addition, we also examined the prevalence of sexual abuse in this cohort. A multivariable logistic regression model was used to examine the association between mortality and types of injuries after adjusting for a multitude of patient and hospital level factors.
Results
Of the 16897 ED visits that were attributed to child physical abuse, 5182 (30.7%) required hospitalization. Hospitalized children were younger than those released treated and released from the ED (1.9 years vs. 6.4 years). Male or female partner of the child’s parent/guardian accounted for >45% of perpetrators. Common injuries in hospitalized children include- any fractures (63.5%), intracranial injuries (32.3%) and crushing/internal injuries (9.1%). Death occurred in 246 patients (13 in ED and 233 following hospitalization). Amongst the 16897 ED visits, 1.3% also had sexual abuse. Multivariable analyses revealed each 1 year increase in age was associated with a lower odds of mortality (OR = 0.88, 95% CI = 0.81–0.96, p<0.0001). Females (OR = 2.39, 1.07–5.34, p = 0.03), those with intracranial injuries (OR = 65.24, 27.57–154.41, p<0.0001), or crushing/internal injury (OR = 4.98, 2.24–11.07, p<0.0001) had higher odds of mortality compared to their male counterparts.
Conclusions
In this large cohort of physically abused children, younger age, females and intracranial or crushing/internal injuries were independent predictors of mortality. Identification of high risk cohorts in the ED may enable strengthening of existing screening programs and optimization of outcomes.
doi:10.1371/journal.pone.0100110
PMCID: PMC4053408  PMID: 24919088
3.  Exposure to Beta-(1,3)-D-Glucan in House Dust at Age 7–10 Is Associated with Airway Hyperresponsiveness and Atopic Asthma by Age 11–14 
PLoS ONE  2014;9(6):e98878.
Background
Mould exposure has been linked to childhood asthma and bronchial hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta-glucan), a significant fungal cell wall constituent, in relation to asthma in adolescence.
Objective
To determine whether house dust-derived beta-glucan exposure at age 7–10 is associated with the development and persistence of atopic and non-atopic asthma, and bronchial hyper-responsiveness (BHR) by age 11–14.
Methods
Dust samples were collected from the 1995 Study of Asthma, Genes, and Environment (SAGE) birth cohort. This cohort was derived from Manitoba provincial healthcare administrative records of children high and low risk for asthma. Samples were collected from the homes of 422 children at age 7–10 and analyzed using beta-glucan and endotoxin-specific Limulus Amoebocyte Lysate assays. Asthma, atopy, and BHR status of each child were also assessed at ages 7–10 and 11–14.
Results
At age 7–10, beta-glucan dust levels in the home were associated with persistent atopic asthma at age 11–14 (OR 1.79 for each unit increase in levels, 95% CI 1.14–2.81), independent of endotoxin exposure, and Alternaria or Cladosporium sensitization. The likelihood of BHR almost doubled with unit increases in dust beta-glucan in asthmatic children. In children without asthma, exposure to high beta-glucan levels at age 7–10 also elevated risk for BHR in adolescence (OR 1.74, 95% CI 1.05–2.89). New-onset atopic asthma was twice more likely following high beta-glucan exposure in children without asthma but the association did not reach statistical significance. No associations were evident with concurrent asthma phenotype at age 7–10 or non-atopic asthma at age 11–14.
Conclusion
These findings implicate home beta-glucan exposure at school-age as a risk factor for persistent atopic asthma and new-onset BHR. The higher prevalence of BHR in urban adolescents may be propagated by this home exposure.
doi:10.1371/journal.pone.0098878
PMCID: PMC4048218  PMID: 24905346
4.  Guidelines for Improving Entry Into and Retention in Care and Antiretroviral Adherence for Persons With HIV: Evidence-Based Recommendations From an International Association of Physicians in AIDS Care Panel 
Annals of internal medicine  2012;156(11):817-294.
Description
After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). ART adherence is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV.
Methods
A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation.
Recommendations
Recommendations are provided for monitoring of entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.
doi:10.7326/0003-4819-156-11-201206050-00419
PMCID: PMC4044043  PMID: 22393036
5.  Macular optical coherence tomography findings following blunt ocular trauma 
This case report describes the optical coherence tomography (OCT) results of Berlin’s edema in a male subject following blunt ocular trauma from a soccer ball. A 27-year-old male presented with blurred vision in his left eye following blunt trauma. On admission, he underwent a complete eye examination and an OCT of the macula. Fundoscopy revealed commotio retinae, observed as an abnormal cream-colored discoloration of the fovea. The OCT showed outer photoreceptor segment disruption, retinal pigment epithelium inter-digitation, and intra-retinal edema of the outer nuclear layer. Following initial management, a repeat OCT after 3 months showed near complete resolution. OCT can be a useful adjunct for monitoring the progress of Berlin’s edema secondary to blunt ocular trauma because Berlin’s edema may present similarly clinically to other ocular trauma, but can affect different layers of the retina depending on the type of injury to the eye.
doi:10.2147/OPTH.S64082
PMCID: PMC4038424  PMID: 24899795
Berlin’s edema; commotio retinae; optical coherence tomography; OCT; ocular trauma
6.  Child maltreatment and adolescent mental health problems in a large birth cohort 
Child abuse & neglect  2013;37(5):292-302.
Objective
To examine whether notified child maltreatment is associated with adverse psychological outcomes in adolescence, and whether differing patterns of psychological outcome are seen depending on the type of maltreatment.
Methods
The participants were 7223 mother and child pairs enrolled in a population-based birth cohort study in Brisbane, Australia. Exposure to suspected child maltreatment was measured by linkage with state child protection agency data. The primary outcomes were the internalizing and externalizing scales of the Youth Self Report (YSR) at approximately 14 years of age.
Results
The YSR was completed by 5172 subjects (71.6%), with increased attrition of cases of notified maltreatment. After adjustment for potential confounders, notified maltreatment was significantly associated with both internalizing behavior and externalizing behavior at 14. When evaluated as non-exclusive categories of maltreatment, physical abuse, neglect, and emotional abuse were each significantly associated with both internalizing and externalizing behavior after adjustment. When evaluated using an expanded hierarchical scheme that included combinations of multi-type maltreatment, the following groups had significantly higher internalizing behavior after adjustment: emotional abuse (with or without neglect), and multi-type maltreatment including physical (but not sexual) abuse with neglect and/or emotional abuse. The following groups were associated with externalizing behavior after adjustment: emotional abuse (with or without neglect), and multi-type maltreatment including physical abuse (with neglect and/or emotional abuse), or sexual abuse (with neglect and/or emotional abuse, and/or physical abuse).
Conclusions
This study suggests that child neglect and emotional abuse have serious adverse effects on adolescent mental health and warrant the attention given to other forms of child maltreatment. Additionally, it confirms that young people who are notified for more than one type of maltreatment are at particular risk of adolescent mental health problems.
doi:10.1016/j.chiabu.2012.11.008
PMCID: PMC3918944  PMID: 23380430
7.  Adaptive Expression of MicroRNA-125a in Adipose Tissue in Response to Obesity in Mice and Men 
PLoS ONE  2014;9(3):e91375.
MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.
doi:10.1371/journal.pone.0091375
PMCID: PMC3967993  PMID: 24675842
8.  Effect of Crisis Plans on Admissions and Emergency Visits: A Randomized Controlled Trial 
PLoS ONE  2014;9(3):e91882.
Objective
To establish whether patients with a crisis plan had fewer voluntary or involuntary admissions, or fewer outpatient emergency visits, than patients without such a plan.
Design
Multicenter randomized controlled trial with two intervention conditions and one control condition.
Participants
Adult outpatients diagnosed with psychotic or bipolar disorder who had experienced at least one psychiatric crisis in the previous two years.
Intervention
Two types of advance statement were used: (1) a crisis plan formulated by the patient with the help of a patient advocate (Patient Advocate Crisis Plan: PACP); and (2) a crisis plan developed together with the clinician (Clinician-facilitated Crisis Plan: CCP).
Outcome
The percentages of patients admitted voluntarily or involuntarily (on an emergency basis or by court order), and the percentage who made outpatient emergency visits over an 18-month follow-up period.
Results
A total of 212 patients were included: 69 in the PACP condition, 70 in the CCP condition, and 73 in the control condition. No effects of the two interventions were found on the numbers of voluntary admissions, involuntary admissions and emergency visits. Regarding involuntary admissions, there was no significant effect on emergency admissions, which were 17% (12/69) in the PACP condition, 10% (7/70) in the CCP condition, and 19% (14/73) in the control condition. There was a significant effect on planned court-ordered admissions, with 16% (11/69) in the PACP condition, 10% (7/70) in the CCP condition, and 26% (19/73) in the control condition. Finally, the interventions had no effect on outpatient emergency visits, with 32% (22/69) in the PACP group, 31% (22/70) in the CCP group, and 34% (25/73) in the control group.
Conclusions
Crisis plans may be an effective intervention for reducing court-ordered admissions in patients with psychotic and bipolar disorders.
Trial registration
Current Controlled Trails NTR1166.
doi:10.1371/journal.pone.0091882
PMCID: PMC3960137  PMID: 24647274
9.  Replicating the Violence Risk Appraisal Guide: A Total Forensic Cohort Study 
PLoS ONE  2014;9(3):e91845.
Introduction
The performance of violence risk assessment instruments can be primarily investigated by analysing two psychometric properties: discrimination and calibration. Although many studies have examined the discrimination capacity of the Violence Risk Appraisal Guide (VRAG) and other actuarial risk assessment tools, few have evaluated how well calibrated these instruments are. The aim of the present investigation was to replicate the development study of the VRAG in Europe including measurements of discrimination and calibration.
Method
Using a prospective study design, we assessed a total cohort of violent offenders in the Zurich Canton of Switzerland using the VRAG prior to discharge from prisons, secure facilities, and outpatient clinics. Assessors adhered strictly to the assessment protocol set out in the instrument’s manual. After controlling for attrition, 206 offenders were followed in the community for a fixed period of 7 years. We used charges and convictions for subsequent violent offenses as the outcomes. Receiver operating characteristic analysis was conducted to measure discrimination, and Sanders’ decomposition of the Brier score as well as Bayesian credible intervals were calculated to measure calibration.
Results
The discrimination of the VRAG’s risk bins was modest (area under the curve = 0.72, 95% CI = 0.63–0.81, p<0.05). However, the calibration of the tool was poor, with Sanders’ calibration score suggesting an average assessment error of 21% in the probabilistic estimates associated with each bin. The Bayesian credible intervals revealed that in five out of nine risk bins the intervals did not contain the expected risk rates.
Discussion
Measurement of the calibration validity of risk assessment instruments needs to be improved, as has been done with respect to discrimination. Additional replication studies that focus on the calibration of actuarial risk assessment instruments are needed. Meanwhile, we recommend caution when using the VRAG probabilistic risk estimates in practice.
doi:10.1371/journal.pone.0091845
PMCID: PMC3954801  PMID: 24632561
11.  Intraventricular Hemorrhage and Multiple Intracranial Cysts Associated with Congenital Cytomegalovirus Infection 
Journal of Clinical Microbiology  2013;51(7):2466-2468.
Intraventricular hemorrhage with congenital cytomegalovirus (CMV) infection is rare and has been reported only in extremely premature infants or in association with thrombocytopenia. We report the first case of a full-term male infant with congenital CMV infection and intraventricular hemorrhage with a normal platelet count and coagulation profile. The infant also had a left subependymal cyst and bilateral occipital cysts without any other manifestations of CMV infection.
doi:10.1128/JCM.00842-13
PMCID: PMC3697656  PMID: 23678057
12.  Nutrigenomics of High Fat Diet Induced Obesity in Mice Suggests Relationships between Susceptibility to Fatty Liver Disease and the Proteasome 
PLoS ONE  2013;8(12):e82825.
Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD) feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J) and relative resistance (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.
doi:10.1371/journal.pone.0082825
PMCID: PMC3855786  PMID: 24324835
13.  Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal ligament fibroblasts: cigarette smoke induced alterations 
Tobacco Induced Diseases  2013;11(1):25.
Background
Cigarette smoking is the leading cause of preventable death and has been implicated in pathogenesis of pulmonary, oral and systemic diseases. Smoking during pregnancy is a risk factor for the developing fetus and may be a major cause of infant mortality. Moreover, the oral cavity, and all cells within are the first to be exposed to cigarette smoke and may be a possible source for the spread of toxins to other organs of the body. Fibroblasts in general are morphologically heterogeneous connective tissue cells with diverse functions. Apoptosis or programmed cell death is a crucial process during embryogenesis and for the maintenance of homeostasis throughout life. Deregulation of apoptosis has been implicated in abnormal lung development in the fetus and disease progression in adults. Caspases are proteases which belong to the family of cysteine aspartic acid proteases and are key components for downstream amplification of intracellular apoptotic signals. Of 14 known caspases, caspase-3 is the key executioner of apoptosis. In the present study we explored the hypothesis that cigarette smoke (CS) extract activates caspase-3 in two types of fibroblasts, both of which would be exposed directly to cigarette smoke, isolated fetal rat lung fibroblasts and adult rat periodontal ligament (PDL) fibroblasts.
Methods
Isolated fetal rat lung fibroblasts and adult PDLs were used. Cells were exposed to different concentrations of CS for 60 min. Caspase-3 activity and its inhibition by Z-VAD-fmk were measured by caspase-3 fluorometric assay. The effect of CSE on cellular viability was measured using the MTT formazan assay. Caspase-3 expression was detected by western blot analysis and cellular localization of caspase-3 was determined by immunofluorescence using fluorescence microscopy.
Results
It was observed in fetal rat lung fibroblast cells that CSE extract significantly (p<0.05) increased caspase-3 activity and decrease cell proliferation. However, no significant changes in activity or viability were observed in PDLs.
Conclusions
This indicates CS activates caspase-3 the key regulatory point in apoptosis in fetal rat lung fibroblast cells suggesting that smoking during pregnancy may alter the developmental program of fetal lung, jeopardizing the establishment of critical cellular mechanisms necessary to expedite pulmonary maturation at birth.of critical cellular mechanisms necessary to expedite pulmonary maturation at birth.
doi:10.1186/1617-9625-11-25
PMCID: PMC4029472  PMID: 24314135
Cigarette smoke extract; Fetal rat lung fibroblasts; Protease; Caspase-3; Lung development; Developmental toxicity; Periodontal ligament fibroblast; Periodontitis
14.  Associations between Parent-Adolescent Attachment Relationship Quality, Negative Life Events and Mental Health 
PLoS ONE  2013;8(11):e80812.
Purpose
The aim of this study was to examine the association of negative life events and parent-adolescent attachment relationship quality with mental health problems and to explore an interaction between the parent-adolescent attachment relationship and one or multiple negative life events on the mental health of adolescents.
Methods
A two-year longitudinal study was conducted among first-year secondary school students (N = 3181). The occurrence of life events and the quality of parent-adolescent attachment were assessed at baseline and mental health status at two-year follow-up by means of self-report questionnaires. Binary logistic regression analyses were conducted to assess associations between life events, parent-adolescent attachment and mental health problems. Relative Excess Risk due to Interaction techniques were used to determine the interaction effects on the additive scale.
Results
Life events were related to mental health status, as was parent-adolescent attachment. The combined effect of an unfavourable parent-adolescent attachment with life events on mental health was larger than the sum of the two individual effects. Among adolescents with one life event or multiple life events, an unfavourable parent-adolescent attachment increased the risk of mental health problems at follow-up compared to the group without life events.
Conclusion
Results supported an interaction effect between parent-adolescent attachment and negative life events on mental health. Especially adolescents with one or multiple life events and an unfavourable parent-adolescent attachment seems to be a vulnerable group for mental health problems. Implications for further research are discussed.
doi:10.1371/journal.pone.0080812
PMCID: PMC3843678  PMID: 24312244
15.  Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents 
PLoS ONE  2013;8(11):e81394.
Background
Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans.
Methods
Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort – matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves – pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale.
Results
Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected.
Conclusions
This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.
doi:10.1371/journal.pone.0081394
PMCID: PMC3838350  PMID: 24278432
16.  No Association between Antenatal Common Mental Disorders in Low-Obstetric Risk Women and Adverse Birth Outcomes in Their Offspring: Results from the CDS Study in Ghana and Côte D'Ivoire  
PLoS ONE  2013;8(11):e80711.
Background
Evidence linking common mental disorders (CMD) in pregnant women to adverse birth outcomes is inconsistent, and studies often failed to control for pregnancy complications. This study aimed to explore the association between antenatal depression and anxiety symptoms and birth outcomes in a low-obstetric risk sample of mother/child dyads in Ghana and Côte d’Ivoire.
Methods
In 2010-2011, a prospective cohort of 1030 women in their third trimester in Ghana and Côte d’Ivoire was enrolled. Depression and anxiety were assessed in the third trimester using the Patient Health Questionnaire depression module and the 7-item Generalized Anxiety Disorder scale. 719 mother/child dyads were included in the analysis. We constructed multivariate regression models to estimate the association between CMD and low birth weight (LBW), and preterm birth (PTB) to control for potential confounders.
Results
The prevalence of depression and anxiety symptoms were 28.9% and 14.2% respectively. The mean birth weight was 3172.1g (SD 440.6) and the prevalence of LBW was 1.7%. The mean gestational age was 39.6 weeks and the proportion of PTB was 4%. Multivariate linear regression revealed no significant association between maternal depression (B=52.2, 95% CI -18.2 122.6, p=0.15) or anxiety (B=17.1, 95% CI -74.6 108.7, p=0.72) and birth weight. Yet, low socio-economic status, female sex of the child, and younger maternal age were associated with lower birth weight. Multivariate logistic regression suggested no significant association between maternal depression (OR: 2.1, 95% CI 0.8 5.6, p=0.15) or anxiety (OR: 1.8, 95% CI 0.6 5.5, p=0.29) with PTB.
Conclusions
Our data suggests that depression and/or anxiety in the 3rd trimester of pregnancy are not independent predictors of adverse birth outcomes in low obstetric risk women. The role of pregnancy complications as confounders or effect modifiers in studies of maternal CMD and their impact on birth outcomes should be investigated.
doi:10.1371/journal.pone.0080711
PMCID: PMC3832471  PMID: 24260460
17.  Association of Aggression and Non-Suicidal Self Injury: A School-Based Sample of Adolescents 
PLoS ONE  2013;8(10):e78149.
Purpose
Non-suicidal self-injury (NSSI) in adolescent has drawn increasing attention because it is associated with subsequent depression, drug abuse, anxiety disorders, and suicide. In the present study, we aimed to estimate the prevalence of non-suicidal self-injury (NSSI) in a school-based sample of Chinese adolescents and to explore the association between aggression and NSSI.
Methods
This study was part of a nationwide study on aggression among adolescents in urban areas of China. A sample of 2907 school students including 1436 boys and 1471 girls were randomly selected in Guangdong Province, with their age ranging from 10 to 18 years old. NSSI, aggression, emotional management and other factors were measured by self-administrated questionnaire. Multinomial logistic regression was used to estimate the association between aggression and NSSI, after adjustment for participants’ emotional management, and other potential confounding variables.
Results
The one year self-reported prevalence of NSSI was 33.6%. Of them, 21.7% engaged in ‘minor NSSI’, 11.9% in ‘moderate/severe NSSI’. 96.9% of self-injuries engaged in one to five different types of NSSI in the past year. Hostility, verbal and indirect aggression was significantly associated with self-reported NSSI after adjusting for other potential factors both in ‘minor NSSI’ and ‘moderate/severe NSSI’. Hostility, verbal and indirect aggression was significantly associated with greater risk of ‘minor NSSI’ and ‘moderate/severe NSSI’ in those who had poor emotional management ability.
Conclusion
These findings highlight a high prevalence of NSSI and indicate the importance of hostility, verbal and indirect aggression as potentially risk factor for NSSI among Chinese adolescents.
doi:10.1371/journal.pone.0078149
PMCID: PMC3813494  PMID: 24205132
18.  Gender Differences in Neuropsychological Performance across Psychotic Disorders – a Multi-Centre Population Based Case-Control Study 
PLoS ONE  2013;8(10):e77318.
Background
Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.
Methods
Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.
Results
There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.
Conclusions
Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.
doi:10.1371/journal.pone.0077318
PMCID: PMC3810462  PMID: 24204806
19.  Screening Accuracy and Clinical Application of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) 
PLoS ONE  2013;8(8):e72602.
Background
The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a promising questionnaire for the early detection of psychosocial problems in toddlers. The screening accuracy and clinical application were evaluated.
Methods
In a community sample of 2-year-olds (N = 2060), screening accuracy of the BITSEA Problem scale was examined regarding a clinical CBCL1.5-5 Total Problem score. For the total population and subgroups by child’s gender and ethnicity Receiver Operating Characteristic (ROC) curves were calculated, and across a range of BITSEA Problem scores, sensitivity, specificity, likelihood ratio’s, diagnostic odds ratio and Youden’s index. Clinical application of the BITSEA was examined by evaluating the relation between the scale scores and the clinical decision of the child health professional.
Results
The area under the ROC curve (95% confidence interval) of the Problem scale was 0.97(0.95–0.98), there were no significant differences between subgroups. The association between clinical decision and BITSEA Problem score (B = 2.5) and Competence score (B = −0.7) was significant (p<0.05).
Conclusions
The results indicate that the BITSEA Problem scale has good discriminative power to differentiate children with and without psychosocial problems. Referred children had less favourable scores compared to children that were not referred. The BITSEA may be helpful in the early detection of psychosocial problems.
doi:10.1371/journal.pone.0072602
PMCID: PMC3758314  PMID: 24023626
20.  Identifying Probable Suicide Clusters in Wales Using National Mortality Data 
PLoS ONE  2013;8(8):e71713.
Background
Up to 2% of suicides in young people may occur in clusters i.e., close together in time and space. In early 2008 unprecedented attention was given by national and international news media to a suspected suicide cluster among young people living in Bridgend, Wales. This paper investigates the strength of statistical evidence for this apparent cluster, its size, and temporal and geographical limits.
Methods and findings
The analysis is based on official mortality statistics for Wales for 2000–2009 provided by the UK's Office for National Statistics (ONS). Temporo-spatial analysis was performed using Space Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and over, with a sub-group analysis focussing on cases aged 15–34 years. These analyses were conducted for deaths coded by ONS as: (i) suicide or of undetermined intent (probable suicides) and (ii) for a combination of suicide, undetermined, and accidental poisoning and hanging (possible suicides). The temporo-spatial analysis did not identify any clusters of suicide or undetermined intent deaths (probable suicides). However, analysis of all deaths by suicide, undetermined intent, accidental poisoning and accidental hanging (possible suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths amongst 15–34 year olds centred on the County Borough of Bridgend for the period 27th December 2007 to 19th February 2008. Less than 1% of possible suicides in younger people in Wales in the ten year period were identified as being cluster-related.
Conclusions
There was a possible suicide cluster in young people in Bridgend between December 2007 and February 2008. This cluster was smaller, shorter in duration, and predominantly later than the phenomenon that was reported in national and international print media. Further investigation of factors leading to the onset and termination of this series of deaths, in particular the role of the media, is required.
doi:10.1371/journal.pone.0071713
PMCID: PMC3756004  PMID: 24015189
21.  Service Use for Mental Health Problems in People with Delusional-Like Experiences: A Nationwide Population Based Survey 
PLoS ONE  2013;8(8):e71951.
Objective
Previous population-based studies have found that delusional-like experiences (DLEs) are prevalent in the community, and are associated with a wide range of mental health disorders. The aim of the study was to investigate mental health service use by people with DLEs.
Methods
Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007 of 8 841community residents aged between 16 and 85 years. The Composite International Diagnostic Interview (CIDI) was used to identify DLEs. Service utilization was assessed using a module that elicited information about hospital admissions, consultations with various health professionals, and prescription medication use. This study focussed on service use for mental health problems. We used logistic regression to examine the association, adjusting for potential confounding factors.
Results
Of 8 773 included participants, 8.4% (n = 776) positively endorsed one or more DLEs. With respect to consultations for mental health needs, individuals who endorsed DLEs were more likely to consult health professionals compared with those who did not endorse DLEs. Individuals with DLEs were also more likely to use prescription medicine. When we repeated the main analysis in a subgroup excluding any CIDI diagnosis of mental health disorders the results remained largely unchanged.
Conclusions
DLEs are common in the general population, and individuals with DLEs have an increased rate of accessing services for their mental health needs. Individuals endorsing both DLEs and increased help-seeking may identify a group of vulnerable people who have increased risk of developing psychotic illnesses later in life. This needs closer scrutiny in longitudinal prospective studies.
doi:10.1371/journal.pone.0071951
PMCID: PMC3749219  PMID: 23991012
22.  No Control Genes Required: Bayesian Analysis of qRT-PCR Data 
PLoS ONE  2013;8(8):e71448.
Background
Model-based analysis of data from quantitative reverse-transcription PCR (qRT-PCR) is potentially more powerful and versatile than traditional methods. Yet existing model-based approaches cannot properly deal with the higher sampling variances associated with low-abundant targets, nor do they provide a natural way to incorporate assumptions about the stability of control genes directly into the model-fitting process.
Results
In our method, raw qPCR data are represented as molecule counts, and described using generalized linear mixed models under Poisson-lognormal error. A Markov Chain Monte Carlo (MCMC) algorithm is used to sample from the joint posterior distribution over all model parameters, thereby estimating the effects of all experimental factors on the expression of every gene. The Poisson-based model allows for the correct specification of the mean-variance relationship of the PCR amplification process, and can also glean information from instances of no amplification (zero counts). Our method is very flexible with respect to control genes: any prior knowledge about the expected degree of their stability can be directly incorporated into the model. Yet the method provides sensible answers without such assumptions, or even in the complete absence of control genes. We also present a natural Bayesian analogue of the “classic” analysis, which uses standard data pre-processing steps (logarithmic transformation and multi-gene normalization) but estimates all gene expression changes jointly within a single model. The new methods are considerably more flexible and powerful than the standard delta-delta Ct analysis based on pairwise t-tests.
Conclusions
Our methodology expands the applicability of the relative-quantification analysis protocol all the way to the lowest-abundance targets, and provides a novel opportunity to analyze qRT-PCR data without making any assumptions concerning target stability. These procedures have been implemented as the MCMC.qpcr package in R.
doi:10.1371/journal.pone.0071448
PMCID: PMC3747227  PMID: 23977043
23.  Neighborhood Ethnic Diversity and Behavioral and Emotional Problems in 3 Year Olds: Results from the Generation R Study 
PLoS ONE  2013;8(8):e70070.
Background
Studies suggest that neighborhood ethnic diversity may be important when it comes to understanding ethnic inequalities in mental health. The primary aim of this study was to investigate whether neighborhood ethnic diversity moderated the association between the ethnic minority status and child behavioral and emotional problems.
Methods
We included 3076 preschoolers participating in the Generation R Study, a birth cohort study in Rotterdam, the Netherlands. At child age 3-years, parents completed the Child Behavior Checklist (CBCL/1,5-5). Individual-level data, assessed with questionnaires, was combined with neighborhood-level data. Multi-level logistic regression models predicted the Odds Ratios for the CBCL total problems score as a function of maternal ethnic background and neighborhood ethnic diversity, computed with the Racial Diversity Index and categorized into tertiles. Interaction on the additive scale was assessed using Relative Access Risk due to Interaction.
Results
Being from an ethnic minority was associated with child behavioral and emotional problems in unadjusted (OR 2.76, 95% CI 1.88–4.04) and adjusted models (OR 2.64, 95% CI 1.79–3.92). Residing in a high diversity neighborhood was associated with child behavioral and emotional problems in unadjusted (OR 2.03, 95% CI 1.13–3.64) but not in adjusted models (OR 0.89, 95% CI 0.51–1.57). When stratifying by the three levels of neighborhood ethnic diversity, ethnic inequalities in behavioral and emotional problems were greatest in low diversity neighborhoods (OR 5.24, 95%CI 2.47–11.14), smaller in high diversity neighborhoods (OR 3.15, 95% CI 1.66–5.99) and smallest in medium diversity neighborhoods (OR 1.59, 95% CI 0.90–2.82). Tests for interaction (when comparing medium to low diversity neighborhoods) trended towards negative on both the additive and multiplicative scale for the maternal-report (RERI: −3.22, 95% CI −0.70–0.59; Ratio of ORs: 0.30, 95% CI 0.12–0.76).
Conclusion
This study suggests that ethnic inequalities in child behavioral and emotional problems may be greatest in ethnically homogeneous neighborhoods.
doi:10.1371/journal.pone.0070070
PMCID: PMC3743872  PMID: 23967068
24.  Trends in Prevalence of Overweight and Obesity in Danish Infants, Children and Adolescents – Are We Still on a Plateau? 
PLoS ONE  2013;8(7):e69860.
Background
After the worldwide steep increase in child and adolescent overweight and obesity during the last decades, there is now evidence of a levelling off in the prevalence in many countries in the Western world.
Aim
To examine whether there still is a plateau in the prevalence of overweight and obesity in Danish children and adolescents, or whether the prevalence is decreasing or rising again.
Methods
The trends in the prevalence rates were based on three data sets providing comparable repeated estimates: 1) the Danish Health Visitors Child Health Database (DHVCHD) with measurements on infant and childhood height and weight from 2002 to 2011 (n up to 39,984), 2) the Danish National Birth Cohort (DNBC) with maternal reports of measured infant and childhood height and weight from 1998 to 2010 (n up to 56,826) and 3) the Danish part of the Health Behaviour in School-aged Children survey (HBSC) with self-reported information on adolescent height and weight from the years 2002 to 2010 (n = 16,557). Overweight and obesity were categorized according to WHO growth standards. Trends were assessed by repeated point estimates and linear regression analyses providing regression coefficients for changes in per cent per year with 95% confidence intervals (CI).
Results
The prevalence rates of overweight and obesity for infants, children and adolescents showed a mixed pattern of decline, stability and increase (ranging from -1.10 through 0.29 per cent per year with CI’s from -3.10 through 2.37). Overall, there were no consistent statistically significant trends upwards or downwards, although some significant downward trends in childhood and adolescence were observed.
Conclusion
This study, based on data from 1998 through 2011, showed that the prevalence rates of overweight and obesity among Danish infants, children and adolescents were largely still on a plateau with tendencies for a decline among children and adolescents.
doi:10.1371/journal.pone.0069860
PMCID: PMC3722196  PMID: 23894553
25.  My Child Redeems My Broken Dreams: On Parents Transferring Their Unfulfilled Ambitions onto Their Child 
PLoS ONE  2013;8(6):e65360.
From the early days of psychology, theorists have observed that parents sometimes transfer their own unfulfilled ambitions onto their child. We propose that parents are especially inclined to do so when they see their child as part of themselves, more so than as a separate individual. When parents see their child as part of themselves, their child’s achievements may easily come to function as a surrogate for parents’ own unfulfilled ambitions. In the present experiment, 73 parents (89% women, Mage = 43 years) were randomly assigned to reflect on either their own or others’ unfulfilled ambitions. Results showed that, when faced with their own unfulfilled ambitions, parents who see their child as part of themselves want their child to fulfill their unfulfilled ambitions. This study provides the first experimental evidence to suggest that parents may desire their child to redeem their broken dreams.
doi:10.1371/journal.pone.0065360
PMCID: PMC3686790  PMID: 23840325

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