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1.  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.
PMCID: PMC3967993  PMID: 24675842
2.  Effect of Crisis Plans on Admissions and Emergency Visits: A Randomized Controlled Trial 
PLoS ONE  2014;9(3):e91882.
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.
Multicenter randomized controlled trial with two intervention conditions and one control condition.
Adult outpatients diagnosed with psychotic or bipolar disorder who had experienced at least one psychiatric crisis in the previous two years.
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).
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.
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.
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.
PMCID: PMC3960137  PMID: 24647274
3.  Replicating the Violence Risk Appraisal Guide: A Total Forensic Cohort Study 
PLoS ONE  2014;9(3):e91845.
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.
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.
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.
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.
PMCID: PMC3954801  PMID: 24632561
5.  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.
PMCID: PMC3697656  PMID: 23678057
6.  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.
PMCID: PMC3855786  PMID: 24324835
7.  Associations between Parent-Adolescent Attachment Relationship Quality, Negative Life Events and Mental Health 
PLoS ONE  2013;8(11):e80812.
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.
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.
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.
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.
PMCID: PMC3843678  PMID: 24312244
8.  Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents 
PLoS ONE  2013;8(11):e81394.
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.
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.
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.
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.
PMCID: PMC3838350  PMID: 24278432
9.  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.
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.
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.
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.
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.
PMCID: PMC3832471  PMID: 24260460
10.  Association of Aggression and Non-Suicidal Self Injury: A School-Based Sample of Adolescents 
PLoS ONE  2013;8(10):e78149.
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.
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.
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.
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.
PMCID: PMC3813494  PMID: 24205132
11.  Gender Differences in Neuropsychological Performance across Psychotic Disorders – a Multi-Centre Population Based Case-Control Study 
PLoS ONE  2013;8(10):e77318.
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.
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.
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.
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.
PMCID: PMC3810462  PMID: 24204806
12.  Screening Accuracy and Clinical Application of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) 
PLoS ONE  2013;8(8):e72602.
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.
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.
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).
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.
PMCID: PMC3758314  PMID: 24023626
13.  Identifying Probable Suicide Clusters in Wales Using National Mortality Data 
PLoS ONE  2013;8(8):e71713.
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.
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.
PMCID: PMC3756004  PMID: 24015189
14.  Service Use for Mental Health Problems in People with Delusional-Like Experiences: A Nationwide Population Based Survey 
PLoS ONE  2013;8(8):e71951.
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.
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.
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.
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.
PMCID: PMC3749219  PMID: 23991012
15.  No Control Genes Required: Bayesian Analysis of qRT-PCR Data 
PLoS ONE  2013;8(8):e71448.
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.
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.
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.
PMCID: PMC3747227  PMID: 23977043
16.  Neighborhood Ethnic Diversity and Behavioral and Emotional Problems in 3 Year Olds: Results from the Generation R Study 
PLoS ONE  2013;8(8):e70070.
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.
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.
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).
This study suggests that ethnic inequalities in child behavioral and emotional problems may be greatest in ethnically homogeneous neighborhoods.
PMCID: PMC3743872  PMID: 23967068
17.  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.
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.
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.
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).
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.
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.
PMCID: PMC3722196  PMID: 23894553
18.  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.
PMCID: PMC3686790  PMID: 23840325
19.  A new exposure metric for traffic-related air pollution? An analysis of determinants of hopanes in settled indoor house dust 
Environmental Health  2013;12:48.
Exposure to traffic-related air pollution (TRAP) can adversely impact health but epidemiologic studies are limited in their abilities to assess long-term exposures and incorporate variability in indoor pollutant infiltration.
In order to examine settled house dust levels of hopanes, engine lubricating oil byproducts found in vehicle exhaust, as a novel TRAP exposure measure, dust samples were collected from 171 homes in five Canadian cities and analyzed by gas chromatography–mass spectrometry. To evaluate source contributions, the relative abundance of the highest concentration hopane monomer in house dust was compared to that in outdoor air. Geographic variables related to TRAP emissions and outdoor NO2 concentrations from city-specific TRAP land use regression (LUR) models were calculated at each georeferenced residence location and assessed as predictors of variability in dust hopanes.
Hopanes relative abundance in house dust and ambient air were significantly correlated (Pearson’s r=0.48, p<0.05), suggesting that dust hopanes likely result from traffic emissions. The proportion of variance in dust hopanes concentrations explained by LUR NO2 was less than 10% in Vancouver, Winnipeg and Toronto while the correlations in Edmonton and Windsor explained 20 to 40% of the variance. Modeling with household factors such as air conditioning and shoe removal along with geographic predictors related to TRAP generally increased the proportion of explained variability (10-80%) in measured indoor hopanes dust levels.
Hopanes can consistently be detected in house dust and may be a useful tracer of TRAP exposure if determinants of their spatiotemporal variability are well-characterized, and when home-specific factors are considered.
PMCID: PMC3711892  PMID: 23782977
Air pollution; Dust; Exposure assessment; Hopanes; Land use regression; Traffic
20.  Cyber Bullying Prevention: Intervention in Taiwan 
PLoS ONE  2013;8(5):e64031.
This study aimed to explore the effectiveness of the cyber bullying prevention WebQuest course implementation.
The study adopted the quasi-experimental design with two classes made up of a total of 61 junior high school students of seventh grade. The study subjects comprised of 30 students from the experimental group and 31 students from the control group. The experimental group received eight sessions (total 360 minutes) of the teaching intervention for four consecutive weeks, while the control group did not engage in any related courses. The self-compiled questionnaire for the student’s knowledge, attitudes, and intentions toward cyber bullying prevention was adopted. Data were analysed through generalized estimating equations to understand the immediate results on the student’s knowledge, attitudes, and intentions after the intervention. The results show that the WebQuest course immediately and effectively enhanced the knowledge of cyber bullying, reduced the intentions, and retained the effects after the learning. But it produced no significant impact on the attitude toward cyber bullying.
The intervention through this pilot study was effective and positive for cyber bulling prevention. It was with small number of students. Therefore, studies with large number of students and long experimental times, in different areas and countries are warranted.
PMCID: PMC3665829  PMID: 23724018
21.  Early Neurological Outcome of Young Infants Exposed to Selective Serotonin Reuptake Inhibitors during Pregnancy: Results from the Observational SMOK Study 
PLoS ONE  2013;8(5):e64654.
Use of selective serotonin reuptake inhibitors (SSRI) during pregnancy is common while the effect on the infant’s neurological outcome is unknown. Our objective was to determine the effects of prenatal SSRI-exposure on the infants’ neurological functioning, adjusted for maternal mental health.
A prospective observational study from May 2007 to April 2010. The study groups comprised 63 SSRI-exposed infants (SSRI group) and 44 non-exposed infants (non-SSRI group). Maternal depression and anxiety were measured using questionnaires. The main outcome measures during the first week after birth and at three to four months were the quality of the infants’ general movements (GMs) according to Prechtl and a detailed motor optimality score. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal GM quality in the SSRI and non-SSRI groups, and adjusted for maternal depression, anxiety, and other confounders. The study was registered under 53506435 in the ISRCTN.
All infants were born around term. During the first week, abnormal GMs occurred more frequently in the SSRI group than in the non-SSRI group (59% versus 33%) and the median MOS was lower (13 versus 18). The OR for abnormal GMs in the SSRI versus the non-SSRI group was 3·0 (95% CI, 1.3 to 6.9) and increased after adjustment for confounders. At three to four months, more SSRI-exposed infants had monotonous movements (48% versus 20%) with lower median MOSs (26 versus 28). The OR for monotonous movements was 3·5 (95% CI, 1.5 to 8.6) and increased after adjusting for confounders.
Prenatal exposure to SSRI had an adverse effect on early neurological functioning as reflected by GM quality, irrespective of maternal depression and anxiety, and other confounders. Physicians should take this into account in consultation with parents.
PMCID: PMC3665535  PMID: 23785389
22.  Economic Evaluation of Multisystemic Therapy for Young People at Risk for Continuing Criminal Activity in the UK 
PLoS ONE  2013;8(4):e61070.
To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England.
A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending.
108 adolescents, aged 11–17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI −£5,838 to £8,283).
The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research.
PMCID: PMC3632567  PMID: 23613786
23.  Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity 
Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.
The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.
Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.
This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
PMCID: PMC3655107  PMID: 23607879
Infants; Gut microbiota; Gut microbiome; Hygiene hypothesis; Microflora hypothesis; Pets; Siblings; Atopy; Allergic disease; Environmental exposures
24.  Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial 
Lancet neurology  2010;10(2):131-139.
The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury.
The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with, NCT00178711.
Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52).
This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury.
National Institute of Neurological Disorders and Stroke.
PMCID: PMC3628679  PMID: 21169065
25.  Meeting Report: Fungal ITS Workshop (October 2012) 
Standards in Genomic Sciences  2013;8(1):118-123.
This report summarizes a meeting held in Boulder, CO USA (19–20 October 2012) on fungal community analyses using ultra-high-throughput sequencing of the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA (rRNA) genes. The meeting was organized as a two-day workshop, with the primary goal of supporting collaboration among researchers for improving fungal ITS sequence resources and developing recommendations for standard ITS primers for the research community.
PMCID: PMC3739174  PMID: 23961317

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