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OBJECTIVES To analyze Australian national data to examine the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health-related hospital presentations among children and adolescents during the pandemic period with restrictions, and the period after the restrictions eased. METHODS We analyzed the monthly mental health-related inpatient admissions and emergency department (ED) attendances data from 6 large pediatric hospitals across Australia, using the Bayesian structural time series models. The COVID-19 restriction period was from March 2020 to December 2021 and the COVID-19 restriction-eased period from January to June 2022. RESULTS A total of 130 801 mental health-related hospital admissions (54 907) and ED attendances (75 894) were analyzed. During the COVID-19 restriction period, there was a significant increase in inpatient admissions related to deliberate self-harm behaviors (82%, 95% credible interval [CrI], 7%–160%) and ED attendances related to overall mental health disorders (15%, 95% CrI, 1.1%–30%) and eating disorders (76%, 95% CrI, 36%–115%). The increase was higher among females and those living in the least socioeconomically disadvantaged areas, suggesting a widening gap between mental health-related presentations by sex and socioeconomic status. After the restrictions eased, there were slight declines in mental health-related hospital presentations; however, the numbers remained higher than the pre–COVID-19 levels. CONCLUSIONS The increase in mental health-related hospital presentations during the COVID-19 period calls for additional support for pediatric mental health care, particularly for eating disorders and deliberate self-harm among female adolescents. It is important to monitor pediatric mental health service use as we enter “COVID-19 normal” period.

Sleep disorders are a common comorbid condition in children diagnosed with autism spectrum disorder ("autism"). However, the relationship between the clinical features of autism and sleep disorders remains unclear. A better understanding of the inherent autism-related characteristics linked to comorbid sleep disorders would improve comprehensive assessment and management. This study examined the relationship between sociodemographics, autism symptoms, sleep problems, cognitive status, behavioral attributes, and sensory profiles. Using data from 1268 participants who took part in the Australian Autism Biobank, sleep-related measurements using the Child Sleep Habits Questionnaire (CSHQ) were compared between autistic children aged 2 to 17 (N = 969), their siblings (N = 188), and unrelated children without an autism diagnosis (N = 111). The known relationship between sleep problems and autism was further explored by including scores from the Autism Diagnostic Observation Schedule-2, Mullen Scales of Early Learning, Vineland Adaptive Behavioral Scale-II and the Short Sensory Profile-2; which were included in analyses for autistic participants who had a completed CSHQ. Multiple regression models were used to identify clinical/behavioral variables associated with CSHQ subscales. The autism group had a significantly higher total CSHQ score than the sibling and comparison groups (p 0.001), indicating worse sleep quality. Within the autism group, lower adaptive behaviors (i.e., VABS-II) and sensory issues (i.e., SSP-2 subclass scores) were positively associated with the severity of sleep problems (i.e., the CSHQ subclass scores) (p 0.001). The significant functional impact of poor sleep on autistic children warrants an assessment of sleep as a critical part of a holistic approach to supporting autistic children and their families. LAY SUMMARY: Autistic children generally have co-occurring conditions. Sleep disorders impact approximately 50%-80% of autistic children. The impact on the quality of life for both the children and their families can be significant. This study compares sleep problems in autistic children and adolescents with their siblings and children without a diagnosis of autism, and investigates the relationship between specific autistic traits, daily life behaviors and sleep problems. The findings highlight the importance of a holistic assessment for autistic children and matching appropriate sleep intervention and supports where indicated.

Background: This study aims to determine whether visual attention bias is associated with the level of emotion dysregulation (ED) in children and which individual attributes may modify their relationship. Methods: A community-based sample of 50 children aged 3-8 years old was recruited. The level of ED in children was measured using the parental report measures: Child Behaviour Checklist and Temper Tantrum Scale. Visual attention bias measured as eye gaze fixation time in response to images showing various emotional expressions was measured using an eye-tracking task. Generalized linear models were used to evaluate whether visual attention bias was associated with ED when social function (measured with the Social Responsiveness Scale, gender, age, and attention problem (measured from the CBCL subscale), were adjusted. The modifying effect on visual attention bias was evaluated using the interaction analysis in the generalized linear model.Results: The level of visual attention bias, indicated by the proportion of eye gaze fixation time on areas of interest (AOIs) in images displaying unpleasant emotions (such as anger), was inversely associated with the level of externalising problem behaviours (p = .014). Additionally, the association of eye gaze fixation time for AOI displaying negative emotional cues with the level of externalising problem behaviours varied by age (p = .04), with younger children (aged

Investigating the change in the trend of ambulance service utilization for suicide in response to the COVID-19 pandemic can clarify the impact of the pandemic on acute health services. To determine whether the trends of the ambulance attendances related to self-injury and suicide changes in response to the COVID-19 pandemic. We extracted the data from the National Ambulance Surveillance System in Australia between March 2018 and March 2021 to examine the trajectory of the ambulance attendances related to self-injury and suicide. The results indicate that the number of ambulance attendances related to self-injury, suicidal ideation and suicidal attempt increased immediately during the first quarter since the outbreak and stayed higher over the at least 12 months. Notably, the post-outbreak surge in ambulance attendances associated with these mental health crises did not continue to escalate further. To sum up, the overall increase in ambulance attendances may reflect increased distress in the community, but also signify disruptions of other non-emergency health services. In contrast to recent evidence for the suicide rate being unchanged during the pandemic, our findings provide a different perspective on the impact of the pandemic on mental health services. This warrants a re-assessment of resources for mental health services in the post-COVID era.

The goal of the current study is to assess whether the scores of Brief Rating of Aggression by Children and Adolescents (BRACHA) at the emergency room (ER) can predict the aggressive incidents at pediatric psychiatric inpatient units. The study aims to identify predictors for two outcome measurements: 1) hazard rates for the first aggressive incident and 2) numbers of days between admission and the first aggressive incident, using the Cox regression model and Poisson regression model, respectively. The clinical records of a total of 5,610 adolescents admitted into the pediatric psychiatric inpatient units of Cincinnati Children's Hospital Medical Center were extracted for the analysis. The aggressive incident was defined as a score0 from any category of the Overt Aggression Scale (OAS) and the high-aggressive incident was defined as a score ≥ 2 from any category of the OAS. The results indicate that the BRACHA score was not associated with high-aggressive incidents (hazard ratio: 0.98, p = 0.7543). Similarly, the BRACHA scores was only associated with the number of days from admission to the first aggressive incident (Poisson regression coefficient: 0.24, p 0.0001) but not the number of days from admission to the first high-aggressive incident (Poisson regression coefficient: 0.03, p = 0.3994). Furthermore, the second peak of first aggressive incidents during the hospitalization highlights the importance of interventions at the end of the inpatient treatment course. To summarize, BRACHA scores based on initial assessments at the ER could correlate with first aggressive incidents, but not the first high-aggressive incidents.

BACKGROUND Research on problematic internet use has largely adhered to addiction paradigms, possibly impeding the identification of specific internet behaviors related to psychopathology. This study presents a novel approach to screening for specific problematic internet behaviors by using a new measure, the emergency department media use screener (EDMUS). OBJECTIVE The purpose of this study was to identify patterns of internet use in young people presenting with mental health concerns to the emergency department (ED), ascertain associations with their mental health, and evaluate whether the EDMUS can be used to predict subsequent ED presentations within 3 months. METHODS This cross-sectional retrospective study of Australian young people (N=149, aged 11-25 years; female: n=92, 61.7%) sought to use the EDMUS, a 24-item questionnaire, to identify problematic internet behaviors, including accessing or posting prosuicidal or proeating disorder content, cyberbullying, and inappropriate digital content. Data on each person’s mental health were extracted from electronic medical records to look for associations with EDMUS responses and ED re-presentation over 3 months. EDMUS items were grouped into clusters for analysis using chi-square tests, binary logistic regression, and path analyses. RESULTS Sharing suicidal digital content was the most common problematic internet use pattern identified by the EDMUS. However, this did not correlate with having a prior mental health diagnosis or predict readmission. Most participants had families with a concern for their internet use; however, this was less likely in participants with a diagnosis of personality disorder. Diagnoses of personality disorder or posttraumatic stress disorder were independent predictors of readmission (P=.003; P=.048). CONCLUSIONS Although a history of complex psychopathology increases the likelihood of subsequent ED presentations, its links to internet use–related behaviors are still unclear. The EDMUS has potential for identifying young people who are most vulnerable to problematic internet behaviors and offers the opportunity for early intervention and potential prevention of more entrenched difficulties.

AimsChildren on the autism spectrum are more likely to have sleep problems than non-autistic children. Sleep disturbance may exacerbate emotional and behavioral problems of children on the autism spectrum. A better understanding of the biological mechanisms underlying sleep disturbance provide clues to better management for this co-morbid condition in autism. The goal of the current study is to identify genetic variants associated with sleep disturbance and melatonin levels in autistic children.MethodsA total of 969 children on the autism spectrum were genotyped using the Global Screening Array v1 or Global Screening Array v2. Sleep problems were assessed using the Children's Sleep Habits Questionnaire (CSHQ). Melatonin levels were measured using the urine samples of 219 probands. The relationship between the melatonin level and CSHQ score was examined using the general linear model. The genetic variants associated with the CSHQ score and melatonin level as two separate quantitative traits were determined using genomewide association studies.ResultsThe data indicates that urine melatonin levels were positively associated with CSHQ scores, suggesting that autistic children with a poorer sleep qualiy could has higher melatonin level. Furthermore, genetic assocication studies suggest that genetic pathways involved in pro-inflammatory responses might be involved in sleep disturbance, while genetic pathways involved in catecholamine-secreting PC12 cells and Schwann cells could be associated with melatonin levels.ConclusionsTaken together, our findings indicate that sleep disturbance and melatonin metabolism could be attributable to distinct biological mechanisms in autistic children since they might not share genetic contributors.

Background Research on problematic internet use has largely adhered to addiction paradigms, possibly impeding the identification of specific internet behaviors related to psychopathology. This study presents a novel approach to screening for specific problematic internet behaviors by using a new measure, the emergency department media use screener (EDMUS). Objective The purpose of this study was to identify patterns of internet use in young people presenting with mental health concerns to the emergency department (ED), ascertain associations with their mental health, and evaluate whether the EDMUS can be used to predict subsequent ED presentations within 3 months. Methods This cross-sectional retrospective study of Australian young people (N=149, aged 11-25 years; female: n=92, 61.7%) sought to use the EDMUS, a 24-item questionnaire, to identify problematic internet behaviors, including accessing or posting prosuicidal or proeating disorder content, cyberbullying, and inappropriate digital content. Data on each person’s mental health were extracted from electronic medical records to look for associations with EDMUS responses and ED re-presentation over 3 months. EDMUS items were grouped into clusters for analysis using chi-square tests, binary logistic regression, and path analyses. Results Sharing suicidal digital content was the most common problematic internet use pattern identified by the EDMUS. However, this did not correlate with having a prior mental health diagnosis or predict readmission. Most participants had families with a concern for their internet use; however, this was less likely in participants with a diagnosis of personality disorder. Diagnoses of personality disorder or posttraumatic stress disorder were independent predictors of readmission (P=.003; P=.048). Conclusions Although a history of complex psychopathology increases the likelihood of subsequent ED presentations, its links to internet use–related behaviors are still unclear. The EDMUS has potential for identifying young people who are most vulnerable to problematic internet behaviors and offers the opportunity for early intervention and potential prevention of more entrenched difficulties.

Applications of machine learning (ML) in biomedical science are growing rapidly, spurred by interdisciplinary collaborations, aggregation of large datasets, accessibility of analytic routines, and availability of powerful computers. With this increased usage comes a responsibility for education, borne equally by data scientists plying their wares in medical research and biomedical scientists harnessing such methods to glean knowledge from data. This article provides a critical review of ML, covering common ML methods and historical trends of their use in psychiatry, and identifying areas of opportunity for future applications of ML in biological psychiatry. We also establish the ML in Psychiatry (MLPsych) Consortium, enumerate its objectives, and provide a set of standards (Guidelines for REporting ML Investigations in Neuropsychiatry [GREMLIN]) for designing and reporting studies that use ML. This review serves as a cautiously optimistic primer on ML for those on the precipice as they prepare to dive into the field, either as dedicated methodological practitioners or, at the very least, well-informed consumers.

Background: The COVID-19 pandemic and its concomitant impacts have been unevenly shared across society, this is particularly true for children with neurodevelopmental disorders (NDD), who often rely on a network of services and social connections for their well-being. Children with NDD during the COVID-19 pandemic have had worrying trends regarding their worsening well-being and poorer parental mental health. This study’s aim was to test whether these two factors were associated in a survey of Australian parents.Methods: This cross-sectional study of Australian parents of children with neurodevelopmental disorders (n = 304, ages 2 – 17, 63.8% male) sought to test the association between parental distress (as captured by the Kessler-6 distress scale) and two child outcomes, worsening NDD symptoms and worsening health behaviours (i.e., sleep, diet, exercise, and media use).Results: Parent distress was significantly associated with a worsening of symptoms of NDD and associated mental health comorbidities, and poorer child well-being. These results were significant even when including other variables of interest such as the families’ sociodemographic characteristics, indicating parental distress is a key factor for the well-being of children and parents.Conclusions: Overall, this study found relatively high levels of parental psychological distress, anxiety and poor well-being and demonstrated that parental psychological distress was significantly associated with parent-reported worsening of child diagnostic symptoms as well as poorer child well-being in relation to sleep, diet, exercise, and use of electronics. Together these findings suggest that deteriorating parental mental health (distress) due to COVID-19 is associated with adverse child mental health symptoms and well-being, as indexed by the behaviours described above.

Background: Individuals with autism spectrum disorder (ASD) have heterogeneous comorbid conditions. This study examined whether comorbid conditions in ASD are associated with polygenic risk scores (PRS) of ASD or PRS of comorbid conditions in non-ASD specific populations. Genome-wide single nucleotide polymorphism (SNP) data were obtained from 1,386 patients with ASD from the Autism Genetic Resource Exchange (AGRE) study. After excluding individuals with missing clinical information concerning comorbid conditions, a total of 707 patients were included in the study. Methods: A total of 18 subgroups of comorbid conditions (’topics’) were identified using a machine learning algorithm, topic modeling. PRS for ASD were computed using a genome-wide association meta-analysis of 18,381 cases and 27,969 controls. Results: From these 18 topics, Topic 6 (over-represented by allergies) ( p = 1.72x10 − 3 ) and Topic 17 (over-represented by sensory processing issues such as low pain tolerance) ( p = .037) were associated with PRS of ASD. For associated topics, we further assessed their associations with PRS of their corresponding comorbid conditions based on non-ASD specific populations. However, these two topics were not associated with the PRS of allergies and chronic pain disorder, respectively. Limitations: Characteristics of the present AGRE sample and those samples used in the original GWAS for ASD, allergies, and chronic pain disorder, may differ due to significant clinical heterogeneity that exists in the ASD population. Additionally, the AGRE sample may be underpowered and therefore insensitive to weak PRS associations due to low relatively small sample size. Conclusions: Findings imply that susceptibility genes of ASD may contribute more to the occurrence of allergies and sensory processing issues in individuals with ASD, compared with the susceptibility genes for their corresponding phenotypes. Since these comorbid conditions (i.e., allergies and pain sensation issues) cannot be attributable to the corresponding comorbidity-specific biological factors in non-ASD individuals, clinical management for these comorbid conditions may still depend on treatments for core symptoms of ASD.

Background Perfluoroalkyl substances (PFASs) are widespread, bioaccumulating, and persistent and show placental transfer. Emerging research indicates associations between prenatal exposure and low birth weight. The aim of this study was to assess the associations between first trimester exposure to PFASs and birth weight (BW) in the Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy (SELMA) study and examine whether associations differ between girls and boys. Methods Eight PFASs were analyzed in maternal serum (median: 10 weeks of pregnancy). Associations between prenatal PFAS exposure and birth outcomes with BW, BW for gestational age, and birth small for gestational age (SGA) were assessed in 1533 infants, adjusted for potential confounders and stratified by sex. Results Increased maternal perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with lower BW, lower BW for gestational age, and SGA birth. Associations were significant only in girls, where prenatal exposure in the upper quartile was associated with a 93–142-g lower BW when compared with that of the lowest quartile exposure. The associations were not mediated by effects on gestational age. Conclusions We found associations between prenatal exposure for five different PFASs and birth weight, with more pronounced associations in girls than in boys.

Psychiatric symptoms are seen in some COVID-19 patients, as direct or indirect sequelae, but it is unclear whether SARS-CoV-2 infection interacts with underlying neuronal or psychiatric susceptibilities. Such interactions might arise from COVID-19 immune responses, from infection of neurons themselves or may reflect social-psychological causes. To clarify this we sought the key gene expression pathways altered in COVID-19 also affected in bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia, since this may identify pathways of interaction that could be treatment targets. We performed large scale comparisons of whole transcriptome data and immune factor transcript data in peripheral blood mononuclear cells (PBMC) from COVID-19 patients and patients with psychiatric disorders. We also analysed genome-wide association study (GWAS) data for symptomatic COVID-19 patients, comparing GWAS and whole-genome sequence data from patients with bipolar disorder, PTSD and schizophrenia patients. These studies revealed altered signalling and ontology pathways shared by COVID-19 patients and the three psychiatric disorders. Finally, co-expression and network analyses identified gene clusters common to the conditions. COVID-19 patients had peripheral blood immune system profiles that overlapped with those of patients with psychiatric conditions. From the pathways identified, PTSD profiles were the most highly correlated with COVID-19, perhaps consistent with stress-immune system interactions seen in PTSD. We also revealed common inflammatory pathways that may exacerbate psychiatric disorders, which may support the usage of anti-inflammatory medications in these patients. It also highlights the potential clinical application of multi-level dataset studies in difficult-to-treat psychiatric disorders in this COVID-19 pandemic.

Marine debris and floating marine debris issues have recently become a matter of great concern. The present study selected Kenting National Park and Northeast Cape and Yilan Coast National Scenic Area as the survey areas, where most of the popular scuba diving spots in Taiwan are located, to identify the volume, types, and sources of marine litter. The findings could be regarded as the foundation for future study and the suggestions for managerial strategies. The visual and line transect methods were used to conduct fourteen investigations of marine litter in four scuba diving spots from June 2020 to November 2020. Descriptive analysis and the chi-square test were used to analyze the volume, types, and sources of marine litter, as well as the different distributions under diverse locations, terrains, season, and tides. The results indicate that 2841 pieces of marine litter are identified, including 1786 (63%) plastic containers, 312 (11%) plastic bags, 254 (9%) disposable tableware for take-out beverages, 285 (10%) other materials, 72 (2%) cigarette butts, and 30 (1%) fishery and recreational fishing pieces. Different seasons, locations, and tides cause a significantly different marine litter distribution among these areas. The findings are expected to promote source reduction, develop shore and underwater cleaning proposals, and enhance marine protection education.

BACKGROUND Accurate prediction of the disease severity of patients with COVID-19 would greatly improve care delivery and resource allocation and thereby reduce mortality risks, especially in less developed countries. Many patient-related factors, such as pre-existing comorbidities, affect disease severity and can be used to aid this prediction. OBJECTIVE Because rapid automated profiling of peripheral blood samples is widely available, we aimed to investigate how data from the peripheral blood of patients with COVID-19 can be used to predict clinical outcomes. METHODS We investigated clinical data sets of patients with COVID-19 with known outcomes by combining statistical comparison and correlation methods with machine learning algorithms; the latter included decision tree, random forest, variants of gradient boosting machine, support vector machine, k-nearest neighbor, and deep learning methods. RESULTS Our work revealed that several clinical parameters that are measurable in blood samples are factors that can discriminate between healthy people and COVID-19–positive patients, and we showed the value of these parameters in predicting later severity of COVID-19 symptoms. We developed a number of analytical methods that showed accuracy and precision scores >90% for disease severity prediction. CONCLUSIONS We developed methodologies to analyze routine patient clinical data that enable more accurate prediction of COVID-19 patient outcomes. With this approach, data from standard hospital laboratory analyses of patient blood could be used to identify patients with COVID-19 who are at high risk of mortality, thus enabling optimization of hospital facilities for COVID-19 treatment.

BackgroundClinical heterogeneity in autism spectrum disorder (ASD) can complicate diagnostics and treatments. The identification of biomarkers may hold the key to the classification of ASD subgroups. Accumulating evidence suggests that genetic or genomic markers may facilitate the clustering of patients with ASD. The goal of the current study is to use machine learning algorithms to analyze microarray data to identify clusters with relatively homogeneous clinical features, such as language function.MethodsThe whole-genome gene expression microarray data were used to predict communication quotient (SCQ) scores against all probes to select differential expression regions (DERs). Gene set enrichment analysis was performed to identify hub pathways that play a role in the severity of social communication deficits inherent to ASD. We then used two machine learning methods, random forest classification (RF) combined with partition around medoids (PAM) and support vector machine (SVM), to identify two clusters using DERs. Finally, we evaluated how accurately the clusters predicted language impairment.ResultsA total of 191 DERs were identified. Cholesterol biosynthesis and metabolisms pathways appear to act as hubs that connect other trait-associated pathways to influence the severity of social communication deficits inherent to ASD. Both RF and SVM algorithms can yield a classification accuracy level greater than 90% when all 191 DERs were analyzed. LimitationsThe primary limitation of the current study is the small sample size. Nevertheless, some machine learning algorithm, such as SVM, can handle a small sample with a large number of features. Additionally, model overfitting may arise due to a lack of another independent sample for validation. Furthermore, unknown confounders may cause spurious associations between the phenotype and genomic markers. ConclusionsThe ASD subtypes defined by the presence of language impairment, a strong indicator for prognosis, can be predicted by transcriptomic profiles associated with social communication deficits and cholesterol biosynthesis and metabolism. Our proof-of-concept study suggests that both RF and SVM are acceptable options for machine learning algorithms to identify AD subgroups characterized by clinical homogeneity related to prognosis.

BACKGROUND The COVID-19 pandemic has overwhelmed health care systems around the world. Emerging evidence has suggested that substantially few patients seek help for suicidality at clinical settings during the COVID-19 pandemic, which has elicited concerns of an imminent mental health crisis as the course of the pandemic continues to unfold. Clarifying the relationship between the public’s attention to knowledge about suicide and the public’s attention to knowledge about the COVID-19 pandemic may provide insight into developing prevention strategies for a putative surge of suicide in relation to the impact of the COVID-19 pandemic. OBJECTIVE The goal of this retrospective, longitudinal time-series study is to understand the relationship between temporal trends of interest for the search term “suicide” and those of COVID-19–related terms, such as “social distancing,” “school closure,” and “lockdown.” METHODS We used the Google Trends platform to collect data on daily interest levels for search terms related to suicide, several other mental health-related issues, and COVID-19 over the period between February 14, 2020 and May 13, 2020. A correlational analysis was performed to determine the association between the search term ‘‘suicide’’ and COVID-19–related search terms in 16 countries. The Mann-Kendall test was used to examine significant differences between interest levels for the search term “suicide” before and after school closure. RESULTS We found that interest levels for the search term “suicide” statistically significantly inversely correlated with interest levels for the search terms “COVID-19” or “coronavirus” in nearly all countries between February 14, 2020 and May 13, 2020. Additionally, search interest for the term ‘‘suicide’’ significantly and negatively correlated with that of many COVID-19–related search terms, and search interest varied between countries. The Mann-Kendall test was used to examine significant differences between search interest levels for the term “suicide” before and after school closure. The Netherlands (P=.19), New Zealand (P=.003), the United Kingdom (P=.006), and the United States (P=.049) showed significant negative trends in interest levels for suicide in the 2-week period preceding school closures. In contrast, interest levels for suicide had a significant positive trend in Canada (PP=.002) after school closures. CONCLUSIONS The public’s attention to suicide might inversely correlate with the public’s attention to COVID-19–related issues. Additionally, several anticontagion policies, such as school closure, might have led to a turning point for mental health crises, because the attention to suicidality increased after restrictions were implemented. Our results suggest that an increased risk of suicidal ideation may ensue due to the ongoing anticontagion policies. Timely intervention strategies for suicides should therefore be an integral part of efforts to flatten the epidemic curve.

Additional file 1: Table S1. Estimated fecundability ratio (FR) for time-to-pregnancy (TTP) and odds ratio (OR) for infertility prior to stratification. Data are presented as FR (95% CI) or OR (95% CI). Supp Figure S1. Flowchart of recruitment process and analyses in the SELMA study. Abbreviations: COC – combined oral contraceptives; FR – fecundability ratio; OR – odds ratio; POPs – persistent organic pollutants; TTP – time-to-pregnancy; WQS – weighted quantile sum. Supp Figure S2. Sensitivity analyses with censoring at 10 months. Dot shows fecundability ratio (FR) with 95% confidence interval error bars of chemicals as continuous (log) and quartiles (Q1 as reference). FR > 1 denotes higher fecundability and shorter TTP while FR 1 denotes higher fecundability and shorter TTP while FR

Purpose Enterprises must select the best optimal endorser-product fit in order to maximize the limited budget available for endorsements. Previous studies have determined that the influence of athlete endorsers is greater than is that of celebrity endorsers on consumer attitudes toward sport products. However, different endorsers may possess different levels of influence on products. The paper aims to discuss these issues. Design/methodology/approach This study developed two field experiments to investigate the influence of endorser-product fits on consumer purchase intentions. Participants in Study 1 were 295 individuals (220 male consumers, 75 female consumers, M age=32 yr) in the two Baseball Stadiums in Taiwan. Participants in Study 2 were 317 EMBA students (204 men, 113 women, M age=34 yr) at a certain university in Taiwan. Findings The results determined no significant moderating effect of celebrity endorser-product fit and purchase intention, whereas athlete endorser-product fit enhanced consumers’ purchase intentions in low product involvement scenarios. In high product involvement scenarios, a moderating relationship between endorser-product fit and purchase intentions was observed. These findings can provide a reference regarding endorsers and product patterns for enterprises to maximize the value of endorsers. Originality/value Using the multiple endorser-product patterns, this study provides useful findings in terms of the perceived value of endorser-product and purchase intention. The results of this study can help enterprises to choose the most suitable endorser when they are subject to budget constraints. Detailed descriptions of the expected results and discussion are reported in the text.

The aim of this research is to examine the relation between school attachment and school achievement and foster care placement. A cross-sectional study was carried out with data from 20 340 pupils in Sweden, aged 10, 13 and 16 years, 252 of the children were placed in foster care. Data on children's health, school attachment and school achievement were obtained from the Pupil Health Database. The results show that school achievement was significantly poorer for children in foster care than for other children, but only when they had low school attachment. When they had high school attachment, there was no difference in school achievement between the groups. Therefore, the results of this study suggests that school attachment could modify the relation between foster care placement and school achievement. The interaction effect was statistically significant after adjusting for age and sex. By promoting school attachment for children in foster care through creating supportive relations and a friendly school environment, the school achievement can be improved.

DNA methylation (DNAm) profiles in central airway epithelial cells (AECs) may play a key role in pathological processes in asthma. The goal of the current study is to compare the diagnostic performance of DNAm markers across three tissues: AECs, nasal epithelial cells (NECs), and peripheral blood mononuclear cells (PBMCs). Additionally, we focused on the results using the machine learning algorithm in the context of multi-locus effects to evaluate the diagnostic performance of the optimal subset of CpG sites. We obtained 74 subjects with asthma and 41 controls from AECs, 15 subjects with asthma and 14 controls from NECs, 697 subjects with asthma and 97 controls from PBMCs. Epigenome-wide DNA methylation levels in AECs, NECs and PBMCs were measured using the Infinium Human Methylation 450 K BeadChip. Overlap analysis across the three different sample sources at the locus and pathway levels were studied to investigate shared or unique pathophysiological processes of asthma across tissues. Using the top 100 asthma-associated methylation markers as classifiers from each dataset, we found that both AEC- and NEC-based DNAm signatures exerted a lower classification error than the PBMC-based DNAm markers (p-value = 0.0002). The area-under-the-curve (AUC) analysis based on out-of-bag errors using the random forest classification algorithm revealed that PBMC-, NEC-, and AEC-based methylation data yielded 31 loci (AUC: 0.87), 8 loci (AUC: 0.99), and 4 loci (AUC: 0.97) from each optimal subset of tissue-specific markers, respectively. We also discovered the locus-locus interaction of DNAm levels of the CDH6 gene and RAPGEF3 gene might interact with each other to jointly predict the risk of asthma – which suggests the pivotal role of cell-cell junction in the pathological changes of asthma. Both AECs and NECs might provide better diagnostic accuracy and efficacy levels than PBMCs. Further research is warranted to evaluate how these tissue-specific DNAm markers classify and predict asthma risk.

Past studies have suggested that conditions experienced by women during pregnancy (e.g. obesity and gestational diabetes mellitus (GDM)) may be associated with having a child with autism spectrum disorder (ASD). Our objective was to compare mothers who had a child diagnosed with ASD to mothers of children with a non-ASD developmental disorder (DD) or without any reported DD (controls). To accomplish the objective we collected medical record data from patients who resided in the Cincinnati Children's Hospital Medical Center's (CCHMC) primary catchment area and linked those data to data from birth certificates (to identify risk factors). Two comparison groups were analyzed; one with DD; and the other, controls without a reported ASD or DD. Descriptive statistics and regression analyses evaluated differences. Differences were greater comparing mothers of ASD to controls than comparing ASD to DD. Maternal obesity and GDM were associated with a statistically significant approximately 1.5-fold increased odds of having a child with an ASD. For mothers with both GDM and obesity, the association was twofold for having a child with ASD compared with controls. Maternal obesity and GDM might be associated with an increased risk of ASD in the offspring; however, no difference in risk of ASD according to BMI and GDM was seen when comparing to DD. Autism Res 2016, 9: 829-837,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Bisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, low APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and low APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.

Social information processing theory hypothesizes that aggressive children pay more attention to cues of hostility and threat in others’ behavior, consequently leading to over-interpretation of others’ behavior as hostile. While there is abundant evidence of aggressive children demonstrating hostile attribution biases, less well documented is whether such biases stem from over-attendance and hypersensitivity to hostile cues in social situations. Over-attendance to hostile cues would be typified by deviations at any stage of the multi-stage process of social information processing models. While deviations at later stages in social information processing models are associated with aggressive behavior in children, the initial step of encoding has historically been difficult to empirically measure, being a low level automatic process unsuitable for self-report. We employed eye-tracking methodologies to better understand the visual encoding of such social information. Eye movements of ten 13–18 year-old children referred from clinical and non-clinical populations were recorded in real time while the children viewed scenarios varying between hostile, non-hostile and ambiguous social provocation. In addition, the children completed a brief measure of risk of aggression. Aggressive children did attend more to the social scenarios with hostile cues, in particular attending longest to those hostile scenarios where the actor in the scenario had a congruent emotional response. These findings corroborate social information processing theory and the traditional bottom-up processing hypotheses that aggressive behavior relates to increased attention to hostile cues.

Little is known regarding the time trend of mass shootings and associated risk factors. In the current study, we intended to explore the time trend and relevant risk factors for mass shootings in the U.S. We attempted to identify factors associated with incidence rates of mass shootings at the population level. We evaluated if state-level gun ownership rate, serious mental illness rate, poverty percentage, and gun law permissiveness could predict the state-level mass shooting rate, using the Bayesian zero-inflated Poisson regression model. We also tested if the nationwide incidence rate of mass shootings increased over the past three decades using the non-homogenous Poisson regression model. We further examined if the frequency of online media coverage and online search interest levels correlated with the interval between two consecutive incidents. The results suggest an increasing trend of mass shooting incidences over time (p < 0.001). However, none of the state-level variables could predict the mass shooting rate. Interestingly, we have found inverse correlations between the interval between consecutive shootings and the frequency of on-line related reports as well as on-line search interests, respectively (p < 0.001). Therefore, our findings suggest that online media might correlate with the increasing incidence rate of mass shootings. Future research is warranted to continue monitoring if the incidence rates of mass shootings change with any population-level factors in order to inform us of possible prevention strategies.

Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. Development of 3-dimensionsal melanospheres that in vitro partially recapitulate non-invasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase (pFAK) and increased melanoma cell responsiveness to transforming growth factor-beta (TGF-β), both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence.

The mechanisms underlying aggression in adolescents with bipolar disorder have been poorly understood. The present study has investigated the associations among TNF gene expressions, functional brain activations under the frustrative non-reward task, and aggression in adolescents with bipolar disorder. Baseline gene expressions and aggressive tendencies were measured with the RNA-sequencing and Brief Rating of Aggression by Children and Adolescents (BRACHA), respectively. Our results show that activity levels of left subgenual anterior cingulate gyrus (ACG) right amygdala, left Brodmann area 10 (orbitofrontal cortex), and right thalamus were inversely correlated with BRACHA scores and were activated with frustrative non-reward during the affective Posner Task. In addition, eleven TNF related gene expressions were significantly correlated with activation of amygdala or ACG during the affective Posner task. Three TNF gene expressions were inversely correlated with BRACHA score while one TNF gene (TNFAIP3) expression was positively correlated with BRACHA score. Therefore, TNF-related inflammatory cytokine genes may play a role in neural activity associated with frustrative non-reward and aggressive behaviors in pediatric bipolar disorder.

Persistent organic pollutants, pre-pregnancy use of combined oral contraceptive and time-to-pregnancy in SELMA cohort

Carbon coils of micrometer to nanometer wire diameter were grown bi-directionally by catalyst-assisted chemical vapor deposition. Electron microscope images showed the highly disordered structure of the carbon coils. Chemical compositions of the coils were identified with elemental analysis, atmospheric pressure-laser desorption ionization-Fourier-transform ion cyclotron resonance-mass spectroscopy and secondary ion mass spectrometric characterizations, and attenuated total reflection-infrared spectroscopic examination. Micro-Raman scattering spectroscopy and electron energy loss spectroscopy were also used to study the vibrational and electronic properties of the helical structure. The electric transport in a single carbon coil was measured from ambient temperature to 64 mK. The temperature-dependent resistance was analyzed with the Efros-Shklovskii variable range hopping model, indicating three-dimensional electron hopping conduction in the disordered helical wires. The analysis also provides a basic understanding of the electron transport with an electron hopping length of ∼5 nm inside the disordered carbon coils.

Historically, data for genetic studies are collected at one time point. However, for diseases with late onset or with complex phenotypes, such as Alzheimer disease (AD), restricting diagnosis to a single ascertainment contact may not be sufficient. Affection status may change over time and some initial diagnoses may be inconclusive. Follow-up provides the opportunity to resolve these complications. However, to date, previous studies have not formally demonstrated that longitudinally re-contacting families is practical or productive. To update data initially collected for linkage analysis of late-onset Alzheimer disease (LOAD), we successfully re-contacted 63 of 81 (78%) multiplex families (two to 17 years after ascertainment). Clinical status changed for 73 of the 230 (32%) non-affected participants. Additionally, expanded family history identified 20 additional affected individuals to supplement the data set. Furthermore, fostering ongoing relationships with participating families helped recruit 101 affected participants into an autopsy and tissue donation program. Despite similar presentations, discordance between clinical diagnosis and neuropathologic diagnosis was observed in 28% of those with tissue diagnoses. Most of the families were successfully re-contacted, and significant refinement and supplementation of the data was achieved. We concluded that serial contact with longitudinal evaluation of families has significant implications for genetic analyses.

Since Emil Kraepelin proposed in 1919 that dementia praecox (schizophrenia) be differentiated from manic depression (bipolar disorder), the concept of nosological dichotomy has greatly influenced the diagnosis, treatment, and research of pathogenesis of these 2 disorders. However, this concept has recently been challenged by increasing evidence showing biological overlap between schizophrenia and bipolar disorder. This article reviews some of the previous evidence for phenomenological and molecular overlaps between these 2 disorders. We then discuss approaches for examining shared etiological mechanisms with a concentration on genetic factors. We have put a particular emphasis on incorporating the concept of endophenotypes in research of shared genetic liability for these 2 disorders.

Past studies have suggested that conditions experienced by women during pregnancy (e.g. obesity and gestational diabetes mellitus (GDM)) may be associated with having a child with autism spectrum disorder (ASD). Our objective was to compare mothers who had a child diagnosed with ASD to mothers of children with a non-ASD developmental disorder (DD) or without any reported DD (controls). To accomplish the objective we collected medical record data from patients who resided in the Cincinnati Children's Hospital Medical Center's (CCHMC) primary catchment area and linked those data to data from birth certificates (to identify risk factors). Two comparison groups were analyzed; one with DD; and the other, controls without a reported ASD or DD. Descriptive statistics and regression analyses evaluated differences. Differences were greater comparing mothers of ASD to controls than comparing ASD to DD. Maternal obesity and GDM were associated with a statistically significant approximately 1.5-fold increased odds of having a child with an ASD. For mothers with both GDM and obesity, the association was twofold for having a child with ASD compared with controls. Maternal obesity and GDM might be associated with an increased risk of ASD in the offspring; however, no difference in risk of ASD according to BMI and GDM was seen when comparing to DD. Autism Res 2016, 9: 829-837,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Patients with chronic depression may suffer from global cognitive defects. Here, we present a case with repetitive mild traumatic brain injuries (mTBI) that aggravated her depressive symptoms and exhibited atypical cognitive impairments. Her depressive symptoms had been resistant to a combination of SNRI and antipsychotics. The single-photon emission computed tomography scan showed asymmetric perfusion at medial temporal lobes - which has been found to be associated with somatic delusions in some other patients. Her cognitive impairment profile was also consistent with difficulty in inhibition and visual processing, as noted in medial temporal lobe dysfunction, but not commonly seen in chronic depression. After her depression was improved with antipsychotic medications, her specific cognitive impairments persisted. To conclude, repetitive mTBI might cause selective or atypical cognitive impairments that impact treatment responses in patients with depressive disorders.

We previously reported a linkage region on chromosome 10q for age-at-onset (AAO) of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2 (hereafter referred to as GSTO1h) are responsible for the linkage evidence, we identified 39 families in AD that lead to our previous linkage and association findings. The evidence of linkage and association was markedly diminished after removing these 39 families from the analyses, thus providing support that GSTO1h drives the original linkage results. The maximum average AAO delayed by GSTO1h SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/-4.41) years for AD and 8.6(+/-5.71) for PD, respectively. This is comparable to the magnitude of AAO difference by APOE-4 in these same AD and PD families. These findings suggest the presence of genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in modifying AAO in these two disorders.

Background: Previous linkage studies have shown that chromosome 12 harbors susceptibility genes for late-onset Alzheimer disease (LOAD). However, association studies of several candidate genes on this chromosome region have produced ambiguous results. A recent study reported the association between the glyceraldehyde-3-phosphate dehydrogenase ( GAPD ) gene on chromosome 12p and the risk of LOAD. Methods: The authors conducted family-based and case-control association studies in two independent LOAD data sets on 12 single-nucleotide polymorphisms (SNPs) in the GAPD gene and its paralogs. Results: No association was found of the GAPD gene with LOAD in the family-based data set, but marginal evidence of association was seen in the later-onset subgroup when age at onset was stratified. The SNP rs2029721 in one GAPD pseudogene was also found to be associated with risk for LOAD in the unrelated case-control data set ( p = 0.003). Conclusions: The GAPD gene and its pseudogene may play a role in the development of late-onset Alzheimer disease. However, the effect, if any, is likely to be limited.

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0 years) completed a naloxone challenge and/or the modified Trier Social Stress Test (TSST). For the naloxone challenge, two baseline blood samples were obtained. Placebo was then administered (0 min), followed by increasing doses of intravenous naloxone (50, 100, 200 and 400 microg/kg) at 30-min intervals. Post-placebo blood samples were collected at 15-min intervals for 180 min. The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Eighty subjects (53 male, 27 female) underwent the TSST. Following the psychological stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly greater in male subjects compared to female subjects (z=-2.34, p=0.019 and z=-2.12, p=0.034, respectively). Seventy-two subjects (52 male, 20 female) underwent HPA axis activation induced by naloxone. In contrast to the TSST, cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=4.11, p

OBJECTIVE: To assess whether age at onset variation reflects underlying genetic heterogeneity in bipolar disorder, the authors examined the clinical and familial characteristics of age at onset in bipolar disorder subjects from families with multiple affected members. METHOD: A total of 211 families with 1,856 subjects were ascertained through bipolar I disorder probands. All the subjects were assessed with the Diagnostic Interview for Genetic Studies and assigned diagnoses by trained clinicians using best estimate procedures. Admixture analysis with the 211 bipolar disorder probands was used to decompose the age-at-onset distribution into a mixture of theoretical normal distributions. Logistic regression with general estimating equations was then used to examine clinical correlates and familial aggregation of age at onset in all 717 bipolar disorder subjects. RESULTS: The age-at-onset distribution consisted of a mixture of three normal distributions with means of 16.6 (SD=5.1), 26.0 (SD=1.4), and 34.7 (S...

We report here the first electrochemical oxidation−reduction cycle procedure to roughen gold substrates in 0.1 N HCl aqueous solution containing 1 mM rutile TiO2 nanoparticles under the irradiation of UV light. It is encouraging to find that the oxidized peak in the anodic scan, which is responsible for the surface-enhanced Raman scattering, increases significantly due to the effect of adding TiO2 under an electric field and UV irradiation. Moreover, the SERS spectrum of polypyrrole electrodeposited on the corresponding roughened gold substrate exhibits a 5-fold higher intensity compared to that without the contribution of TiO2 nanoparticles.

Carbon spheres with diameters between 400 and 2000 nm were synthesized in large quantities by catalytic chemical vapor deposition (CCVD) method using Kaolin supported transition metal salts (M=Fe, Co, Ni, etc.) as catalysts. The reaction conditions for the synthesis of carbon spheres in different sizes are described. The reactivity of the carbon spheres in various organic solvents is discussed. The as-synthesized carbon spheres are composed of unclosed graphene layers with the interlayer distances 0.33–0.35 nm. These carbon spheres have been characterized by SEM, TEM, HRTEM, XRD, Raman, ESR and SQUID magnetization techniques. From the ESR and SQUID the metallic nature of the carbon spheres is described.

Silicon nanowires (SiNWs, diameter ≥ 5 nm, and length ∼ μm) have been fabricated with metal- and SiO2-catalyses assisted by laser ablation. In the catalytic growth of single-crystalline SiNWs by pu...

Autism spectrum disorder (ASD) affects 1 in 68 children in the US and is distinguished by core deficits in social interactions. Developing pharmacologic treatments for ASD is complicated by clinical and genetic heterogeneity. Although pharmacological treatments have not been shown to be effective in treating the core symptoms of ASD (i.e., social deficits), there is evidence that the burden of emotional and behavioral problems can be reduced with pharmacotherapy. Numerous randomized clinical trials of treatments for the core ASD deficits have been conducted; however, most have provided inconclusive results due to the substantial variation in treatment response. Variation also exists in the considerable metabolic side effects of many of the current treatments. Some of this variation may be explained by differences in the underlying genetic pathways. Exploiting the link between genetic heterogeneity and clinical variation associated with behavioral problems may provide an opportunity for targeted treatment of ASD. In this review, we summarize the recent findings from pharmacogenomics studies of ASD and suggest further how understanding how genetic liability modifies the effect of drugs may present an opportunity to address the challenges of personalized medicine in autism.

Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset emotion dysregulation, the genetic basis for pediatric-onset emotion dysregulation remains elusive. The current review article presents a summary of previous studies that have suggested a few genetic variants associated with pediatric emotion dysregulation. Among these candidate loci, many prior studies have been focused on serotonin transporter promoter gene polymorphism 5-HTTLPR. Certain alleles of the 5-HTTLPR gene polymorphism have been found to be associated with traits associated with emotion dysregulation, such as aggression, affect reactivity, and insecure attachment. Additionally, genetic variants involving dopamine and neurophysiological biomarkers like the COMT Val158Met (rs460) and dopamine receptor D2/ ankyrin repeat and kinase domain containing one polymorphisms may play a role in emotion dysregulation. Inconsistent findings have been noted, possibly due to the heterogeneity in study designs and characteristics of different populations. Further research on the role of genetic predetermination of emotion dysregulation in children and adolescents is warranted.