Elevated Thyroid Indices in Children and Adolescents with Obsessive-Compulsive Disorder: Effects of Clomipramine Treatment

Objective: To examine the basal thyroid function in pediatric Obsessive Compulsive Disorder (OCD) versus controls, and to explore the relation between baseline thyroid measures and response to clomipramine treatment, and the effects of treatment on thyroid hormones. Methods: Sixteen children and adolescents with DSM-III-R OCE and 13 control children and adolescents without psychiatric illness were compared on basal measures of thyroidstimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). For the OCD subjects, samples were compared pre- and post- 4 weeks of treatment with clomipramine. Response of OCD symptoms was measured by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Results: OCD subjects demonstrated subtle but significant elevations of TSH, T3, and T4 pre-treatment compared to controls. Clomipramine treatment was associated with significant decreases in TSH and T3 concentrations. Pre-treatment TSH and T4 concentrations correlated with reductions in CY-BOCS following 8 weeks of clomipramine. Conclusion: Elevated thyroid function at baseline may be a biomarker of OCD improvement, and may reflect aspects of the underlying pathophysiology of OCD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63200/1/cap.2005.15.581.pd

A Multicenter Examination and Strategic Revisions of the Yale Global Tic Severity Scale

Objective To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure. Methods This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points. Results Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference. Conclusions The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed

Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD

openWAR: An Open Source System for Evaluating Overall Player Performance in Major League Baseball

Within baseball analytics, there is substantial interest in comprehensive statistics intended to capture overall player performance. One such measure is Wins Above Replacement (WAR), which aggregates the contributions of a player in each facet of the game: hitting, pitching, baserunning, and fielding. However, current versions of WAR depend upon proprietary data, ad hoc methodology, and opaque calculations. We propose a competitive aggregate measure, openWAR, that is based upon public data and methodology with greater rigor and transparency. We discuss a principled standard for the nebulous concept of a "replacement" player. Finally, we use simulation-based techniques to provide interval estimates for our openWAR measure.Comment: 27 pages including supplemen

An exploration of concomitant psychiatric disorders in children with autism spectrum disorder

Objective We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD). Methods Participants were 658 children with ASD (age 3–17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics. Results Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented. Conclusion In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity

A Prospective Open Trial of Guanfacine in Children with Pervasive Developmental Disorders

Objective: A common complaint for children with pervasive developmental disorder (PDD) is hyperactivity. The purpose of this pilot study was to gather preliminary information on the efficacy of guanfacine in children with PDD and hyperactivity. Methods: Children with PDD accompanied by hyperactivity entered the open-label trial if there was a recent history of failed treatment with methylphenidate or the child did not improve on methylphenidate in a multisite, placebo-controlled trial. Results: Children (23 boys and 2 girls) with a mean age of 9.03 (±3.14) years entered the open-label trial. After 8 weeks of treatment, the parent-rated Hyperactivity subscale of the Aberrant Behavior Checklist (ABC) went from a mean of 31.3 (±8.89) at baseline to 18.9 (±10.37) (effect size = 1.4; p < 0.001). The teacher-rated Hyperactivity subscale decreased from a mean of 29.9 (±9.12) at baseline to 22.3 (±9.44) (effect size = 0.83; p < 0.01). Twelve children (48%) were rated as Much Improved or Very Much Improved on the Clinical Global Impressions– Improvement. Doses ranged from 1.0 to 3.0 mg/day in two or three divided doses. Common adverse effects included irritability, sedation, sleep disturbance (insomnia or midsleep awakening), and constipation. Irritability led to discontinuation in 3 subjects. There were no significant changes in pulse, blood pressure, or electrocardiogram. Conclusions: Guanfacine may be useful for the treatment of hyperactivity in children with PDD. Placebocontrolled studies are needed to guide clinical practice

Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study

Background Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. Methods We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. Results Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). Conclusions The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made

The XMM-Newton Wide field survey in the COSMOS field: redshift evolution of AGN bias and subdominant role of mergers in triggering moderate luminosity AGN at redshift up to 2.2

We present a study of the redshift evolution of the projected correlation function of 593 X-ray selected AGN with I_AB<23 and spectroscopic redshifts z<4, extracted from the 0.5-2 keV X-ray mosaic of the 2.13 deg^2 XMM-COSMOS survey. We introduce a method to estimate the average bias of the AGN sample and the mass of AGN hosting halos, solving the sample variance using the halo model and taking into account the growth of the structure over time. We find evidence of a redshift evolution of the bias factor for the total population of XMM-COSMOS AGN from b(z=0.92)=2.30 +/- 0.11 to b(z=1.94)=4.37 +/- 0.27 with an average mass of the hosting DM halos logM [h^-1 M_sun] ~ 13.12 +/- 0.12 that remains constant at all z < 2. Splitting our sample into broad optical lines AGN (BL), AGN without broad optical lines (NL) and X-ray unobscured and obscured AGN, we observe an increase of the bias with redshift in the range z=0.7-2.25 and z=0.6-1.5 which corresponds to a constant halo mass logM [h^-1 M_sun] ~ 13.28 +/- 0.07 and logM [h^-1 M_sun] ~ 13.00 +/- 0.06 for BL /X-ray unobscured AGN and NL/X-ray obscured AGN, respectively. The theoretical models which assume a quasar phase triggered by major mergers can not reproduce the high bias factors and DM halo masses found for X-ray selected BL AGN with L_BOL ~ 2e45 erg s^-1. Our work extends up to z ~ 2.2 the z <= 1 statement that, for moderate luminosity X-ray selected BL AGN, the contribution from major mergers is outnumbered by other processes, possibly secular such as tidal disruptions or disk instabilities.Comment: 16 emulateapj pages, 18 figures and 3 tables. Accepted for the publication in The Astrophysical Journa