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

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

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

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

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ≥17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted.Seaside Therapeutics Inc

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

Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months

Objective: Risperidone is effective for short-term treatment of aggression, temper outbursts, and self-injurious behavior in children with autism. Because these behaviors may be chronic, there is a need to establish the efficacy and safety of longer-term treatment with this agent. Method: The authors conducted a multisite, two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums, aggression, and/or self-injurious behavior who showed a positive response in an earlier 8-week trial. Part I consisted of 4-month open-label treatment with risperidone, starting at the established optimal dose; part II was an 8-week randomized, double-blind, placebo-substitution study of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale. Results: Part I included 63 children. The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment. The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant. Reasons for discontinuation of part I included loss of efficacy (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for gradual placebo substitution and 12.5% for continued risperidone; this difference was statistically significant. Conclusions: Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums, aggression, and/or self-injurious behavior. Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects