Moderators and Predictors of Response to Behavior Therapy for Tics in Tourette Syndrome

Objective: To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. Methods: Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9–69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression–Improvement score assessed by masked evaluators. Results: The presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction. Conclusions: Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication. ClinicalTrials.gov identifiers: The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively). Classification of evidence: This study provides Class I evidence that CBIT is effective in reducing tic severity across subgroups of patients with chronic tic disorders, although the difference between treatments was smaller for participants on tic-suppressing medications, suggesting reduced efficacy in this subgroup

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

Sustainable Campus Community Engagement

Laser metal deposition (LMD) was applied to deposit Inconel 718 metal matrix composites reinforced with TiC particles. The influence of laser energy input per unit length on constitution phases, microstructures, hardness, and wear performance of LMD-processed TiC/Inconel 718 composites was studied. It revealed that the LMD-processed composites consisted of γ Ni-Cr solid solution matrix, the intermetallic precipitation phase γ′, and the TiC reinforcing phase. For the laser energy input per unit length of 80-120 kJ/m, a coherent interfacial layer with the thickness of 0.8-1.4 μm was formed between TiC reinforcing particles and the matrix, which was identified as (Ti,M)C (M=Nb and Mo) layer. Its formation was due to the reaction of the strong carbide-forming elements Nb and Mo of the matrix with the dissolved Ti and C on the surface of TiC particles. The microstructures of the TiC reinforcing phase experienced a successive change as laser energy input per unit length increased: Relatively coarsened poly-angular particles (80 kJ/m) - surface melted, smoothened TiC particles (≥100 kJ/m) - fully melted/precipitated, significantly refined TiC dendrites/particles (160 kJ/m). Using the laser energy input per unit length ≥100 kJ/m produced the fully dense composites having the uniformly dispersed TiC reinforcing particles. Either the formation of reinforcement/matrix interfacial layer or the refinement in TiC dendrites/particles microstructures enhanced the microhardness and wear performance of TiC/Inconel 718 composites

First-principles phase diagram calculations for the HfC–TiC, ZrC–TiC, and HfC–ZrC solid solutions

We report first-principles phase diagram calculations for the binary systems HfC–TiC, TiC–ZrC, and HfC–ZrC. Formation energies for superstructures of various bulk compositions were computed with a plane-wave pseudopotential method. They in turn were used as a basis for fitting cluster expansion Hamiltonians, both with and without approximations for excess vibrational free energies. Significant miscibility gaps are predicted for the systems TiC–ZrC and HfC–TiC, with consolute temperatures in excess of 2000 K. The HfC–ZrC system is predicted to be completely miscibile down to 185 K. Reductions in consolute temperature due to excess vibrational free energy are estimated to be ~7%, ~20%, and ~0%, for HfC–TiC, TiC–ZrC, and HfC–ZrC, respectively. Predicted miscibility gaps are symmetric for HfC–ZrC, almost symmetric for HfC–TiC and asymmetric for TiC–ZrC

Deposition of Ti/TiC Composite Coatings on Implant Structures Using Laser Engineered Net Shaping

A new method of depositing hard and wear resistant composite coatings on metal-onmetal bearing surfaces of titanium implant structures is proposed and demonstrated. The method consists of depositing a Ti/TiC composite coating (~ 2.5 mm thick) on titanium implant bearing surfaces using Laser Engineered Net Shaping (LENS®). Defect-free composite coatings were successfully produced at various amounts of the reinforcing TiC phase with excellent interfacial characteristics using a mixture of commercially pure Ti and TiC powders. The coatings consisted of a mixture of coarser unmelted/partially melted (UMC) TiC particles and finer, discreet resolidified (RSC) TiC particles uniformly distributed in the titanium matrix. The amounts of UMC and RSC were found to increase with increasing TiC content of the original powder mixture. The coatings exhibited a high level of hardness, which increased with increasing TiC content of the original powder mixture. Fractographic studies indicated that the coatings, even at 60 vol.% TiC, do not fail in a brittle manner. Various aspects of LENS® deposition of Ti/TiC composite coatings are addressed and a preliminary understanding of structure-property-fracture correlations is presented. The current work shows that the proposed approach to deposit composite coatings using laser-based metal deposition processes is highly-effective, which can be readily utilized on a commercial basis for manufacture of high-performance implants.Mechanical Engineerin

Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

Objective: Tourette’s syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette’s syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette’s syndrome polygenic risk to test whether Tourette’s and related tic disorders have an underlying shared genetic etiology and whether Tourette’s polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity. Methods: GWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette’s syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette’s polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined. Results: GWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette’s syndrome heritability. Tourette’s-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette’s PRS significantly predicted both Tourette’s syndrome and tic spectrum disorders status in the population-based sample. Tourette’s PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects. Conclusions: Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette’s syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette’s syndrome and other tic disorders in future diagnostic schemata. Tourette’s PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity

Benchmarking Treatment Response in Tourette’s Disorder: A Psychometric Evaluation and Signal Detection Analysis of the Parent Tic Questionnaire

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions – Improvement (CGI-I) scale. Cronbach’s alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment

Incorporation of TiC particles on AlSi 4340 low alloy steel surfaces via tungsten inert gas melting

Surface cladding utilizes a high energy input to deposit a layer on substrate surfaces providing protection against wear and corrosion. In this work, TiC particulates were incorporated by melting single tracks in powder preplaced onto AISI 4340 low alloy steel surfaces using a Tungsten Inert Gas (TIG) torch with a range of processing conditions. The effects of energy input and powder content on the melt geometry, microstructure and hardness were investigated. The highest energy input (1680J/mm) under the TIG torch produced deeper (1.0 mm) and wider melt pools, associated with increased dilution, compared to that processed at the lowest energy (1008J/mm). The melt microstructure contained partially melted TiC particulates associated with dendritic, cubic and globular type carbides precipitated upon solidification of TiC dissolved in the melt; TiC accumulated more near to the melt-matrix interface and at the track edges. Addition of 0.4, 0.5 and 1.0 mg/mm2 TiC gave hardness values in the resolidified melt pools between 750 to over 1100Hv, against a base hardness of 300 Hv; hardness values are higher in tracks processed with a grcater TiC addition and reduced energy input

Subjective versus Objective Measures of Tic Severity in Tourette Syndrome – The Influence of Environment

The objective of this study was to examine the influence of environmental challenges on tic expression by subjective and objective measures. The study group consisted of 41 children aged 6–18 years (M=10.15, SD=2.73) with a primary diagnosis of Tourette syndrome. Subjective measures included the Functional Assessment Interview developed for this study and three standard validated instruments. The objective measure was a video-recording of the patients in five daily-life situations: watching television, doing homework, being alone, receiving attention when ticcing, and talking to a stranger. In addition, the effect of premonitory urges on assessment of tic expression was evaluated. The associations between the subjective and objective measures of tic expression were moderate to low. A significantly higher number of tics were observed in the television situation, and a significantly lower number in the alone situation, compared to the other situations. Higher levels of premonitory urge were associated with greater awareness of objectively measured tic expression. In conclusion, tic expression is significantly influenced by the environment. Subjective measures of tic expression may be misleading. These results have implications for refining the clinical assessment of tics, improving research methodology, and developing new therapeutic strategies