1. Cicchetti DV, Koenig K, Klin A, Volkmar FR, Paul R, Sparrow S. {{From Bayes Through Marginal Utility to Effect Sizes: A Guide to Understanding the Clinical and Statistical Significance of the Results of Autism Research Findings}}. {J Autism Dev Disord} (May 19)
The objectives of this report are: (a) to trace the theoretical roots of the concept clinical significance that derives from Bayesian thinking, Marginal Utility/Diminishing Returns in Economics, and the « just noticeable difference », in Psychophysics. These concepts then translated into: Effect Size (ES), strength of agreement, clinical significance, and related concepts, and made possible the development of Power Analysis; (b) to differentiate clinical significance from statistical significance; and (c) to demonstrate the utility of measures of ES and related concepts for enhancing the meaning of Autism research findings. These objectives are accomplished by applying criteria for estimating clinical significance, and related concepts, to a number of areas of autism research.
2. Gaita L, Manzi B, Sacco R, Lintas C, Altieri L, Lombardi F, Pawlowski TL, Redman M, Craig DW, Huentelman MJ, Ober-Reynolds S, Brautigam S, Melmed R, Smith CJ, Marsillach J, Camps J, Curatolo P, Persico AM. {{Decreased serum arylesterase activity in autism spectrum disorders}}. {Psychiatry Res} (May 18)
The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10(-)(16)). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84×10(-)(16)). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.
3. Russell PS, Daniel A, Russell S, Mammen P, Abel JS, Raj LE, Shankar SR, Thomas N. {{Diagnostic accuracy, reliability and validity of Childhood Autism Rating Scale in India}}. {World J Pediatr} (May);6(2):141-147.
BACKGROUND: Since there is no established measure for autism in India, we evaluated the diagnostic accuracy, reliability and validity of Childhood Autism Rating Scale (CARS). METHODS: Children and adolescents suspected of having autism were identified from the unit’s database. Scale and item level scores of CARS were collected and analyzed. Sensitivity, specificity, likelihood ratios and predictive values for various CARS cut-off scores were calculated. Test-retest reliability and inter-rater reliability of CARS were examined. The dichotomized CARS score was correlated with the ICD-10 clinical diagnosis of autism to establish the criterion validity of CARS as a measure of autism. Convergent and divergent validity was calculated. The factor structure of CARS was demonstrated by principal components analysis. RESULTS: A CARS score of >/=33 (sensitivity = 81.4%, specificity = 78.6%; area under the curve = 81%) was suggested for diagnostic use in Indian populations. The inter-rater reliability (ICC=0.74) and test-retest reliability (ICC=0.81) for CARS were good. Besides the adequate face and content validity, CARS demonstrated good internal consistency (Cronbach’s alpha=0.79) and item-total correlation. There was moderate convergent validity with Binet-Kamat Test of Intelligence or Gessell’s Developmental Schedule (r=0.42; P=0.01), divergent validity (r=-0.18; P=0.4) with ADD-H Comprehensive Teacher Rating Scale, and high concordance rate with the reference standard, ICD-10 diagnosis (82.52%; Cohen’s kappa=0.40, P=0.001) in classifying autism. A 5-factor structure explained 65.34% of variance. CONCLUSION: The CARS has strong psychometric properties and is now available for clinical and research work in India.
