Defining Expressive Language Benchmarks for Children with Down Syndrome.

Establishing expressive language benchmarks (ELBs) for children with Down syndrome (DS), as developed by Tager-Flusberg et al. for children with autism, is critically needed to inform the development of novel treatments, identify individualized treatment targets, and promote accurate monitoring of progress. In the present study, we assessed ELB assignments in three language domains (phonology, vocabulary, and grammar) for 53 young children with DS (CA range: 2.50-7.99 years) using standardized assessments. The participants were classified into one of four ELB levels (preverbal, first words, word combinations, and sentences) in each language domain. Associations with additional measures of language, chronological age, nonverbal cognition, and verbal short-term memory were considered. Analyses of individual ELB profiles indicated substantial variability across the three language domains, with six different patterns of variation across domains emerging. At the same time, the ELB categories were significantly associated with independent language measures and broader developmental domains. Moreover, ELB changes were observed in a small sample of children with DS reassessed 18-24 months after the initial visit. Results from the present study suggest the procedures outlined by Tager-Flusberg et al. for defining ELBs are a potentially useful tool for describing the language abilities of children with DS.

Executive function as measured by the Behavior Rating Inventory of Executive Function-2: children and adolescents with Williams syndrome.

BACKGROUND: Difficulties with executive functions (EF) are very common among individuals with Williams syndrome (WS). To characterise the pattern of relative strengths and weaknesses in EF for children and adolescents with WS, we considered the performance of a large sample on the parent version of the Behavior Rating Inventory of Executive Function-2 (BRIEF-2). Associations between distinct components of EF and adaptive behaviour, behaviour problems and intellectual ability were investigated. The concurrent effects of components of behaviour regulation and emotion regulation on attention problems and anxiety problems also were evaluated. METHODS: Participants were 308 6-17-year-olds with genetically confirmed classic WS deletions. Parent report of EF was measured by the BRIEF-2 questionnaire. Most participants (223/308) completed the Differential Ability Scales-II as a measure of intellectual ability. The parents of these individuals also completed the Child Behavior Checklist and the interview form of the Scales of Independent Behavior-Revised. RESULTS: As a group, the participants evidenced considerable parent-reported EF difficulty. A profile of relative strength and weakness was found at the index level, with performance on both the Behavior Regulation Index and the Emotion Regulation Index significantly better than performance on the Cognitive Regulation Index. Within each index, a statistically significant pattern of relative strength and weakness also was identified. Difficulties with behaviour regulation and emotion regulation were related to both behaviour problems and adaptive behaviour limitations. Higher inflexibility and more difficulty with self-monitoring were associated with lower overall intellectual ability. Difficulty with inhibition was uniquely associated with attention problems, and inflexibility was uniquely associated with anxiety problems. CONCLUSIONS: Executive function difficulties are highly prevalent among children and adolescents with WS and are associated with adaptive behaviour limitations, both internalising and externalising behaviour problems and more limited intellectual ability. These results highlight the importance of designing and delivering research-based interventions to improve the EF of children and adolescents with WS.

Predictors of specific phobia in children with Williams syndrome.

BACKGROUND: Specific phobia (SP) is the most common anxiety disorder among children with Williams syndrome (WS); prevalence rates derived from Diagnostic and Statistical Manual of Mental Disorders-based diagnostic interviews range from 37% to 56%. We evaluated the effects of gender, age, intellectual abilities and/or behaviour regulation difficulties on the likelihood that a child with WS would be diagnosed with SP. METHODS: A total of 194 6-17 year-olds with WS were evaluated. To best characterise the relations between the predictors and the probability of a SP diagnosis, we explored not only possible linear effects but also curvilinear effects. RESULTS: No gender differences were detected. As age increased, the likelihood of receiving a SP diagnosis decreased. As IQ increased, the probability of receiving a SP diagnosis also decreased. Behaviour regulation difficulties were the strongest predictor of a positive diagnosis. A quadratic relation was detected: The probability of receiving a SP diagnosis gradually rose as behaviour regulation difficulties increased. However, once behaviour regulation difficulties approached the clinical range, the probability of receiving a SP diagnosis asymptoted at a high level. CONCLUSION: Children with behaviour regulation difficulties in or just below the clinical range were at the greatest risk of developing SP. These findings highlight the value of large samples and the importance of evaluating for nonlinear effects to provide accurate model specification when characterising relations among a dependent variable and possible predictors.

Performance on the Kaufman Brief Intelligence Test-2 by Children With Williams Syndrome.

We describe the performance of 292 4- to 17-year-olds with Williams syndrome (WS) on the Kaufman Brief Intelligence Test-2 (KBIT-2; Kaufman & Kaufman, 2004). Mean IQ Composite, Verbal standard score (SS), and Nonverbal SS were in the borderline range relative to the general population, with variability similar to the general population. Correlations between SSs and CA were close to 0, with no significant sex differences. There was a significant effect of maternal education on Verbal SS. The KBIT-2 appropriately captures the full range of performance of 8- to 17-year-olds with WS for the abilities measured and of all but the very lowest-functioning 5- to 7-year-olds. However, the KBIT-2 does not contain easy enough items to adequately assess the abilities of the lowest quartile of 4-year-olds.

Children with Williams syndrome: Developmental trajectories for intellectual abilities, vocabulary abilities, and adaptive behavior.

To examine longitudinal trajectories of intellectual abilities, single-word vocabulary abilities, and adaptive behavior for 76 children with Williams syndrome (WS) aged 4-15 years, we compared their standard scores (SSs) at two time points approximately 3 years apart on the same standardized measures. At the group level, mean SS declined significantly for 8 of the 12 measures and showed a slight (nonsignificant) increase or decrease for 4 measures. However, for most measures significant changes in SS were found for only a small proportion of the children, with some children evidencing significant declines and a smaller proportion evidencing significant increases. Significant SS changes were most common for adaptive behavior. For all measures, the mean magnitude of SS change was smaller for older children (>7.5 years at Time 1) than for younger children (<7.5 years at Time 1). Furthermore, correlations between Time 1 and Time 2 SSs were larger for the older cohort than for the younger cohort, indicating that SS stability was greater for older children than for younger children. Although mean SSs declined for most measures, indicating that children with WS as a group were not making the expected amount of progress relative to their general population peers who earned the same SS at Time 1, there was little evidence either of regression (loss of skills) or stagnation (failure to increase raw scores). The relations of these results to those of previous smaller-sample longitudinal studies of children with WS and the implications of the findings are considered.

Children with 7q11.23 duplication syndrome: psychological characteristics.

To begin to delineate the psychological characteristics associated with classic 7q11.23 duplication syndrome (duplication of the classic Williams syndrome region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged 4-17 years. Sixteen toddlers aged 18-45 months with classic Dup7 and 12 adults identified by cascade testing also were assessed. For the child group, median General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II was 85.0 (low average), with a range from severe disability to high average ability. Median reading and mathematics achievement standard scores were at the low average to average level, with a range from severe impairment to high average or superior ability. Adaptive behavior was considerably more limited; median Scales of Independent Behavior-Revised Broad Independence standard score was 62.0 (mild impairment), with a range from severe adaptive impairment to average adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the children screened positive for a possible Autism Spectrum Disorder and 82.3% were diagnosed with Speech Sound Disorder. We compare these findings to previously reported results for children with Williams syndrome and argue that genotype/phenotype studies involving the Williams syndrome region offer important opportunities to understand the contribution of genes in this region to common disorders affecting the general population.

Enumeration of small and large numerosities: the effect of element visibility.

Precise enumeration is associated with small numerosities within the subitizing range (<4 items), while approximate enumeration is associated with large numerosities (>4 items). To date, there is still debate on whether a single continuous process or dual mutually exclusive processes mediate enumeration of small and large numerosities. Here, we evaluated a compromise between these two notions: that the precise representation of number is limited to small numerosities, but that the approximate representation of numerosity spans across both small and large numerosities. We assessed the independence of precise and approximate enumeration by looking at how luminance contrast affected enumeration of elements that differ by ones (1-8) or by tens (10-80). We found that enumeration functions of ones and tens have different characteristics, which is consistent with the presence of two number systems. Subitizing was preserved for small numerosities. However, simply decreasing element visibility changed the variability signatures of small numerosities to match those of large numerosities. Together, our results suggest that small numerosities are mediated by both precise and approximate representations of numerosity.

Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and imipramine with that of placebo in the treatment of bipolar depression in adult outpatients stabilized on a regimen of lithium. METHOD: In a double-blind, placebo-controlled study, 117 outpatients with DSM-III-R bipolar disorder, depressive phase, were randomly assigned to treatment with paroxetine (N=35), imipramine (N=39), or placebo (N=43) for 10 weeks. In addition to lithium monotherapy, patients may have received either carbamazepine or valproate in combination with lithium for control of manic symptoms. Patients were stratified on the basis of trough serum lithium levels determined at the screening visit (high: >0.8 meq/liter; low:

Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.

BACKGROUND: The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined. RESULTS: 307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment.

Interaction energy analyses of folate analog binding to human dihydrofolate reductase: contribution of the antifolate substructural regions to complex stability.

The three-dimensional structure of the human dihydrofolate reductase (DHFR), methotrexate tetrazole, and NADPH ternary complex was used to model the corresponding ternary complexes with methotrexate tetrazole replaced by methotrexate, methotrexate-polyglutamate with three glutamyl residues, and 5,10-deazaaminopterin, respectively. Each complex was solvated in a 60-angstrom cube of explicit water and subjected to structural minimization followed by interaction energy analyses. Interaction energy calculations were performed for the antifolate interaction with water, NADPH, the DHFR binding site residues, the entire DHFR protein, and the solvated NADPH:DHFR complex. These studies revealed that methotrexate-polyglutamate exhibited the most stable interactions and that approximately one half of antifolate:DHFR stability could be accounted for by the interaction of the antifolate with the binding site residues. The antifolate structures were also subdivided into heterocyclic, phenyl, and glutamyl substructural regions. Interaction energies were subsequently calculated for the interactions of the subregions with water, NADPH, the DHFR binding site residues, the DHFR protein, and the solvated NADPH:DHFR complex. The glutamyl substructural region showed the greatest contribution to overall antifolate binding stability due to its interaction with the DHFR protein. The heterocyclic and phenyl substructural regions generally showed much less stable interactions. These results suggest that the primary stabilizing factor of the antifolate interaction is the interaction of glutamyl with the DHFR protein. Additionally, interaction energy analyses were performed for specific groups of atoms within the substructural regions. These studies indicated that the stability of the glutamyl interaction is due to the interaction of glutamyl oxygen atoms with the DHFR protein. In the case of the methotrexate tetrazole complex, the tetrazole nitrogens also contribute significantly to the stability of the glutamyl interaction. The carbon atoms of the heterocyclic and phenyl groups both showed more stable interactions with NADPH than with water, while the nitrogen atoms showed more stable interactions with water than with NADPH. Collectively, these results indicate that the glutamyl region is the most important in antifolate binding stability.

Reservoir competence of Carcinops pumilio for Salmonella enteritidis (Eubacteriales: Enterobacteriaceae).

The histerid beetle Carcinops pumilio (Erichson) occurs naturally in poultry house manure and is an important predator of house fly eggs and larvae. Because efforts to commercially produce C. pumilio have been unsuccessful, one fly control strategy under consideration is the direct transport of adult C. pumilio between poultry houses to facilitate their establishment. However, we demonstrate that C. pumilio is a competent reservoir of Salmonella enteritidis (Gaertner). Adult C. pumilio exposed to S. enteritidis-inoculated house fly eggs harbored the bacterium externally and internally for up to 4 and 13 d, respectively, and feces were culture-positive for S. enteritidis for at least 14 d. This suggests that C. pumilio can be a reservoir of S. enteritidis; therefore its movement between poultry facilities should be carefully considered.

Spatio-temporal dynamics of resident and immigrating populations of Carcinops pumilio (Coleoptera: Histeridae) in high-rise poultry facilities.

The histerid beetle Carcinops pumilio (Erichson) is an important natural predator of the house fly, Musca domestica L., in accumulated poultry house manure. We examined the spatio-temporal dynamics of establishing adult C. pumilio in high-rise poultry facilities using conventional and geostatistical approaches. The growth curves of resident and immigrating populations followed logistic and exponential equations, respectively, and their rates of establishment were statistically the same. Frequency distributions for both populations were strongly positively skewed, and approximately 53% of sampling intervals were significantly modeled by the negative binomial. Taylor's power law indicated both populations to be aggregated, and gave excellent least squares regression fits to both populations. Correlograms, a geostatistical tool, suggested little local spatial structure (e.g., 2nd order effects) for either population. The resident population was 'randomly' aggregated: beetles were clustered around randomly distributed aggregations of house fly immatures. The immigrating population exhibited significant spatial trends (e.g., 1st order effects) consistently seen at all sampling intervals. C. pumilio spatial structure was represented primarily by this spatial trend; thus, immigration of C. pumilio may have been either a singular event in time, or initiating at 1 or multiple times from a singular location.

Flotation method for extracting insects from poultry manure samples.

We examined the efficacy of a sucrose-based flotation method for extracting 3 prevalent insect species from poultry house manure: 3rd-instar Musca domestica L. (Diptera: Muscidae), Carcinops pumilio (Erichson) (Coleoptera: Histeridae) adults, and Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) adults. A 0.6 M sucrose solution in distilled water altered the specific gravity to 1.2 and caused the 3 species to float to the water surface for easy separation. An analysis of variance (ANOVA) showed significant effects of the solution volume to sample mass ratio on recovery rates (F = 35.96, P < 0.0001), but no differences in species-specific recovery rates (F = 0.97, P = 0.3824). Among samples agitated in a ratio of at least 3.2 ml solution per gram of sample mass, we observed neither significant ratio effects (F = 1.37, P = 0.2442) nor significant differences in species-specific recovery rates (F = 2.05, P = 0.1353); overall, we recovered 97.49 +/- 0.20% of all individuals of the 3 species. Our analyses demonstrated that sucrose-based flotation was a statistically valid method of collecting these species from poultry manure samples.

Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.

CONTEXT: The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use. OBJECTIVE: To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia. DESIGN: Twelve-week, multicenter, randomized, double-blind trial. SETTING: Thirteen centers across the United States and 1 in Canada. PARTICIPANTS: Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment. INTERVENTION: After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment. MAIN OUTCOME MEASURES: Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score. RESULTS: Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine. CONCLUSIONS: Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.

Measurement of cytosolic Ca2+ concentration in Limulus ventral photoreceptors using fluorescent dyes.

Several Ca-sensitive fluorescent dyes (fura-2, mag-fura-2 and Calcium Green-5N) were used to measure intracellular calcium ion concentration, Cai, accompanying light-induced excitation of Limulus ventral nerve photoreceptors. A ratiometric procedure was developed for quantification of Calcium Green-5N fluorescence. A mixture of Calcium Green-5N and a Ca-insensitive dye, ANTS, was injected in the cell and the fluorescence intensities of both dyes were used to calculate the spatial average of Cai within the light-sensitive R lobe of the photoreceptor. In dark-adapted photoreceptors, the initial Cai was 0.40 +/- 0.22 microM (SD, n = 7) as measured with fura-2. Cai peaked in the light-sensitive R lobe at 700-900 ms after the onset of an intense measuring light step, when the spatial average of Cai within the R lobe reached 68 +/- 14 and 62 +/- 37 microM (SD, n = 5) as measured with mag-fura-2 and Calcium Green-5N, respectively. The rate of Cai rise was calculated to be approximately 350 microM/s under the measuring conditions. The resting level of Mg2+ was estimated to be 1.9 +/- 0.9 mM, calculated from mag-fura-2 measurements. To investigate the effect of adapting light on the initial Cai level in the R lobe, a 1-min step of 420 nm background light was applied before each measurement. The first significant (P < 0.05) change in the initial level of Cai occurred even at the lowest adapting light intensity, which delivered approximately 3 x 10(3) effective photons/s. The relative sensitivity of the light-adapted photoreceptors was linearly related to the relative Cai on a double log plot with slope between -4.3 and -5.3. We were unable to detect a Cai rise preceding the light-activated receptor potential. The Cai rise, measured with Calcium Green-5N, lagged 14 +/- 5 ms (SD, n = 32) behind the onset of the receptor potential at room temperature in normal ASW. In the absence of extracellular Ca2+ and at 10 degrees C, this lag increased to 44 +/- 12 ms (SD, n = 17).

Self-denigratory beliefs following sexual abuse: association with the symptomatology of bulimic disorders.

Reported sexual abuse is associated with bulimic symptomatology. It has been suggested that this association might be due to impaired self-esteem. However, from the evidence to date, it appears that general self-esteem may be too "blunt" a construct, and that more specific psychological mediators need to be considered. This study compares the values of a measure of general self-esteem and a measure of specific self-denigratory beliefs consequent upon sexual abuse in predicting levels of eating psychopathology in eating-disordered women. Self-esteem was associated with the level of general eating attitudes, whereas specific self-denigratory beliefs were associated with the frequency of vomiting. Neither variable adequately predicted the frequency of binging.

Emotional crying, depressed mood, and secretory immunoglobulin A.

The relationship between emotional crying and secretory immunoglobulin A (S-IgA) in whole saliva was examined. Previous research had indicated that lower S-IgA was associated with crying. Similar results were found in the present study. Depressed mood was not associated with S-IgA.

Flight behavior of Musca domestica and Stomoxys calcitrans (Diptera: Muscidae) in a Kansas dairy barn.

Aerial density, flight thresholds, and periodicity were estimated for the house fly, Musca domestica L., and the stable fly, Stomoxys calcitrans (L.), from data collected by suction traps located in a dairy barn in Kansas between 1 July and 31 October 1970. M. domestica catches increased from July to August, declining to near zero by the end of October. S. calcitrans catches peaked in July and September with a major decline in August. Both species exhibited a diel periodicity in flight with maximal activity during the early afternoon. Secondary peaks were detected in the late afternoon or early evening. M. domestica activity peaked about two hours after S. calcitrans. Male and female S. calcitrans flight activity patterns were slightly different, but peaked at the same time. Both species flew at temperatures between 20 and 38 degrees C. At temperatures over 33 degrees C, stable fly activity decreased rapidly. No upper threshold for flight by M. domestica was detected. The median temperature-flight thresholds of male and female S. calcitrans were significantly different, with females flying at lower temperatures than males. The threshold for M. domestica flight was lower than for S. calcitrans. The shape of the temperature-flight relationship indicated that the flight threshold was determined by heat accumulation.