Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.

We assessed the spoken language of 73 preschool aged children on the autism spectrum receiving community-based early intervention at two time points, approximately 7 months apart. Using the Spoken Language Benchmarks, there was a small non-significant change in the proportion of children transitioning from below, to at or above, Phase 3 (word combinations). Using binomial regression, a model comprising seven of nine clinician-proposed child-related predictors explained 64% of the variance. None of the predictors were individually significant, although a large effect size (OR = 16.71) was observed for children's baseline rate of communicative acts. The findings point to substantial unmet clinical need in children with minimal verbal language, but also the relevance of clinician-proposed predictors of their spoken language outcomes.

Clinician Proposed Predictors of Spoken Language Outcomes for Minimally Verbal Children with Autism Spectrum Disorder.

Our aim was to explore insights from clinical practice that may inform efforts to understand and account for factors that predict spoken language outcomes for children with Autism Spectrum Disorder who use minimal verbal language. We used a qualitative design involving three focus groups with 14 speech pathologists to explore their views and experiences. Using the Framework Method of analysis, we identified 9 themes accounting for 183 different participant references to potential factors. Participants highlighted the relevance of clusters of fine-grained social, communication, and learning behaviours, including novel insights into prelinguistic vocal behaviours. The participants suggested the potential value of dynamic assessment in predicting spoken language outcomes. The findings can inform efforts to developing clinically relevant methods for predicting children's communication outcomes.

Soft Sensor-Based Monitoring and Efficient Control Strategies of Biomass Concentration for Continuous Cultures of Haloferax mediterranei and Their Application to an Industrial Production Chain.

Continuous bioprocessing using cell retention allows the achievement of high space-time yields for slow-growing organisms such as halophiles. However, the lack of efficient methods for monitoring and control limits the application of biotechnological processes in the industry. The aim of this study was to implement a control and online monitoring strategy for biomass in continuous cultures. For the first time, a feedforward cultivation strategy in a membrane-based cell retention system allowed to control the biomass concentration of the extreme halophilic Haloferax mediterranei at defined levels. Moreover, soft sensor-based biomass estimation allowed reliable monitoring of biomass online. Application of the combined monitoring and control strategy using industrial process water containing formate, phenol, aniline and 4,4'-methylenedianiline could for the first time demonstrate high throughput degradation in this extremophilic bioremediation process, obtaining degradation efficiencies of up to 100%. This process demonstrates the usefulness of continuous halophilic cultures in a circular economy application.

When Nonresponse Mechanisms Change: Effects on Trends and Group Comparisons in International Large-Scale Assessments.

Mechanisms causing item nonresponses in large-scale assessments are often said to be nonignorable. Parameter estimates can be biased if nonignorable missing data mechanisms are not adequately modeled. In trend analyses, it is plausible for the missing data mechanism and the percentage of missing values to change over time. In this article, we investigated (a) the extent to which the missing data mechanism and the percentage of missing values changed over time in real large-scale assessment data, (b) how different approaches for dealing with missing data performed under such conditions, and (c) the practical implications for trend estimates. These issues are highly relevant because the conclusions hold for all kinds of group mean differences in large-scale assessments. In a reanalysis of PISA (Programme for International Student Assessment) data from 35 OECD countries, we found that missing data mechanisms and numbers of missing values varied considerably across time points, countries, and domains. In a simulation study, we generated data in which we allowed the missing data mechanism and the amount of missing data to change over time. We showed that the trend estimates were biased if differences in the missing-data mechanisms were not taken into account, in our case, when omissions were scored as wrong, when omissions were ignored, or when model-based approaches assuming a constant missing data mechanism over time were used. The results suggest that the most accurate estimates can be obtained from the application of multiple group models for nonignorable missing values when the amounts of missing data and the missing data mechanisms changed over time. In an empirical example, we furthermore showed that the large decline in PISA reading literacy in Ireland in 2009 was reduced when we estimated trends using missing data treatments that accounted for changes in missing data mechanisms.

Kidney-specific deletion of multidrug resistance-related protein 2 does not aggravate acute cyclosporine A nephrotoxicity in rats.

OBJECTIVE: Multidrug resistance-related protein 2 (Mrp2) is expressed in apical membranes of renal proximal tubular cells and contributes to the renal secretion of cyclosporine A (CsA). Mrp2⁻/⁻ deficiency may lead to local renal CsA accumulation. We investigated whether kidney-specific Mrp2 deficiency enhances acute CsA nephrotoxicity in rats. METHODS: Kidney-specific Mrp2 deletion was achieved by bilateral nephrectomy and transplantation of a congenic Mrp2-deficient kidney into wild-type recipients. Controls received a wild-type kidney. Animals were treated with CsA (10 or 30 mg/kg/day) for 7 days. Renal hemodynamics and renal cortical mRNA expression profile, oxidative stress, and the abundance of multidrug resistance protein 1 (Mdr1) and Mrp2 were assessed. RESULTS: CsA accumulation and CsA-induced reduction in glomerular filtration rate were similar in wild-type and Mrp2⁻/⁻ kidneys. Renal vascular resistance and agonist-induced renal vascular responses were similar in both groups. A PCR array on 84 genes involved in the biotransformation and antioxidant defense revealed increased CsA-induced mRNA expression of genes involved in oxidative and metabolic stress, inflammation, and apoptosis. This gene expression pattern was similar in wild-type and Mrp2⁻/⁻ kidneys. CsA increased the renal cortical oxidized glutathione, did not affect xanthine oxidase-dependent superoxide formation, and decreased renal cortical NADPH oxidase-dependent superoxide formation. Furthermore, CsA increased Mdr1 protein abundance to a greater extent in Mrp2⁻/⁻ than in wild-type kidneys. CONCLUSION: Mrp2 is not critical for renal CsA disposition and its deficiency does not enhance acute CsA nephrotoxicity. The high Mdr1 abundance may at least in part prevent exaggerated CsA accumulation in Mrp2⁻/⁻ kidneys.

Language development and everyday functioning of children with hearing loss assessed at 3 years of age.

This paper reports language ability and everyday functioning of 133 children with hearing impairment who were evaluated at 3 years of age, as part of the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study. The language abilities of children were evaluated using the Preschool Language Scale (PLS-4), Peabody Picture Vocabulary Test (PPVT), Diagnostic Evaluation of Articulation and Phonology (DEAP) and Child Development Inventory (CDI). Everyday functioning of children was evaluated by interviewing parents using the Parents' Evaluation of Aural/oral performance of Children (PEACH) questionnaire. There were significant correlations among language measures, and also between the standardized language measures and the PEACH. On average, children who had language deficits exhibited difficulties in everyday functioning. The evidence lends support to a systematic use of parents' observations to evaluate communicative functioning of children in real life. On average, children's language attainment decreased as hearing loss increased, more so for children of less highly educated parents. Factors that were not significantly associated with speech and language outcomes at 3 years were age of amplification and socioeconomic status. As multiple factors affect children's outcomes, it will be possible to examine their effects on outcomes of children when all data in the LOCHI study are available.

Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin.

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 +/- 1,470 vs. 900 +/- 390%.s. The norepinephrine (NE) concentration required to increase PGE(2) and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE(2) release from 67 +/- 6 to 150 +/- 13 pg/min and substance P release from 6.7 +/- 0.8 to 12.3 +/- 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE(2) release from 64 +/- 5 to 129 +/- 22 pg/min and substance P release from 4.5 +/- 0.4 to 6.6 +/- 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE(2) and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE(2) release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.