Reading comprehension and strategy use: Comparing bilingual children to their monolingual peers and to bilingual adults.

The current study investigated the predictive ability of language knowledge and reported strategy use on reading comprehension performance in English-speaking monolingual and bilingual students. One hundred fifty-five children in grade 4 through 6 (93 bilinguals and 62 monolinguals) were assessed on receptive vocabulary, word reading fluency, reading comprehension, and reading strategy use in English. An additional 38 adult bilinguals (i.e., English Language Learners) were assessed on the same measures. Although, the bilingual adult group and bilingual children had significantly lower English vocabulary knowledge relative to the monolingual children, the bilingual adults exhibited reading comprehension performance that was on par with the monolingual children; both groups outperformed the bilingual children. This discrepancy was accounted for by reported strategy use, wherein bilingual adults reported more inferencing, more connecting between sections of text and more reference to the text structure than the children. Reported strategy use also accounted for unique variance in reading comprehension performance above and beyond the contributions of English vocabulary knowledge and word reading fluency. Findings highlight the strategies that successful readers report and emphasize the value of promoting effective strategy selection in addition to language instruction in the development of reading comprehension skill.

The interRAI Child and Youth Suite of Mental Health Assessment Instruments: An Integrated Approach to Mental Health Service Delivery.

Various biological, social, psychological, and environmental factors impact children and youth living with mental health problems across their lifespan. To meet the wide-ranging challenges of mental illness, service system integration is needed to improve efficiencies and reduce fragmentation. Unfortunately, the mental health system has been plagued by the lack of coordination across services. There is a general consensus that mental health service delivery must ensure a child or youth's needs are addressed in a collaborative, coordinated, and seamless manner. A key element to successful integration is the development of a comprehensive standardized screening and assessment system. Numerous assessments have been developed to assess child mental health and functioning, but they typically have a very narrow focus with limited use and utility. Not only does this reduce the ability to take a life course perspective to mental health, but this uncoordinated approach also results in redundancies in information collected, additional resources, and increased assessor burden for children, youth, and their families. The interRAI child and youth mental health assessment suite was developed in response to the need for an integrated mental health system for young persons. This suite includes screening and assessment instruments for in-patient and community settings, emergency departments, educational settings, and youth justice custodial facilities. The instruments form a mental health information system intentionally designed to work in an integrated fashion beginning in infancy, and incorporate key applications such as care planning, outcome measurement, resource allocation, and quality improvement. The design of these assessment tools and their psychometric properties are reviewed. Data is then presented using examples related to interpersonal trauma, illustrating the use and utility of the integrated suite, along with the various applications of these assessment systems.

Abuse, Mental State, and Health Factors Pre and during the COVID-19 Pandemic: A Comparison among Clinically Referred Adolescents in Ontario, Canada.

Throughout the COVID-19 pandemic, population surveys revealed increased levels of anxiety and depression, while findings from large-scale population data analyses have revealed mixed findings with respect to the mental health consequences for children and youth. The purpose of this study was to examine the impact of the COVID-19 pandemic on the well-being and health-compromising behaviors of adolescents (12-18 years) previously referred for mental health services. Data were collected (pre-pandemic n = 3712; pandemic n = 3197) from mental health agencies across Ontario, Canada using the interRAI Child and Youth Mental Health assessment. Our findings revealed no increased incidence of witnessing domestic violence nor experiencing physical, sexual, or emotional abuse. Further, there were no increases in the risk of self-harm and suicide, anxiety, or depression among our sample of clinically referred youth. Finally, results demonstrated no increase in problematic videogaming/internet use, disordered eating, or alcohol intoxication, and a decrease in cannabis use. Our findings add to the growing body of knowledge as to the impact of the COVID-19 pandemic on children and youth. Further, findings underscore the importance of understanding the nuanced impact of the pandemic on various subgroups of children, youth, and families and highlight the need for continued monitoring of outcomes for these children and youth.

An Examination of Correlates of Quality of Life in Children and Youth With Mental Health Issues.

Quality of life (QoL) is significantly lower in children with mental health issues compared to those who are typically developing or have physical health problems. However, little research has examined factors associated with QoL in this particularly vulnerable population. To address this limitation, 347 clinically referred children and adolescents were assessed using the interRAI Child and Youth Mental Health (ChYMH) Assessment and Self-reported Quality of Life- Child and Youth Mental Health (QoL-ChYMH). Hierarchical multiple linear regression analyses were conducted to examine QoL at the domain-specific level. Children and adolescents who experienced heightened anhedonia and depressive symptoms reported lower social QoL (e.g., family, friends and activities; p = 0.024, 0.046, respectively). Additionally, children and youth who experienced heightened depressive symptoms reported lower QoL at the individual level (e.g., autonomy, health; p = 0.000), and level of basic needs (e.g., food, safety; p = 0.013). In contrast, no mental state indicators were associated with QoL related to services (e.g., school, treatment). Due to the paucity of research examining predictors of QoL in children and youth with mental health challenges, this study contributes to the field in assisting service providers with care planning and further providing implications for practice.

Autism Spectrum Screening Checklist (ASSC): The Development of a Scale to Identify High-Risk Individuals Within the Children's Mental Health System.

Autism Spectrum Disorder (ASD) is a complex childhood onset neurodevelopmental disorder that has become the fastest growing developmental disability. Due to the increased demand for diagnostic assessments and subsequent increased wait times, standardized screening as part of regular clinical practice is needed. More specifically, there is an important need for the development of a more streamlined screening tool within an existing assessment system to identify those at greatest risk of having ASD. The current study utilized data from ~17,000 assessments obtained within the province of Ontario, based on the interRAI Child and Youth Mental Health (ChYMH) and Child and Youth Mental Health and Developmental Disability (ChYMH-DD), to develop a scale to identify children who have a higher likelihood of having autism. The scale was then tested on a trial population with data from the interRAI Early Years instrument. Further analyses examined the predictive validity of the scale. The Autism Spectrum Screening Checklist (ASSC) was found to be a good predictor of ASD with a sensitivity of 0.73 and specificity of 0.62, at the recommended cut-point of 2+. The results were consistent across several age ranges, specifically from 2 to 21 years of age. The ASSC scale provides an initial screen to help identify children and youth at heightened risk for autism within larger populations being assessed as part of routine practice. The main goal for the development and implementation of the ASSC scale is to harness the power of the existing interRAI assessment system to provide a more efficient, effective screening and referral process. This will ultimately help improve patient outcomes through needs-based care.

Risk of Injury to Others: The Development of an Algorithm to Identify Children and Youth at High-Risk of Aggressive Behaviours.

Youth violence is considered one of the most preventable causes of morbidity and premature mortality. Various risk factors have previously been identified, however, there is presently a crucial need to develop effective decision-support tools in order to identify children and youth at increased risk for violence. The current study utilised data collected from the interRAI Child and Youth Mental Health Screener (ChYMH-S), within the province of Ontario, to develop and validate a methodology for the purpose of identifying young persons who were at greater risk of harm to others. Additional data from 59 mental health agencies validated the algorithm, and it was found to be a strong predictor of harmful behaviour toward others. The RIO algorithm provides a valuable decision-support tool with strong psychometric properties that may be used to identify young persons who exhibit signs or symptoms associated with increased likelihood of harm toward others, in order to provide early intervention efforts for these vulnerable youth, thereby reducing the likelihood of future aggressive behaviours.

Risk of Suicide and Self-harm in Kids: The Development of an Algorithm to Identify High-Risk Individuals Within the Children's Mental Health System.

Suicide is the second leading cause of death in adolescents within Canada. While several risk factors have been found to be associated with increased risk, appropriate decision-support tools are needed to identify children who are at highest risk for suicide and self-harm. The aim of the present study was to develop and validate a methodology for identifying children at heightened risk for self-harm and suicide. Ontario data based on the interRAI Child and Youth Mental Health Screener (ChYMH-S) were analyzed to develop a decision-support algorithm to identify young persons at risk for suicide or self-harm. The algorithm was validated with additional data from 59 agencies and found to be a strong predictor of suicidal ideation and self-harm. The RiSsK algorithm provides a psychometrically sound decision-support tool that may be used to identify children and youth who exhibit signs and symptoms noted to increase the likelihood of suicide and self-harm.

A Case-Mix System for Children and Youth With Developmental Disabilities.

Limited funding across health and social service programs presents a challenge regarding how to best match resources to the needs of the population. There is increasing consensus that differences in individual characteristics and care needs should be reflected in variations in service costs, which has led to the development of case-mix systems. The present study sought to develop a new approach to allocate resources among children and youth with intellectual and developmental disabilities (IDD) as part of a system-wide Medicaid payment reform initiative in Arkansas. To develop the system, assessment data collected using the interRAI Child and Youth Mental Health-Developmental Disability instrument was matched to paid service claims. The sample consisted of 346 children and youth with developmental disabilities in the home setting. Using automatic interactions detection, individuals were sorted into unique, clinically relevant groups (ie, based on similar resource use) and a standardized relative measure of the cost of services provided to each group was calculated. The resulting case-mix system has 8 distinct, final groups and explains 30% of the variance in per diem costs. Our analyses indicate that this case-mix classification system could provide the foundation for a future prospective payment system that is centered around stability and equitability in the allocation of limited resources within this vulnerable population.

BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.

Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-ß (TGF-ß) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-ß signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy.

ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma.

Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, these data suggest ID1 could be a promising therapeutic target in patients with glioblastoma. SIGNIFICANCE: These findings show that the transcriptional regulator ID1 is critical for glioblastoma initiation and chemoresistance and that inhibition of ID1 enhances the effect of temozolomide, delays tumor recurrence, and prolongs survival.

A novel amplification-based approach to enable gene expression profiling from small clinical tumor specimens.

Glioblastoma is the most common and deadly type of brain cancer. Over the past decade, several divergent genetic pathways have been implicated in the initiation, progression and clinical outcome of this disease. As our understanding of GBM expands and identifies actionable targets specific to individual tumors, there will be a pressing need for the development of new tools that will maximize the use of limited clinical samples to enable the employment of personalized care paradigms. We used PrimePCR validated assays to generate a custom real-time PCR screening panel, containing 74 previously published mRNA targets showing gene expression changes in glioblastoma, and five house-keeping genes. A cohort of 19 frozen brain specimens were analyzed, including WHO Grade II oligodendroglioma (n = 3), WHO Grade II astrocytoma (n = 2), WHO Grade III astrocytoma (n = 1), and glioblastoma (n = 13). Four normal brain samples were also analyzed. We performed RNA extraction, followed by cDNA synthesis, multiplexed pre-amplification and SYBR-based qPCR, to generate expression profiles on all samples. We demonstrated that the workflow shows high tolerance to variation in RNA quality (RIN 8.5-4) and high sensitivity in detection. cDNA input that is equivalent to 3 ng of starting RNA was sufficient to conduct accurate semiquantitative analysis of the panel of 79 assays. Using principal component analysis, we were able to accurately separate glioblastoma from low-grade glioma. The two WHO Grade III tumors analyzed clustered with glioblastoma, but showed more similarity to Grade II gliomas. In this study, we have shown the feasibility of consolidating high-throughput data into a single functional panel capable of accurately classifying glioma specimens based solely on semiquantitative gene expression profiling.

Sox10 is superior to S100 in the diagnosis of meningioma.

Meningiomas are the most common primary cranial tumor arising in the central nervous system and its coverings, constituting 35.5% of primary brain tumors. Schwannomas account for 8.3% of primary neoplasms of the central nervous system. Occasionally these tumors can show overlapping morphology, most conspicuously in the fibrous variant of meningioma. In such cases, immunohistochemistry can help to establish a definitive diagnosis. Currently S100 is the most commonly used immunohistochemical stain to show neural crest differentiation in tumors. This may lead to potential misclassification of meningeal tumors, as up to 70% of fibrous meningiomas can show S100 expression. Our study sought to determine if Sox10 would prove a more specific alternative to S100 in cases of meningioma when the differential diagnosis includes schwannoma. We compared the mRNA expression of S100B and Sox10 using the publicly available GSE16581 meningioma dataset. We then studied Sox10 and S100 protein expression using immunohistochemistry in 147 cases of meningioma using tissue microarrays (TMA) and 19 cases of fibrous meningioma using full cross-sections (FCS). Sox10 and S100B mRNA expression in GSE16581 showed no significant correlation in meningothelial tumors (r=-0.002, P=0.989). By immunohistochemistry, S100 was positive in 14/19 (73.7%) of FCSs and 71/147 (48.3%) of TMA tumors, whereas Sox10 (protein name) was positive in only 1/19 (5.3%) of FCSs and 3/147 (2.0%) of TMA tumors. In summary, Sox10 is superior to S100 in the differential diagnosis of schwannoma and meningioma.