Full-Day Kindergarten in California: Lessons From Los Angeles

Analyzes the impact of full-day kindergarten on academic, grade retention, and English fluency outcomes through second grade by school and student characteristics, with a focus on the economically disadvantaged and English learners. Outlines implications

Advanced Glycation End-Products Suppress Mitochondrial Function and Proliferative Capacity of Achilles Tendon-Derived Fibroblasts

Debilitating cases of tendon pain and degeneration affect the majority of diabetic individuals. The high rate of tendon degeneration persists even when glucose levels are well controlled, suggesting that other mechanisms may drive tendon degeneration in diabetic patients. The purpose of this study was to investigate the impact of advanced glycation end-products on tendon fibroblasts to further our mechanistic understanding of the development and progression of diabetic tendinopathy. We proposed that advanced glycation end-products would induce limitations to mitochondrial function and proliferative capacity in tendon-derived fibroblasts, restricting their ability to maintain biosynthesis of tendon extracellular matrix. Using an in-vitro cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived advanced glycation end-products (0, 50, 100, and 200 μg/ml) for 48 hours in normal glucose (5.5 mM) and high glucose (25 mM) conditions. We demonstrate that tendon fibroblasts treated with advanced glycation end-products display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with extracellular matrix remodeling, mitochondrial energy metabolism, and apoptosis. Our findings suggest that advanced glycation end-products disrupt tendon fibroblast homeostasis and may be involved in the development and progression of diabetic tendinopathy

Implementação estadual do edTPA em preparação para testes de alto risco: Um estudo de métodos mistos das preocupações dos coordenadores do edTPA

This study examined the implementation of high-stakes adoption of edTPA® in one state in the year prior to consequential use of edTPA scores for teacher licensure. Using a mixed methods design, we investigated concerns of coordinators who were responsible for edTPA implementation in their institutions. We utilized the Concerns Based Adoption Model (CBAM) to understand edTPA coordinators’ Stages of Concern, the nature of the challenges they faced, and the professional development opportunities that alleviated their concerns. Based on the CBAM survey, the most common Stage of Concernfor edTPA coordinators was Management.Coordinators’ interviews revealed the nature of their concerns at different stages and how the size of their institution and supportive resources at particular times may have played a crucial role in shaping the edTPA roll-out in their institutions. The use of the CBAM framework enabled edTPA coordinators (a) to understand their own concerns about the high-stakes policy, (b) to articulate the complexities involved in implementing edTPA initiatives, and (c) to underscore the importance of relating concerns to appropriate professional development opportunities and support for themselves as well as their faculty. Este estudio examinó la implementación de la adopción de edTPA® de alto riesgo en un estado previo al uso consecuente de los puntajes de edTPA para la licencia de maestros. Usando un diseño de método mixto, investigamos las preocupaciones de los coordinadores responsables de implementar edTPA en sus instituciones. Utilizamos el Modelo de adopción basado en la preocupación (CBAM) para comprender las etapas de preocupación para los coordinadores de edTPA, la naturaleza de los desafíos que enfrentaron y las oportunidades de desarrollo profesional que alivian sus preocupaciones. Según la investigación de CBAM, la etapa de preocupación más común para los coordinadores de edTPA fue la gestión. Las entrevistas con los coordinadores revelaron la naturaleza de sus preocupaciones en diferentes etapas y cómo el tamaño de su institución y los recursos de apoyo en ciertos momentos pueden haber jugado un papel crucial en la definición de la implementación de edTPA en sus instituciones. El uso del marco CBAM ha permitido a los coordinadores de edTPA (a) comprender sus propias preocupaciones sobre la política de alto riesgo, (b) articular las complejidades involucradas en la implementación de iniciativas de edTPA, y (c) subrayar la importancia de relacionar las preocupaciones con oportunidades apropiadas para el desarrollo profesional y el apoyo para ellos mismos y la facultad.Este estudo examinou a implementação da adoção de edTPA® de alto risco em um estado do ano anterior ao uso consequente das pontuações de edTPA para licenciamento de professores. Usando um design de métodos mistos, investigamos as preocupações dos coordenadores responsáveis pela implementação do edTPA em suas instituições. Utilizamos o Modelo de Adoção com Base em Preocupações (CBAM) para entender os Estágios de Preocupação dos coordenadores da edTPA, a natureza dos desafios que enfrentaram e as oportunidades de desenvolvimento profissional que atenuaram suas preocupações. Com base na pesquisa da CBAM, o estágio de preocupação mais comum para os coordenadores da edTPA foi o gerenciamento. As entrevistas dos coordenadores revelaram a natureza de suas preocupações em diferentes estágios e como o tamanho de sua instituição e os recursos de suporte em determinados momentos podem ter desempenhado um papel crucial na definição da implementação do edTPA em suas instituições. O uso da estrutura CBAM permitiu aos coordenadores da edTPA (a) entender suas próprias preocupações sobre a política de altos riscos, (b) articular as complexidades envolvidas na implementação de iniciativas da edTPA, e (c) sublinhar a importância de relacionar as preocupações às oportunidades apropriadas de desenvolvimento profissional e apoiar a si e ao corpo docente

Complexity and Information: Measuring Emergence, Self-organization, and Homeostasis at Multiple Scales

Concepts used in the scientific study of complex systems have become so widespread that their use and abuse has led to ambiguity and confusion in their meaning. In this paper we use information theory to provide abstract and concise measures of complexity, emergence, self-organization, and homeostasis. The purpose is to clarify the meaning of these concepts with the aid of the proposed formal measures. In a simplified version of the measures (focusing on the information produced by a system), emergence becomes the opposite of self-organization, while complexity represents their balance. Homeostasis can be seen as a measure of the stability of the system. We use computational experiments on random Boolean networks and elementary cellular automata to illustrate our measures at multiple scales.Comment: 42 pages, 11 figures, 2 table

Valganciclovir for suppression of human herpesvirus-8 replication: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Human herpesvirus-8 (HHV-8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV-8 replication, but no randomized clinical trials have been conducted. METHODS: A total of 26 men infected with HHV-8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2-week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV-8 and CMV DNA were quantified by real-time PCR. RESULTS: A total of 16 human immunodeficiency virus (HIV)-positive men and 10 HIV-negative men enrolled in and completed the study. Of the 3,439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV-8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33-0.90]; P = .02). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08-0.48]; P < .001). Shedding of HHV-8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea. CONCLUSIONS: Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV-8 replication

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Glucocorticoid Receptor 1B and 1C mRNA Transcript Alterations in Schizophrenia and Bipolar Disorder, and Their Possible Regulation by GR Gene Variants

Abnormal patterns of HPA axis activation, under basal conditions and in response to stress, are found in individuals with schizophrenia and bipolar disorder. Altered glucocorticoid receptor (GR) mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC) in psychiatric illness have also been reported, but the cause of these abnormalities is not known. We quantified expression of GR mRNA transcript variants which employ different 5′ promoters, in 35 schizophrenia cases, 31 bipolar disorder cases and 34 controls. We also explored whether sequence variation within the NR3C1 (GR) gene is related to GR mRNA variant expression. Total GR mRNA was decreased in the DLPFC in schizophrenia cases relative to controls (15.1%, p<0.0005) and also relative to bipolar disorder cases (8.9%, p<0.05). GR-1B mRNA was decreased in schizophrenia cases relative to controls (20.2%, p<0.05), while GR-1C mRNA was decreased in both schizophrenia and bipolar disorder cases relative to controls (16.1% and 17.2% respectively, both p<0.005). A dose-dependent effect of rs10052957 genotype on GR-1B mRNA expression was observed, where CC homozygotes displayed 18.4% lower expression than TC heterozygotes (p<0.05), and 31.8% lower expression than TT homozygotes (p<0.005). Similarly, a relationship between rs6190 (R23K) genotype and GR-1C expression was seen, with 24.8% lower expression in GG homozygotes than GA heterozygotes (p<0.01). We also observed an effect of rs41423247 (Bcl1) SNP on expression of 67 kDa GRα isoform, the most abundant GRα isoform in the DLPFC. These findings suggest possible roles for the GR-1B and GR-1C promoter regions in mediating GR gene expression changes in psychotic illness, and highlight the potential importance of sequence variation within the NR3C1 gene in modulating GR mRNA expression in the DLPFC

Post hoc Analysis for Detecting Individual Rare Variant Risk Associations Using Probit Regression Bayesian Variable Selection Methods in Case-Control Sequencing Studies

Rare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single-marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden-type approaches attempt to identify aggregation of RVs across case-control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large-scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway-level RV analysis results from a prostate cancer (PC) risk case-control sequencing study. Finally, we discuss potential extensions and future directions of this work

Skunk River Review Fall 1997, Vol 9

https://openspace.dmacc.edu/skunkriver/1018/thumbnail.jp