22 research outputs found
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Information and Communication Technologies (ICT): Components, Dimensions, and its Correlates
Information and Communication Technologies (ICT) has been identified as one of the crucial factors that affect teaching effectiveness and student learning worldwide. UNESCO, many international organizations, and many governments emphasized the importance of ICT and try to incorporate ICT into education systems. This study examined self-assessed computer competency in thirteen ICT areas from two samples, e.g., the United States and Mexico. Reliability tests were conducted, and rank analysis was done among them. By using factor analysis, these thirteen areas were grouped into three categories: “basic ICT skills”; “advanced ICT skills;” and “multimedia skills and attitudes towards ICT”. Subjects showed the highest scores in basic ICT skills, which include knowledge of computer systems, use of the operating system, search internet and communication and networking. The multimedia skills and attitudes towards ICT demonstrated the second highest scores. Advanced ICT skills that include image processing, use of database, technological platforms, and web 2.0 tools was found to have the lowest competency scores among subjects. Multivariate analysis was also conducted and found that age and gender are two significant factors to predict ICT competency, and age was found to have a non-linear relationship on advanced ICT skills
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P53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, Pten and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1–3. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and Pten mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected Pten mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential
Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.
We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, TÂ cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood [1, 2]. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer.National Institutes of Health (U.S.)National Cancer Institute (U.S.)Smith Family FoundationDamon Runyon Cancer Research FoundationBurroughs Wellcome Fun
Perceptions of effective teaching
The purpose of this study was to examine the perceptions of administrators and teachers in grades 9 through 12 in Putnam County, Tennessee, regarding effective teaching. This study was conducted using the survey data from secondary school teachers and administrators. There were 12 administrators and 219 teachers who participated in this study. Two data-gathering instruments were used in this study: (a) the Ligon Effective Teaching Survey (LETS), a survey developed by the researcher; and (b) the Tuckman Teacher Feedback Form. Demographic data were collected regarding gender, number of years teaching experience, department, school, and educational level. The study examined and tested six null hypotheses for statistical significance at the .05 level. The data obtained from the participants were analyzed and executed in narrative and chart from in terms of means, standard deviations, and probabilities. To further analyze the data, t-tests were used to compare differences in teachers\u27 and administrators\u27 perceptions and differences between males and females. An F-ratio was used in comparing differences in teachers\u27 perceptions among number of years teaching experience, among departments, among educational levels, and among different schools. The following conclusions were formulated based on the results of the statistical analyses of data: (a) the majority of teachers and administrators in Putnam County, Tennessee, are male; (b) the group of teachers with 6 to 10 years teaching experience provided the smallest group of participants; (c) the group of teachers with 11 to 15 years and 16 or more years teaching experience provided the largest groups of participants; (d) teachers with masters degrees provided the largest education level group; (e) the smallest group based on department were vocational education, special education, and foreign language; (f) the largest group of participants based on department were from English; and (g) teachers tended to rate variables higher than administrators
Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma
Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M - including H3.2K27M - mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships
Recursive Partitioning Analysis of Prognostic Variables in Newly Diagnosed Anaplastic Oligodendroglial Tumors
Background: Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision making or to combine them for prognostication. Methods. We compiled a retrospective database of 1013 patients with newly diagnosed anaplastic oligodendrogliomas or oligoastrocytomas and performed a recursive partitioning analysis to generate independent prognostic classes among 587 patients with informative 1p19q status. Variables included for survival classification were age (continuous), history of prior low-grade glioma, 1p19q deletion status, histology (presence or absence of an astrocytic component), tumor lobe, tumor hemisphere, gender, extent of resection, postresection treatment, and performance status at diagnosis. Results. Recursive partitioning analysis identified 5 prognostic groups based on hazard similarity: class I (age, 60 y, 1p19q codeleted), class II (age\u3c43 y, not codeleted), class III (age 43-59 y, not codeleted, frontal lobe tumor or age ‰¥60 y, codeleted), class IV (age 43-59 y, not codeleted, not frontal lobe tumor or age 60-69 y, not codeleted), and class V (age ‰¥70 y, not codeleted). Survival differenceswere highly significant (P\u3c.0001), with medians ranging from 9.3 years (95% CI: 8.4-16.0) for class I to 0.6 years (95% CI: 0.5-0.9) for class V. Conclusions. These 5 distinct classification groups were defined using prognostic factors typically obtained during routine management of patients with anaplastic oligodendroglial tumors. Validation in a prospective clinical trial may better differentiate patients with respect to treatment outcome
Initial Treatment Patterns Over Time for Anaplastic Oligodendroglial Tumors
Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach to treatment. We sought to determine patterns of treatment delivered over time and identify clinical correlates of specific strategies using an international retrospective cohort of 1013 patients diagnosed from 19812007. Prior to 1990, most patients received radiotherapy (RT) alone as initial postoperative treatment. After 1990, approximately 50 of patients received both RT and chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone became significantly less common (67 in 19801984 vs 5 in 20052007, P \u3c .0001). CT alone was more frequently administered in later years (0 in 19801984 vs 38 in 20052007; P \u3c .0001), especially in patients with 1p19q codeleted tumors (57 of codeleted vs 4 with no deletion in 20052007; P \u3c .0001). Temozolomide replaced the combination of procarbazine, lomustine, and vincristine (PCV) among patients who received CT alone or with RT (87 vs 2 in 20052007). In the most recent time period, patients with 1p19q codeleted tumors were significantly more likely to receive CT alone (with temozolomide), whereas RT with temozolomide was a significantly more common treatment strategy than either CT or RT alone in cases with no deletion (P \u3c .0001). In a multivariate polytomous logistic regression model, the following were significantly associated with type of treatment delivered: date (5-year interval) of diagnosis (P \u3c .0001), 1p19q codeletion (P \u3c .0001), pure anaplastic oligodendroglioma histology (P \u3c .01), and frontal lobe predominance (P \u3c .05). Limited level 1 evidence is currently available to guide treatment decisions, and ongoing phase III trials will be critical to understanding the optimal therapy
HG-76SPATIAL AND TEMPORAL HOMOGENEITY OF DRIVER MUTATIONS IN DIFFUSE INTRINSIC PONTINE GLIOMA
Pediatric low-grade gliomas: Implications of the biologic era
For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifcations and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classifcation and is increasingly critical for appropriate management. Moleculartargeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown