42 research outputs found

    Small group interventions for children aged 5-9 years old with mathematical learning difficulties

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    The research related to educational interventions for children with mathematical learning difficulties has been increasing steadily. In this chapter I focus on small group interventions for children aged 5–9 years old with learning difficulties in mathematics. First, I describe the important issues: (1) who are the children having problems in mathematics, (2) what do we mean with (special) education intervention, (3) what does Responsiveness to Intervention mean, and (4) what intervention features have been found effective for children aged 5–9 years with learning difficulties in mathematics. Then, I describe the research and developmental work that has been done in Finland on designing web services which provide evidence-based information and materials for educators. The two web services are LukiMat and ThinkMath. Together, these two web services include the knowledge base, assessment batteries and intervention tools to be used in relation to mathematical learning difficulties in the age group 5–9 years.Peer reviewe

    MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma

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    BACKGROUND: Through negative regulation of gene expression, microRNAs (miRNAs) can function in cancers as oncosuppressors, and they can show altered expression in various tumor types. Here we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many cell-fate-determining stages. MBs occur bimodally, with the peak incidence seen between 3-4 years and 8-9 years of age, although it can also occur in adults. Notch regulates a subset of the MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulated these phenomena, and can be used in anti-cancer therapies. METHODOLOGY/PRINCIPAL FINDINGS: In a screening of MB cell lines, the miRNA miR-199b-5p was seen to be a regulator of the Notch pathway through its targeting of the transcription factor HES1. Down-regulation of HES1 expression by miR-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of MB cells. MiR-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of MB cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the MB stem-cell-like (CD133+) subpopulation of cells. In our analysis of 61 patients with MB, the expression of miR-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases (P = 0.001). Correlation with survival for these patients with high levels of miR-199b expression showed a positive trend to better overall survival than for the low-expressing patients. These data showing the down-regulation of miR-199b-5p in metastatic MBs suggest a potential silencing mechanism through epigenetic or genetic alterations. Upon induction of de-methylation using 5-aza-deoxycytidine, lower miR-199b-5p expression was seen in a panel of MB cell lines, supported an epigenetic mechanism of regulation. Furthermore, two cell lines (Med8a and UW228) showed significant up-regulation of miR-199b-5p upon treatment. Infection with MB cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying miR-199b-5p indicate a clinical benefit through this negative influence of miR-199b-5p on tumor growth and on the subset of MB stem-cell-like cells, providing further proof of concept. CONCLUSIONS/SIGNIFICANCE: Despite advances in our understanding of the pathogenesis of MB, one-third of these patients remain incurable and current treatments can significantly damage long-term survivors. Here we show that miR-199b-5p expression correlates with metastasis spread, identifying a new molecular marker for a poor-risk class in patients with MB. We further show that in a xenograft model, MB tumor burden can be reduced, indicating the use of miR199b-5p as an adjuvant therapy after surgery, in combination with radiation and chemotherapy, for the improvement of anti-cancer MB therapies and patient quality of life. To date, this is the first report that expression of a miRNA can deplete the tumor stem cells, indicating an interesting therapeutic approach for the targeting of these cells in brain tumors

    Subcortical volumetric abnormalities in bipolar disorder.

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    Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227

    Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential

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    MĂŁes de crianças com deficiĂȘncia visual: dificuldades e facilidades enfrentadas no cuidado

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    Objetivou-se conhecer as dificuldades e facilidades enfrentadas pelas mĂŁes de crianças com deficiĂȘncia visual (DV) no cuidado. Trata-se de uma pesquisa qualitativa, descritiva, realizada no segundo semestre de 2011, com dez mĂŁes de crianças com deficiĂȘncia visual, de um Centro de Educação para deficientes visuais, no sul do Brasil. Foram realizadasentrevistas semiestruturadas e anĂĄlise de conteĂșdo temĂĄtica das informaçÔes. Foram verificados como dificuldades o desconhecimento acerca da doença e da forma de cuidar da criança, a falta de acesso aos serviços de saĂșde, a sobrecarga pela dependĂȘncia da criança, a falta de apoio e o preconceito na prĂłpria famĂ­lia. Quanto Ă s facilidades, foram referidos a vontade do desenvolvimento saudĂĄvel das crianças, a convivĂȘncia com profissionais qualificados para sua educação e o contato com outras crianças com DV. Faz-se importante a instrumentalização da famĂ­lia para o cuidado Ă  criança com DV como forma de garantir a aquisição de habilidades e competĂȘncias, possibilitando-a um viver com qualidade

    Self-Monitoring During Spelling Practice: Effects on Spelling Accuracy and On-Task Behavior of Three Students Diagnosed With Attention Deficit Hyperactivity Disorder

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    We used a multiple baseline across subjects design to investigate the effects of self-monitoring on the on-task behavior and spelling accuracy of three fifth-grade students diagnosed with attention deficit hyperactivity disorder (ADHD) during an independent spelling practice period in the general education environment. We also compared their on-task levels to that of peers without disabilities in the same classroom context before and after the self-monitoring intervention. Our results showed that time on-task and spelling accuracy increased for the students diagnosed with ADHD during independent spelling practice after the teacher taught them how to self-monitor. These same students' on-task behavior also increased to levels comparable to that of their peers. Suggestions for educators interested in teaching their students self-monitoring strategies are included following a discussion of the results of the analysis
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