369 research outputs found

    The Effects of Prompting on Catching Proficiency of Young Mildly Retarded Children.

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    This study sought to determine the effects of prompting on the catching proficiency of young mildly mentally retarded boys. The study randomly assigned seventy-two 7 year old boys, thirty-six nondisabled and thirty-six mildly mentally retarded, to 3 treatment groups. The treatment were No, 1 or 3 prompts. The subjects were initially given an catching proficiency pretest. Next, they were given 6 practice sessions over a 2 week period. Finally, they were given a catching proficiency posttest. Both the mentally retarded and nondisabled groups in this study improved with practice. In terms of prompting, 1 prompt was as effective as 3 prompts

    Domenico Scarlatti, artista fugidio: visĂ”es de seu “estilo misto” ao fim do sĂ©culo XVIII

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    Uma mudança permanente aos 34 anos de idade, da ItĂĄlia para os serviços privados da princesa Maria BĂĄrbara, em Portugal e posteriormente na Espanha, permitiu que Domenico Scarlatti fugisse da fama e da classificação estilĂ­stica. Na ausĂȘncia de uma categoria convincente para a mĂșsica de Scarlatti – pĂłs-Barroca? PrĂ©-ClĂĄssica? Galante? TransitĂłria? – o especialista em Scarlatti, W. Dean Sutcliffe, recorre Ă  expressĂŁo adequada “estilo misto”. Entretanto, Sutcliffe reconhece que “muito das sonatas de Scarlatti deve ser considerado Ă  luz do estilo ClĂĄssico”, e eu tambĂ©m. Particularmente, o tipo especĂ­fico de forma bipartida que o compositor emprega na maior parte de suas 555 sonatas para teclado sobreviventes dificilmente era Ășnico no continente durante o tempo em que viveu, e esta forma continuou a aparecer mesmo muito depois de dar lugar ao que hoje chamamos de “sonata ClĂĄssica”. Os “mecanismos de escape” musicais do compositor – atrasos surpreendentes de resultados esperados por meio de cadĂȘncias evadidas e repetiçÔes “mais uma vez” – podem ser “avistados” em grande parte do repertĂłrio do fim do sĂ©culo XVIII, especialmente na mĂșsica de Mozart. Todavia, nenhuma comparação da mĂșsica de Scarlatti com a de seus sucessores pode diminuir sua exuberĂąncia “espanhola”, sua predileção pela justaposição de ideias totalmente diferentes em um Ășnico movimento – resumindo, suas contribuiçÔes caracterĂ­sticas e sem paralelo para a mĂșsica para teclado. Palavras-chave: A forma sonata Tipo 2 de Hepokoski e Darcy; EstratĂ©gias cadenciais; A tĂ©cnica “mais uma vez”; Virtuosismo com sequĂȘncia

    Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

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    DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits

    The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study

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    Background: The potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear.Methods: A large population-based case-control study on breast cancer in postmenopausal women in Germany recruited 2002-2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015.Results: A first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p &lt; 0.001). Patients with a first degree family history of breast cancer were more likely to have had &gt;10 mammograms (MG) (42.7% vs. 24.9%, p &lt; 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p &lt; 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p &lt; 0.001) and a higher number of MG (&gt;= 10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p &lt; 0.001) and imaging-assisted tumor detection (HR 0.66, p &lt; 0.001) were associated with better overall survival but not with a positive family history.Discussion: Patients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history. (C) 2020 The Authors. Published by Elsevier Ltd.</p

    Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer

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    Objective: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis, we assess whether resection of the hottest node could be sufficient to detect sentinel lymph node (SLN) metastasis. Methods: Patients with primary vulvar cancer receiving an SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. Results: A total of 145 patients with SNB were analyzed;thereof, 144 underwent bilateral SNB, resulting in 289 analyzed groins. A median of 2 SLNs (range, 1-7) per groin were removed. From 94 (32.5%) of 289 groins, more than 2 SLNs were excised. Median overall SLN isotope count was 1400 cps. In 50 groins, a positive SLN was detected (unilateral in 38 patients, bilateral in 6). The median number of positive SLN per groin was 1 (range, 1-4). The SLN with the highest isotope count carried metastases in 36 (78.3%) of 46 groins (in 4 cases, the highest count was unknown). In 10 (21.7%) of 46 positive groins, the SLN with the highest count was not the metastatic SLN (9/10 second highest count). Median count of these 10 SLN was 60% of the highest count with a range from 11.0% to 74.0%. Conclusions: The highest isotope count does not reliably detect the positive SLN in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SLN accumulating relevant radioactive tracer over background activity

    Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis

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    Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. Methods: The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Discussion; Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases

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    VEGF-C expression attributes the risk for lymphatic metastases to ovarian cancer patients

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    Background: Peritoneal dissemination and retroperitoneal lymph node involvement are main routes for progression of epithelial ovarian cancer (EOC). Vascular endothelial growth factor (VEGF) mediated angiogenesis has been identified as an important mechanism promoting tumour progression. Methods: Tumour tissue of 100 patients with EOC was analysed for protein expression of vascular endothelial growth factor (VEGF)-A, -C, -D by Western Blot analysis. Expression patterns in patients with ` extensive intraperitoneal' metastases (pT3c pN1 and pT3b-pT3c pN0, n= 80) were compared to patients with ` predominantly retroperitoneal' metastases (pT1a-pT3b, pN1, n= 20). Overall and progression-free survival was analysed by Kaplan-Meier method. Results: While no significant differences in expression levels among the different modes of metastases were noted for VEGF-A and -D, VEGF-C expression was significantly higher in the group of predominantly retroperitoneal metastases compared to the group with extensive intraperitoneal metastases. Patients with high VEGF-C expression had a significantly worse overall survival compared to patients with low expression levels. Conclusions: Retroperitoneal tumour progression in EOC patients is associated with high VEGF-C expression. VEGF-C may serve as a molecular marker to identify patients with assumed high risk for lymphatic metastases, who might benefit from specific treatment strategies
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