Genetic alterations in gliosarcoma and giant cell glioblastoma

The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas. This article is protected by copyright. All rights reserved

The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism

Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. What's new? Cancer cells avoid senescence in part by reactivating telomerase (TERT), a ribonucleoprotein that replenishes shortening telomeres. Here, the authors discover a positive association between TERT promoter mutations and unfavorable prognosis in glioblastoma patients from Portuguese and Brazilian origin. This association was only observed in patients with a specific allelic background (AA) in a TERT polymorphism (rs2853669) recently linked to enhanced TERT mRNA levels. The authors recommend considering the allelic status of rs2853669 when assessing the prognostic value of TERT promoter mutations in glioblastoma patients.Portuguese Fundação para a Ciência e Tecnologia and Fundo Europeu de Desenvolvimento Regional (FEDER) and COMPETE – Programa Operacional Factores de Competitividade (POFC); Grant number: PTDC/SAU-ONC/115513/2009; Grant sponsor: Brazilian FAPESP; Grant number: 2012/19590–0; Grant sponsor: Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under Quadro de Referência Estrategico Nacional (QREN) through Fundo Europeu de Desenvolvimento Regional (FEDER); Grant number: Microenvironment, Metabolism and Cancer; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: SFRH/BD/81940/2011; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: Program Ciência 2007; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: Program Ciência 2008; Grant sponsor: Brazilian FAPESP; Grant number: 2013/25787-3; Grant sponsor: NORTE2020; Grant number: NORTE-01-0145-FEDER-000029Fundação para a Ciência e Tecnologiainfo:eu-repo/semantics/publishedVersio

Assessing motivation in mandatory continuing education

Due to the public demand for accountability for quality within health care systems, the National Council for Therapeutic Recreation Certification and California Board of Recreation and Park Certification have, within the past decade, instituted mandatory continuing education for professional recertification within the therapeutic recreation (TR) profession. These changes brought an end to voluntary continuing education within the TR profession. The literature supports the notion that intrinsically motivated learning opportunities are a more effective learning experience than extrinsically motivated learning opportunities (Rockhill, 1981). Intrinsic motivation is defined as the act of performing an activity in the absence of any reward whereas extrinsic motivation is performing an activity for a reward (Deci & Ryan, 1985). A question to pose is: does requiring continuing education for recertification significantly decrease intrinsic motivation and affect learning? This exploratory study tested the hypothesis that TR professionals within California, as a group, are primarily motivated by intrinsic factors to participate in continuing education programs in preparation for recertification. In order to test the hypothesis an instrument was developed. The instrument tested the hypothesis by answering the following research questions: (a) what are the motivational factors that influence TR professionals' participation in continuing professional education programs, (b) does requiring continuing education for recertification influence the decision-making process of TR professionals participating in continuing professional education programs, and (c) what are the TR professionals' attitudes toward mandatory continuing education? The instrument was developed incorporating survey questions with intrinsic and extrinsic orientations. A panel of experts reviewed the instrument and it was field tested with a selected group of TR professionals. The targeted population was obtained from the current lists of three TR organizations. The study population of 377 \Vas randomly selected from a population of 764. An initial mailing with a self-addressed return envelope and a follow-up mailing were sent out and 162 (42.97%) useable surveys were returned. The data was collected and analyzed by using the Statistical Package for the Social Sciences (SPSS) program. The frequencies of all responses to the questions on the survey were recorded. The data supported the literature and the hypothesis of this study. TR professionals in California indicated that they were primarily motivated to participate in continuing professional education programs based on self-growth needs, i.e. intrinsic value. One of the findings revealed that complying with mandatory continuing education was a salient factor in the decision-making process of TR professionals in California, but was not the primary motivation for participation in continuing education programs. This was consistent with other research in other health care professions (O'Connor, 1982; Thomas, 1986; Urbano, Jahns, & Urbano, 1988). The study revealed that although TR professionals in California meet the requirements of participating in continuing education programs in preparation for recertification, they choose and participate in continuing education based on developing professional skills and knowledge in order to improve their professional services.California State University, Northridge. Department of Leisure Studies and Recreation.Includes bibliographical references (leaves 60-64

Anti-stokes cooling in semiconductor nanocrystal quantum dots: a feasibility study

In this review, we discuss the feasibility of laser cooling of semiconductor nanocrystal quantum dots by phonon-assisted anti-Stokes photoluminescence. Taking into account recent experimental advances, in particular, the development of semiconductor nanocrystals with very high quantum yield, we analyze in detail how the various physical processes in nanocrystals might help or hinder the cooling process. Possible experimental approaches to achieve efficient optical cooling are also discussed.Science Foundation Ireland - 02/IN.1/I47; 00/PI.1/C077A.2; 07/IN.1/B186

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis

Laboratory-based X-ray phase-imaging scanner using Talbot-Lau interferometer for non-destructive testing

An X-ray Talbot-Lau interferometer scanning setup consisting of three transmission gratings, a laboratory-based X-ray source that emits X-rays vertically, and an image detector on the top has been developed for the application of X-ray phase imaging to moving objects that cannot be tested clearly with conventional absorption contrast. The grating-based X-ray phase imaging method usually employs a phase-stepping (or fringe-scanning) technique by displacing one of the gratings step-by-step while the object stays still. Since this approach is not compatible with a scanner-type application for moving objects, we have developed a new algorithm for achieving the function of phase-stepping without grating displacement. By analyzing the movie of the moiré pattern as the object moves across the field of view, we obtain the absorption, differential phase, and visibility images. The feasibility of the X-ray phase imaging scanner has been successfully demonstrated for a long sample moving at 5 mm/s. This achievement is a breakthrough for the practical industrial application of X-ray phase imaging for screening objects carried on belt-conveyers such as those in factories

Empirical Calculation Method of Bypass Leakage in Scroll Compressors

This study presents an empirical method to calculate the bypass leakage mass flow rate along the tip seal in a scroll compressor. The leakage flows through small axial and radial clearances between the orbiting and fixed scrolls of scroll compressor were previously studied by Ishii et al. In these earlier studies, the pressure decay in the pressurized vessel due to leakage through the axial and radial clearances was measured using a maximum pressure of 3 MPa for CO2 and 0.6 MPa for R22. The Darcy-Weisbach equation for incompressible, viscous fluid flow through the thin rectangular cross-section was applied to calculate the leakage mass flow rate that matched the pressure decay characteristics. The empirical friction factors were determined and plotted on a Moody diagram. As a result, the empirical friction factors for both axial and radial clearance leakage flows have been determined and shown to take on essentially the same value for both CO2 and R22, despite the significantly different working pressures. In contrast, the flow patterns in bypass leakage along the tip seal are so complicated that not even the leakage characteristics are known definitively. No method exists for calculating the bypass leakage mass flow rate. In the present study, a bypass leakage model was constructed, compatible with a production-type scroll compressor with a large cooling capacity. A similar test of the pressure decay in the pressurized vessel due to bypass leakages were conducted with the refrigerant gas R410A. The measured pressure decay characteristics were then simulated by the Darcy-Weisbach equation with the empirical friction factors from our previous study for the leakage flow through the axial clearance. In the present simulations of the measured pressure decay, the complicated flow patterns through bypass clearances were classified into two representative rectangular thin cross-section leakage passes, one with an equivalent width and the other with an equivalent length. Empirical friction factor values for the equivalent pass width and length were determined to match the measured pressure decays. As a result, the calculation of the bypass leakage flow rate along the tip seal in scroll compressors can be accomplished using a simple scheme in terms of the equivalent pass width and equivalent pass length for two representative leakage passes forming a thin rectangular cross-section and applying empirically determined friction factors,

Lubrication Tests to Support Optimal Performance Design Guidelines for Thrust Slide-Bearings in Scroll Compressors

This study focuses on the role of lubrication in the optimal performance design guidelines for the thrust slide-bearings in scroll compressors. The theoretical analysis of Ishii et al. showed that the minimum friction power loss in the thrust slide-bearing occurs at a certain outer radius of the friction surface. In the theoretical development, the physical thrust slide-bearing was modeled as a cylindrical thrust plate, representing the orbiting scroll, and the flat plate, representing the fixed scroll, with the same friction area as the physical bearing. The outer radius of the friction surface was varied for a fixed inner radius, where the fluid wedge angle between the sliding surfaces, due to axial loading on the thrust plate, was assumed to be constant at a small value. The average Reynolds equation by Patier & Cheng and the solid contact theory by Greenwood & Williamson were applied to calculate the resultant lubrication performance and finally the friction power loss at the sliding surface. The model showed that the friction power loss drastically decreases and then gradually increases, with increasing outer radius of the sliding surface.  The minimum value of friction power loss was about 80% lower than that of the conventional design thrust slide-bering. In order to confirm experimentally this predicted optimal lubrication performance, a thrust slide-bearing cylindrical-model submerged in a refrigerant oil SUNISO-RB68A was operated under pressurized conditions using R410A as the pressurizing gas. The pressure difference across the friction surface of the thrust bearing was fixed at 0.6 MPa, corresponding to the rated operation condition of a small cooling capacity scroll compressor. In the experiments, a special device was fabricated to maintain a constant fluid wedge angle between the friction surfaces due to the net pressure-induced elastic deformation of the thrust plate. The friction power loss at the friction surface was measured over a wide range of orbiting speeds from 1200 rpm up to 6000 rpm for a fixed orbiting radius of 3.0 mm. The resulting measured data exhibited showed the predicted tendency that the lubrication of the thrust slide-bearing is substabtially by increasing the outer radius. The friction power loss decreased with increasing outer-to-inner radii ratio of friction surface. The minimum loss occurred at an outer-to-inner radii ratio of about 2.1 for an operating speed of 3600 rpm, a significant 80% reduction relative to the usual conventional design ratio