Sample records for glioma initial experience

  1. {sup 18}F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

    Ledezma, Carlos J. [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Chen, Wei [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Sai, Victor [School of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Freitas, Bonnie [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Cloughesy, Tim [Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Czernin, Johannes [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:; Pope, Whitney [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail:


    Background and purpose: {sup 18}F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [{sup 18}F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether {sup 18}F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent {sup 18}F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had {sup 18}F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused {sup 18}F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of {sup 18}F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, {sup 18}F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and {sup 18}F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. {sup 18}F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, {sup 18}F-FDOPA activity preceded tumor detection on MRI. Conclusion: {sup 18}F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, {sup 18}F-FDOPA activity may identify tumor not visible on MRI.

  2. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)


    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  3. Glioma-initiating cells and molecular pathology: implications for therapy.

    Natsume, Atsushi; Kinjo, Sayano; Yuki, Kanako; Kato, Takenori; Ohno, Masasuke; Motomura, Kazuya; Iwami, Kenichiro; Wakabayashi, Toshihiko


    There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

  4. Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.

    Chen, Tunan; Yi, Liang; Li, Fei; Hu, Rong; Hu, Shengli; Yin, Yi; Lan, Chuan; Li, Zhao; Fu, Chuhua; Cao, Liu; Chen, Zhi; Xian, Jishu; Feng, Hua


    Glioma‑initiating cells are a small population of cells that have the ability to undergo self‑renewal and initiate tumorigenesis. In the present study, the potential role of salinomycin, a polyether antibiotic, on the suppression of glioma cell growth was investigated. GL261 glioma cells were maintained in a stem‑cell‑like status [GL261 neurospheres (GL261‑NS)] or induced for differentiation [GL261 adherent cells (GL261‑AC)]. It was demonstrated that salinomycin significantly reduced the cell viability of GL261‑NS and GL261‑AC cells in a dose‑dependent manner, with a more substantial inhibition of GL261‑NS proliferation (Psalinomycin on cell growth was more effective than that of 1‑(4‑amino‑2‑methyl‑5‑pyrimid l)‑methyl‑3‑(2‑chloroethyl)‑3‑nitrosourea hydrochloride and vincristine (PSalinomycin depleted GL261‑NS from tumorspheres and induced cell apoptosis. In addition, salinomycin prolonged the median survival time of glioma‑bearing mice (Psalinomycin may preferentially inhibit glioma‑initiated cell growth by inducing apoptosis, suggesting that salinomycin may provide a valuable therapeutic strategy for the treatment of malignant glioma.

  5. Optic radiation fiber tractography in glioma patients based on high angular resolution diffusion imaging with compressed sensing compared with diffusion tensor imaging - initial experience.

    Daniela Kuhnt

    Full Text Available OBJECTIVE: Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI. However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine. METHODS: Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR, underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS. RESULTS: HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract. CONCLUSIONS: Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.

  6. Gliomas

    Berger, M.; Weller, M.


    Key Features •Synthesizes widely dispersed information on the management of gliomas into one comprehensive resource •Chapters written by international authors who are preeminent researchers in the field •Fully explores the therapeutic options for patient care, from chemotherapy to radiotherapy to personalized approaches Description Researchers’ knowledge of gliomas continues to advance rapidly at both the basic and translational levels, and Gliomas provides a thorough overview ...

  7. Radiochemotherapy of malignant glioma in adults. Clinical experiences

    Kortmann, R.D.; Jeremic, B.; Plasswilm, L.; Bamberg, M. [Dept. for Radiation Oncology, Univ. of Tuebingen (Germany); Weller, M. [Dept. of Neurology, Univ. of Tuebingen (Germany)


    Background: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. Material and Methods: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. Results: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. Conclusions: Therefore, search for newer and more effective drugs continues, as well as for ''optimal'' administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation. (orig.)

  8. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing

    Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy de Silly, Romain; Boehler, Margaux; Calvo Tardón, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen Yonca; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul R.


    Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. PMID:27579489

  9. 12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas

    Schueller, P.; Micke, O.; Moustakis, C.; Bruns, F.; Schuck, A.; Willich, N. [University Hospital Muenster (Germany). Dept. of Radiotherapy and Radiation Oncology; Palkovic, S.; Schroeder, J.; Wassmann, H. [University Hospital Muenster (Germany). Dept. of Neurosurgery


    Background: Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. Patients and methods: From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). Results: The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomass III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p=0.0296). Total versus subtotal resection had no significant influence on survival (p=0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). Conclusion: IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT. (orig.)

  10. Initial Cooling Experiment (ICE)

    Photographic Service


    In 1977, in a record-time of 9 months, the magnets of the g-2 experiment were modified and used to build a proton/antiproton storage ring: the "Initial Cooling Experiment" (ICE). It served for the verification of the cooling methods to be used for the "Antiproton Project". Stochastic cooling was proven the same year, electron cooling followed later. Also, with ICE the experimental lower limit for the antiproton lifetime was raised by 9 orders of magnitude: from 2 microseconds to 32 hours. For its previous life as g-2 storage ring, see 7405430. More on ICE: 7711282, 7809081, 7908242.

  11. Interleukin-13 conjugated quantum dots for identification of glioma initiating cells and their extracellular vesicles.

    Madhankumar, A B; Mrowczynski, Oliver D; Patel, Suhag R; Weston, Cody L; Zacharia, Brad E; Glantz, Michael J; Siedlecki, Christopher A; Xu, Li-Chong; Connor, James R


    Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study. The exosomes were isolated from the GSC conditioned medium and the expression of IL13Rα2 in the GSC and exosomes was verified. The binding property of IL13QD to the tumor associated exosomes was initially confirmed by transmission electron microscopy. The force of attraction between the quantum dots and U251 glioma cells and the exosomes was investigated by atomic force microscopy, which indicated a higher force of binding interaction between the IL13QD and IL13Rα2 expressing glioma cells and exosomes secreted by glioma stem cells. Flow cytometry of the IL13QD and exosomes from the culture media and cerebrospinal fluid (CSF) of patients with glioma tumors indicated a distinctly populated complex pattern different from that of non-targeted quantum dots and bovine serum albumin (BSA) conjugated quantum dots confirming specific binding potential of the IL13QD to the tumor associated exosomes. The results of this study demonstrate that IL13QD can serve as an ex vivo marker for glioma stem cells and exosomes that can inform diagnosis and prognosis of patients harboring malignant disease. Functionalized quantum dots are flexible semiconductor nanomaterials which have an immense application in biomedical research. In particular, when they are functionalized with biomolecules like proteins or antibodies, they have the specialized ability to detect the expression of receptors and antigens in

  12. Radio-induced gliomas: 20-year experience and critical review of the pathology.

    Salvati, Maurizio; D'Elia, Alessandro; Melone, Graziella Angelina; Brogna, Christian; Frati, Alessandro; Raco, Antonino; Delfini, Roberto


    The authors report their personal experience with a surgical series of 16 cases of cerebral radiation-induced gliomas, defining diagnostic criteria and surgical and clinical characteristics. There were ten males and six females, with a median age of 45.9 years. Irradiation had initially been given for acute lymphoblastic leukemia (ALL) in six cases, tinea capitis in four cases, scalp hemangioma in three cases, cutaneous hemangioma, cavernous angioma, and medulloblastoma in one case each. There were 14 cases of glioblastoma (grade IV WHO) and 2 cases of astrocytoma (grade II WHO), with a mean latency time of 17 years (range: 6-26 years). For glioblastomas mean survival time was 10.4 months, accounting for 1-3% of all the glioblastomas treated. A thorough revision of the pertinent literature revealed some clinical-biological peculiarities.

  13. Daily Life Experiences of Patients With a High-Grade Glioma and Their Caregivers

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes;


    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs ...... for rehabilitation programs that target the cognitive ability of the patients to participate actively.......BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes...

  14. Optic glioma

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  15. Preliminary analysis of cellular sociology of co-cultured glioma initiating cells and macrophages in vitro

    Mingxia Zhang; Xingliang Dai; Xiaonan Li; Qiang Huang; Jun Dong; Junjie Chen; Lin Wang; Xiaoyan Ji; Lin Yang; Yujing Sheng; Hairui Liu; Haiyang Wang; Aidong Wang


    Objective:Real-time monitoring of cytokine secretion at the single immunocyte level, based on the concept of immune cells, sociology has been recently reported. However, the relationships between glioma-initiating cells (GICs) and host immune cells and their mutual interactions in the tumor microenvironment have not been directly observed and remain unclear. Methods:The dual fluorescence tracing technique was applied to label the co-cultured GICs and host macrophages (Mø), and the interactions between the two types of cells were observed using a live cell imaging system. Fusion cells in the co-culture system were monocloned and proliferated in vitro and their social interactions were observed and recorded. Results:Using real-time dynamic observation of target cells, 6 types of intercellular conjunction microtubes were found to function in the transfer of intercellular information between GICs and Mø;GICs and host Mø can fuse into hybrid cells after several rounds of mutual interactions, and then these fusion cells fused with each other;Fusion cells generated offspring cells through symmetrical and asymmetrical division or underwent apoptosis. A“cell in cell” phenomenon was observed in the fusion cells, which was often followed by cell release, namely entosis. Conclusions:Preliminary studies revealed the patterns of cell conjunction via microtubes between GICs and host Mø and the processes of cell fusion, division, and entosis. The results revealed malignant transformation of host Mø, induced by GICs, suggesting complex social relationships among tumor-immune cells in gliomas.

  16. Initial Egyptian ECMO experience

    Akram Abdelbary


    Results: A total of twelve patients received ECMO between January 2014 and June 2015. The mean age was 35.9 years. (range 13–65 years, 8 males, with VV ECMO in 10 patients, and VA ECMO in 2 patients. Out of ten patients of VV ECMO, one had H1N1 pneumonia, one had advanced vasculitic lung, four had bacterial pneumonia, two traumatic lung contusions and one with organophosphorus poisoning, and one undiagnosed etiology leading to severe ARDS. Lung injury score range was 3–3.8, PaO2/FiO2 (20–76 mechanical ventilation duration before ECMO 1–14 days, Femoro-jugular cannulation in 7 patients and femoro-femoral in 2 patients and femoro-subclavian in 1 patient; all patients were initially sedated and paralyzed for (2–4 days and ventilated on pressure controlled ventilation with Pmax of 25 cm H2O and PEEP of 10 cm H2O. In VA ECMO patients were cannulated percutaneously using femoro-femoral approach. One patient showed no neurologic recovery and died after 24 h, the other had CABG on ECMO however the heart didn’t recover and died after 9 days. Heparin intravenous infusion was used initially in all patients and changed to Bivalirudin in 2 patients due to possible HIT. Pump flow ranged from 2.6 to 6.5 L/min. Average support time was 12 days (range 2–24 days. Seven patients (63.3% were successfully separated from ECMO and survived to hospital discharge. Hospital length of stay ranged from 3 to 42 days, tracheostomy was done percutaneously in 5 patients and surgically in 3. Gastrointestinal bleeding occurred in 6 patients, VAP in 7 patients, neurologic complications in 1 patient with complete recovery, cardiac arrhythmias in 3 patients, pneumothorax in 9 patients, and deep venous thrombosis in 2 patients.



    ICE was built in 1977, using the modified bending magnets of the g-2 muon storage ring (see 7405430). Its purpose was to verify the validity of stochastic and electron cooling for the antiproton project. Stochastic cooling proved a resounding success early in 1978 and the antiproton project could go ahead, now entirely based on stochastic cooling. Electron cooling was experimented with in 1979. The 26 kV equipment is housed in the cage to the left of the picture, adjacent to the "e-cooler" located in a straight section of the ring. With some modifications, the cooler was later transplanted into LEAR (Low Energy Antiproton Ring) and then, with further modifications, into the AD (Antiproton Decelerator), where it cools antiprotons to this day (2006). See also: 7711282, 7802099, 7809081.

  18. Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin αV.

    Akiko Niibori-Nambu

    Full Text Available Glioma initiating cells (GICs are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanism of GIC maintenance/differentiation, we established GIC clones having the potential to differentiate into malignant gliomas, and subjected to DNA microarray/iTRAQ based integrated proteomics. 21,857 mRNAs and 8,471 proteins were identified and integrated into a gene/protein expression analysis chart. Gene Ontology analysis revealed that the expression of cell adhesion molecules, including integrin subfamilies, such as α2 and αV, and extracellular matrices (ECMs, such as collagen IV (COL4, laminin α2 (LAMA2, and fibronectin 1 (FN, was significantly upregulated during serum-induced GIC differentiation. This differentiation process, accompanied by the upregulation of MAPK as well as glioma specific proteins in GICs, was dramatically accelerated in these ECM (especially FN-coated dishes. Integrin αV blocking antibody and RGD peptide significantly suppressed early events in GIC differentiation, suggesting that the coupling of ECMs to integrin αV is necessary for GIC differentiation. In addition, the expression of integrin αV and its strong ligand FN was prominently increased in glioblastomas developed from mouse intracranial GIC xenografts. Interestingly, during the initial phase of GIC differentiation, the RGD treatment significantly inhibited GIC proliferation and raised their sensitivity against anti-cancer drug temozolomide (TMZ. We also found that combination treatments of TMZ and RGD inhibit glioma progression and lead the longer survival of mouse intracranial GIC xenograft model. These results indicate that GICs induce/secrete ECMs to develop microenvironments with serum factors, namely differentiation niches that further stimulate GIC differentiation and proliferation via the integrin recognition motif RGD. A combination of RGD treatment with TMZ could have the higher inhibitory


    Gish, Liv


    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... understandings of idea work are inscribed in the idea promoting initiatives as they to some degree have to fit with the understandings embedded in practice in order to work....


    Gish, Liv


    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... understandings of idea work are inscribed in the idea promoting initiatives as they to some degree have to fit with the understandings embedded in practice in order to work....

  1. A novel, integrated PET-guided MRS technique resulting in more accurate initial diagnosis of high-grade glioma.

    Kim, Ellen S; Satter, Martin; Reed, Marilyn; Fadell, Ronald; Kardan, Arash


    Glioblastoma multiforme (GBM) is the most common and lethal malignant glioma in adults. Currently, the modality of choice for diagnosing brain tumor is high-resolution magnetic resonance imaging (MRI) with contrast, which provides anatomic detail and localization. Studies have demonstrated, however, that MRI may have limited utility in delineating the full tumor extent precisely. Studies suggest that MR spectroscopy (MRS) can also be used to distinguish high-grade from low-grade gliomas. However, due to operator dependent variables and the heterogeneous nature of gliomas, the potential for error in diagnostic accuracy with MRS is a concern. Positron emission tomography (PET) imaging with (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) has been shown to add additional information with respect to tumor grade, extent, and prognosis based on the premise of biochemical changes preceding anatomic changes. Combined PET/MRS is a technique that integrates information from PET in guiding the location for the most accurate metabolic characterization of a lesion via MRS. We describe a case of glioblastoma multiforme in which MRS was initially non-diagnostic for malignancy, but when MRS was repeated with PET guidance, demonstrated elevated choline/N-acetylaspartate (Cho/NAA) ratio in the right parietal mass consistent with a high-grade malignancy. Stereotactic biopsy, followed by PET image-guided resection, confirmed the diagnosis of grade IV GBM. To our knowledge, this is the first reported case of an integrated PET/MRS technique for the voxel placement of MRS. Our findings suggest that integrated PET/MRS may potentially improve diagnostic accuracy in high-grade gliomas.

  2. A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

    Katherine L. Misuraca


    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53fl/fl mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP− and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease.

  3. Machine learning methods for the classification of gliomas: Initial results using features extracted from MR spectroscopy.

    Ranjith, G; Parvathy, R; Vikas, V; Chandrasekharan, Kesavadas; Nair, Suresh


    With the advent of new imaging modalities, radiologists are faced with handling increasing volumes of data for diagnosis and treatment planning. The use of automated and intelligent systems is becoming essential in such a scenario. Machine learning, a branch of artificial intelligence, is increasingly being used in medical image analysis applications such as image segmentation, registration and computer-aided diagnosis and detection. Histopathological analysis is currently the gold standard for classification of brain tumors. The use of machine learning algorithms along with extraction of relevant features from magnetic resonance imaging (MRI) holds promise of replacing conventional invasive methods of tumor classification. The aim of the study is to classify gliomas into benign and malignant types using MRI data. Retrospective data from 28 patients who were diagnosed with glioma were used for the analysis. WHO Grade II (low-grade astrocytoma) was classified as benign while Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma multiforme) were classified as malignant. Features were extracted from MR spectroscopy. The classification was done using four machine learning algorithms: multilayer perceptrons, support vector machine, random forest and locally weighted learning. Three of the four machine learning algorithms gave an area under ROC curve in excess of 0.80. Random forest gave the best performance in terms of AUC (0.911) while sensitivity was best for locally weighted learning (86.1%). The performance of different machine learning algorithms in the classification of gliomas is promising. An even better performance may be expected by integrating features extracted from other MR sequences. © The Author(s) 2015 Reprints and permissions:

  4. Establishment of human iPSC-based models for the study and targeting of glioma initiating cells

    Sancho-Martinez, Ignacio; Nivet, Emmanuel; Xia, Yun; Hishida, Tomoaki; Aguirre, Aitor; Ocampo, Alejandro; Ma, Li; Morey, Robert; Krause, Marie N.; Zembrzycki, Andreas; Ansorge, Olaf; Vazquez-Ferrer, Eric; Dubova, Ilir; Reddy, Pradeep; Lam, David; Hishida, Yuriko; Wu, Min-Zu; Esteban, Concepcion Rodriguez; O'Leary, Dennis; Wahl, Geoffrey M.; Verma, Inder M.; Laurent, Louise C.; Izpisua Belmonte, Juan Carlos


    Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis. PMID:26899176

  5. Energy efficiency initiatives: Indian experience

    Dey, Dipankar [ICFAI Business School, Kolkata, (IBS-K) (India)


    India, with a population of over 1.10 billion is one of the fastest growing economies of the world. As domestic sources of different conventional commercial energy are drying up, dependence on foreign energy sources is increasing. There exists a huge potential for saving energy in India. After the first 'oil shock' (1973), the government of India realized the need for conservation of energy and a 'Petroleum Conservation Action Group' was formed in 1976. Since then many initiatives aiming at energy conservation and improving energy efficiency, have been undertaken (the establishment of Petroleum Conservation Research Association in 1978; the notification of Eco labelling scheme in 1991; the formation of Bureau of Energy Efficiency in 2002). But no such initiative was successful. In this paper an attempt has been made to analyze the changing importance of energy conservation/efficiency measures which have been initiated in India between 1970 and 2005.The present study tries to analyze the limitations and the reasons of failure of those initiatives. The probable reasons are: fuel pricing mechanism (including subsidies), political factors, corruption and unethical practices, influence of oil and related industry lobbies - both internal and external, the economic situation and the prolonged protection of domestic industries. Further, as India is opening its economy, the study explores the opportunities that the globally competitive market would offer to improve the overall energy efficiency of the economy. The study suggests that the Bureau of Energy Efficiency (BEE) - the newly formed nodal agency for improving energy efficiency of the economy may be made an autonomous institution where intervention from the politicians would be very low. For proper implementation of different initiatives to improve energy efficiency, BEE should involve more the civil societies (NGO) from the inception to the implementation stage of the programs. The paper also

  6. A high Notch pathway activation predicts response to γ secretase inhibitors in proneural subtype of glioma tumor-initiating cells.

    Saito, Norihiko; Fu, Jun; Zheng, Siyuan; Yao, Jun; Wang, Shuzhen; Liu, Diane D; Yuan, Ying; Sulman, Erik P; Lang, Frederick F; Colman, Howard; Verhaak, Roel G; Yung, W K Alfred; Koul, Dimpy


    Genomic, transcriptional, and proteomic analyses of brain tumors reveal subtypes that differ in pathway activity, progression, and response to therapy. However, a number of small molecule inhibitors under development vary in strength of subset and pathway-specificity, with molecularly targeted experimental agents tending toward stronger specificity. The Notch signaling pathway is an evolutionarily conserved pathway that plays an important role in multiple cellular and developmental processes. We investigated the effects of Notch pathway inhibition in glioma tumor-initiating cell (GIC, hereafter GIC) populations using γ secretase inhibitors. Drug cytotoxicity testing of 16 GICs showed differential growth responses to the inhibitors, stratifying GICs into responders and nonresponders. Responder GICs had an enriched proneural gene signature in comparison to nonresponders. Also gene set enrichment analysis revealed 17 genes set representing active Notch signaling components NOTCH1, NOTCH3, HES1, MAML1, DLL-3, JAG2, and so on, enriched in responder group. Analysis of The Cancer Genome Atlas expression dataset identified a group (43.9%) of tumors with proneural signature showing high Notch pathway activation suggesting γ secretase inhibitors might be of potential value to treat that particular group of proneural glioblastoma (GBM). Inhibition of Notch pathway by γ secretase inhibitor treatment attenuated proliferation and self-renewal of responder GICs and induces both neuronal and astrocytic differentiation. In vivo evaluation demonstrated prolongation of median survival in an intracranial mouse model. Our results suggest that proneural GBM characterized by high Notch pathway activation may exhibit greater sensitivity to γ secretase inhibitor treatment, holding a promise to improve the efficiency of current glioma therapy.

  7. Robonaut Mobile Autonomy: Initial Experiments

    Diftler, M. A.; Ambrose, R. O.; Goza, S. M.; Tyree, K. S.; Huber, E. L.


    A mobile version of the NASA/DARPA Robonaut humanoid recently completed initial autonomy trials working directly with humans in cluttered environments. This compact robot combines the upper body of the Robonaut system with a Segway Robotic Mobility Platform yielding a dexterous, maneuverable humanoid ideal for interacting with human co-workers in a range of environments. This system uses stereovision to locate human teammates and tools and a navigation system that uses laser range and vision data to follow humans while avoiding obstacles. Tactile sensors provide information to grasping algorithms for efficient tool exchanges. The autonomous architecture utilizes these pre-programmed skills to form complex behaviors. The initial behavior demonstrates a robust capability to assist a human by acquiring a tool from a remotely located individual and then following the human in a cluttered environment with the tool for future use.

  8. Effects of Photodynamic Therapy on the Ultrastructure of Glioma Cells


    Objective To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. Methods The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. Results Apoptosis in different phases and necrosis could be observed in some C6 glioma cells.Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells.Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile,limited impact on the normal sub-cellular structures and BBB was observed. Conclusion PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

  9. Multiple Gliomas


    Multiple gliomas are well-recognized but uncommon tumors. The incidence of multiple gliomas according to some reports ranges from 0.5% to 20% of all gliomas diagnosed. Multiple gliomas can be divided into two categories. One is by location of the lesions (multifocal and multicentric). The second type is by the time of the lesions occur (synchronous and metachronous). The lesions generally show hypo, or isodensity on CT; a hypo- or isointense signal on T1-weighted images, and a hyperintense signal on T2-weighted images. Glioblastoma is the most frequent histotype. The prognosis of multiple gliomas remains unfavorable. The treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Distinction between multicentric and multifocal gliomas is difficult. This report reviews in detail the aspects of multiple gliomas mentioned above.

  10. Return to Experience and Initial Wage Level

    Sørensen, Kenneth Lykke; Vejlin, Rune Majlund

    This paper estimates the relationship between initial wage and return to experience. We use a Mincer-like wage model to nonparametrically estimate this relationship allowing for an unobservable individual permanent effect in wages and unobservable individual return to experience. The relationship...

  11. Return to experience and initial wage level

    Sørensen, K.L.; Vejlin, R.


    This paper estimates the relationship between initial wage and return to experience. We use a Mincer-like wage model to non-parametrically estimate this relationship allowing for an unobservable individual permanent effect in wages and unobservable individual return to experience. The relationshi...

  12. Initial conditions of radiative shock experiments

    Kuranz, C. C.; Drake, R. P.; Krauland, C. M.; Marion, D. C.; Grosskopf, M. J.; Rutter, E.; Torralva, B.; Holloway, J. P. [Department of Atmospheric, Oceanic and Space Science, University of Michigan, Center for Radiative Shock Hydrodynamics, 2455 Hayward Dr., Ann Arbor, Michigan 48109 (United States); Bingham, D.; Goh, J. [Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC, Canada V5A 1S6 (Canada); Boehly, T. R.; Sorce, A. T. [Laboratory for Laser Energetics, University of Rochester, New York 14623 (United States)


    We performed experiments at the Omega Laser Facility to characterize the initial, laser-driven state of a radiative shock experiment. These experiments aimed to measure the shock breakout time from a thin, laser-irradiated Be disk. The data are then used to inform a range of valid model parameters, such as electron flux limiter and polytropic γ, used when simulating radiative shock experiments using radiation hydrodynamics codes. The characterization experiment and the radiative shock experiment use a laser irradiance of ∼7 × 10{sup 14} W cm{sup −2} to launch a shock in the Be disk. A velocity interferometer and a streaked optical pyrometer were used to infer the amount of time for the shock to move through the Be disk. The experimental results were compared with simulation results from the Hyades code, which can be used to model the initial conditions of a radiative shock system using the CRASH code.

  13. Genetic Alterations in Glioma

    Bralten, Linda B. C.; French, Pim J., E-mail: [Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam (Netherlands)


    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

  14. Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.

    Baker, Gregory J; Chockley, Peter; Yadav, Viveka Nand; Doherty, Robert; Ritt, Michael; Sivaramakrishnan, Sivaraj; Castro, Maria G; Lowenstein, Pedro R


    Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1-deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1-expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079-90. ©2014 AACR. ©2014 American Association for Cancer Research.

  15. Initial state radiation experiment at MAMI

    Mihovilovič M.


    Full Text Available In an attempt to contribute further insight into the discrepancy between the Lamb shift and elastic scattering determinations of the proton charge radius, a new experiment at MAMI is underway, aimed at measuring proton form-factors at very low momentum transfers by using a new technique based on initial state radiation. This paper reports on the conclusions of the pilot measurement performed in 2010, whose main goal was to check the feasibility of the proposed experiment and to recognize and overcome any obstacles before running the full experiment. The modifications to the experimental apparatus are then explained which significantly improved the quality of data collected in the full scale experiment, which was successfully executed in August 2013. At the end first findings of the new experiment are discussed.

  16. {sup 123}I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients

    Keyaerts, Marleen; Lahoutte, Tony; Caveliers, Vicky; Vanhove, Chris; Franken, Philippe R.; Bossuyt, Axel [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium); ICMIC Brussels, Vrije Universiteit Brussel VUB, In Vivo Cellular and Molecular Imaging Center, Brussels (Belgium); Neyns, Bart [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Medical Oncology, Oncologisch Centrum, Brussels (Belgium); Everaert, Hendrik; Kersemans, Ken; Mertens, John [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium)


    {sup 123}I-2-iodo-tyrosine ({sup 123}I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. For the biodistribution study, six male volunteers received 60-95 MBq {sup 123}I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of {sup 123}I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. {sup 123}I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, {sup 123}I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). {sup 123}I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients. (orig.)

  17. Exploratory Visual Analysis of Statistical Results from Microarray Experiments Comparing High and Low Grade Glioma

    Jason H. Moore


    Full Text Available The biological interpretation of gene expression microarray results is a daunting challenge. For complex diseases such as cancer, wherein the body of published research is extensive, the incorporation of expert knowledge provides a useful analytical framework. We have previously developed the Exploratory Visual Analysis (EVA software for exploring data analysis results in the context of annotation information about each gene, as well as biologically relevant groups of genes. We present EVA as a fl exible combination of statistics and biological annotation that provides a straightforward visual interface for the interpretation of microarray analyses of gene expression in the most commonly occurring class of brain tumors, glioma. We demonstrate the utility of EVA for the biological interpretation of statistical results by analyzing publicly available gene expression profi les of two important glial tumors. The results of a statistical comparison between 21 malignant, high-grade glioblastoma multiforme (GBM tumors and 19 indolent, low-grade pilocytic astrocytomas were analyzed using EVA. By using EVA to examine the results of a relatively simple statistical analysis, we were able to identify tumor class-specifi c gene expression patterns having both statistical and biological signifi cance. Our interactive analysis highlighted the potential importance of genes involved in cell cycle progression, proliferation, signaling, adhesion, migration, motility, and structure, as well as candidate gene loci on a region of Chromosome 7 that has been implicated in glioma. Because EVA does not require statistical or computational expertise and has the fl exibility to accommodate any type of statistical analysis, we anticipate EVA will prove a useful addition to the repertoire of computational methods used for microarray data analysis. EVA is available at no charge to academic users and can be found at

  18. Initial Commissioning Experience With the LCLS Injector

    Akre, R.; Castro, J.; Ding, Y.; Dowell, D.H.; Emma, P.; Frisch, J.; Gilevich, A.; Hays, G.; Hering, P.; Huang, Z.; Iverson, R.; Krejcik, P.; Limborg-Deprey, C.; Loos, H.; Miahnahri, A.; Rivetta, C.; Saleski, M.; Schmerge, J.F.; Schultz, D.; Turner, J.; Welch, J.; /SLAC /DESY


    The Linac Coherent Light Source (LCLS) is a SASE xray Free-Electron Laser (FEL) project presently under construction at SLAC [1]. The injector section, from drive-laser and RF photocathode gun through first bunch compressor chicane, was installed in fall 2006. Initial system commissioning with an electron beam is taking place during the spring and summer of 2007. The second phase of construction, including second bunch compressor and full linac, will begin later, in the fall of 2007. We report here on experience gained during the first phase of machine commissioning, including RF photocathode gun, linac booster section, S-band and X-band RF systems, first bunch compressor, and the various beam diagnostics.

  19. Barrier experiment: Shock initiation under complex loading

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

  20. First experiences in treatment of low-grade glioma grade I and II with proton therapy


    Background To retrospectively assess feasibility and toxicity of proton therapy in patients with low-grade glioma (WHO °I/II). Patients and methods Proton beam therapy only administered in 19 patients (median age 29 years; 9 female, 10 male) for low-grade glioma between 2010 and 2011 was reviewed. In 6 cases proton therapy was performed due to tumor progression after biopsy, in 8 cases each due to tumor progression after (partial-) resection, and in 5 cases due to tumor progression after chemotherapy. Median total dose applied was 54 GyE (range, 48,6-54 GyE) in single fractions of median 1.8 GyE. Median clinical target volume was 99 cc (range, 6–463 cc) and treated using median 2 beams (range, 1–2). Results Proton therapy was finished as planned in all cases. At end of proton therapy, 13 patients showed focal alopecia, 6 patients reported mild fatigue, one patient with temporal tumor localization concentration deficits and speech errors and one more patient deficits in short-term memory. Four patients did not report any side effects. During follow-up, one patient presented with pseudo-progression showing worsening of general condition and brain edema 1–2 months after last irradiation and restitution after 6 months. In the present MR imaging (median follow-up 5 months; range 0–22 months) 12 patients had stable disease, 2 (1) patients partial (complete) remission, one more patient pseudo-progression (differential diagnosis: tumor progression) 4 weeks after irradiation without having had further follow-up imaging so far, and one patient tumor progression approximately 9 months after irradiation. Conclusion Regarding early side effects, mild alopecia was the predominant finding. The rate of alopecia seems to be due to large treatment volumes as well as the anatomical locations of the target volumes and might be avoided by using multiple beams and the gantry in the future. Further evaluations including neuropsychological testing are in preparation. PMID

  1. Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

    Connolly, Nina P; Stokum, Jesse A; Schneider, Craig S; Ozawa, Tatsuya; Xu, Su; Galisteo, Rebeca; Castellani, Rudolph J; Kim, Anthony J; Simard, J Marc; Winkles, Jeffrey A; Holland, Eric C; Woodworth, Graeme F


    Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS) virus / tumor virus receptor-A (tv-a) transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a) transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI) and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

  2. Radiotherapy for brainstem gliomas in children and adults: A single-institution experience and literature review.

    Yoshida, Kenji; Sulaiman, Nor Shazrina; Miyawaki, Daisuke; Ejima, Yasuo; Nishimura, Hideki; Ishihara, Takeaki; Matsuo, Yoshiro; Nishikawa, Ryo; Sasayama, Takashi; Hayakawa, Akira; Kohmura, Eiji; Sasaki, Ryohei


    To evaluate the treatment results of radiotherapy (RT) in children and adults with brainstem gliomas (BSGs) and review the previous literature. Thirty patients (14 children, 16 adults) with BSG treated using RT were retrospectively evaluated. The median ages of the children and adults were 8 years (range: 2-16 years) and 49 years (range: 19-75 years), respectively. A histological diagnosis was obtained in 11 patients. The median total radiation dose was 56 Gy (range: 50-70 Gy) with a single fraction size of 1.8-2.0 Gy. Temozolomide was administered concurrently with RT in 14 patients. Tumor progression after RT occurred in 26 patients (14 children and 12 adults). Four adults survived without tumor progression. The median survival times for children and adults were 8.5 and 39 months, respectively. The 1-, 2- and 3-year overall survival rates for children/adults were 29%/75%, 14%/68% and 0%/53%, respectively (P = 0.001), and the 1-, 2- and 3-year progression-free survival rates for children/adults were 14%/69%, 0%/49% and 0%/35%, respectively (P adults, and our results are consistent with those of previous studies. Efforts should be made to improve the survival outcomes of patients with BSGs, especially children. © 2016 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

  3. Liver transplantations in Bulgaria--initial experience.

    Vladov, N; Mihaylov, V; Takorov, I; Vasilevski, I; Lukanova, T; Odisseeva, E; Katzarov, K; Simonova, M; Tomova, D; Konakchieva, M; Petrov, N; Mladenov, N; Sergeev, S; Mutafchiiski, V


    The filed of liver transplantation (LT) continues to evolve and is highly effective therapy for many patients with acute and chronic liver failure resulting from a variety of causes. Improvement of perioperative care, surgical technique and immunosuppression in recent years has led to its transformation into a safe and routine procedure with steadily improving results. The aim of this paper is to present the initial experience of the transplant team at Military Medical Academy - Sofia, Bulgaria. For the period of April 2007 - August 2014 the team performed 38 liver transplants in 37 patients (one retransplantation). Patients were followed up prospectively and retrospectively. In 36 (95%) patients a graft from a cadaveric donor was used and in two cases--a right liver grafts from live donor. The mean MELD score of the transplanted patients was 17 (9-40). The preferred surgical technique was "piggyback" with preservation of inferior vena cava in 33 (86%) of the cases and classical technique in 3 (8%) patients. The overall complication rate was 48%. Early mortality rate was 13% (5 patients). The overall 1- and 5-year survival is 81% and 77% respectivelly. The setting of a new LT program is a complex process which requires the effort and effective colaboration of a wide range of speciacialists (hepatologists, surgeons, anesthesiologists, psychologists, therapists, coordinators, etc.) and institutions. The good results are function of a proper selection of the donors and the recipients. Living donation is an alternative in the shortage of cadaveric donors.

  4. Gene Therapy for Gliomas

    Nanda, Dharminderkoemar


    textabstractThe overall median survival in glioblastoma multiforme (GBM) patients is less than one year and fewer than 5% of patients survive more than 5 years. The current standard of care for GBM patients involves neurosurgical resection of the tumor followed by radiotherapy with concomitant and adjuvant temozolomide chemotherapy. After initial treatment, all malignant gliomas eventually recur, mostly within a 2-3 cm margin of the original tumor on CT/MRI. The poor prognosis warrants resear...

  5. Experiences of Racism in Initial Teacher Education.

    Garewal, Gurpreet


    Explores trainee teachers' perceptions and projections of racial discrimination while taking the postcompulsory teaching course in England. Experiences of four trainee teachers highlight the need for more support for teacher trainees, more cultural sensitivity among teacher educators, and the inclusion of cultural and racial issues in the course.…

  6. Initial experiments with Multiple Musical Gestures

    Jensen, Kristoffer; Graugaard, Lars


    The classic orchestra has a diminishing role in society, while hard-disc recorded music plays a predominant role today. A simple to use pointer interface in 2D for producing music is presented as a means for playing in a social situation. The sounds of the music are produced by a low......-level synthesizer, and the music is produced by simple gestures that are repeated easily. The gestures include left-to-right and right-to-left motion shapes for spectral envelope and temporal envelope of the sounds, with optional backwards motion for the addition of noise; downward motion for note onset and several...... other manipulation gestures. The initial position controls which parameter is being affected, the notes intensity is controlled by the downward gesture speed, and a sequence is finalized instantly with one upward gesture. The synthesis employs a novel interface structure, the multiple musical gesture...

  7. Women's initial experience of abnormal papanicolaou smear.

    Mitchell, Susan; Hall, Vincent P


    To discover the early subjective experience of women affected by abnormal Papanicolaou smear, a qualitative study was undertaken with 8 North Carolina women, 4 to 12 months postnotification of their first abnormal result. Data were analyzed via grounded theory methodology to identify a core theory that could guide interventions to improve follow-up for cancer prevention. This theoretical process is described as a labyrinth journey-an imperative healing process undertaken by all participants, who undertook the following tasks: evaluating peril, seeking refuge, obtaining information, and reframing their self-image. Women who also learned they were infected with the human papillomavirus faced a prolonged sense of threat to their sense of sexual well-being. Their additional tasks related to reevaluating their sexual self-image, and they continued to work on these reframing tasks throughout their 1st year's journey. Progress through the labyrinth depended upon emotional or spiritual support, nonjudgmental acceptance and access to accurate information.

  8. SNS Target Systems initial operating experience

    McManamy, T.; Forester, J.


    The SNS mercury target started operation with low beam power when commissioned on April 28, 2006. The beam power has been following a planned ramp up since then and has reached 340 kW as of February 2008. The target systems supporting neutron production include the target and mercury loop, the cryogenic and ambient moderator systems, reflector and vessel systems, bulk shielding and shutters systems, utility systems, remote handling systems and the associated instrumentation and controls. Availability for these systems has improved with time and reached 100% for the first 2000 hour neutron production run in fiscal year 2008. An overview of the operating experience and the planning to support continued power increases to 1.4 MW for these systems will be given in this paper.

  9. Initial experience with robot-assisted varicocelectomy

    Tung Shu; Shaya Taghechian; Run Wang


    Aim: To determine if robot-assisted varicocelectomy can be safely and effectively performed when compared microscopic inguinal varicocelectomy. Methods: Eight patients aged 29.1 ± 12.5 years underwent microscopic subinguinal varicocelectomies: seven patients with left-sided repair, and one patient with bilateral repair. Eight patients aged 22.0 ± 8.0 years underwent robot-assisted varicocelectomies: seven patients with left-sided repair and one patient with bilateral repair. Results: The average operative time for microscopic inguinal varicocelectomy was 73.9 ± 12.2 min, whereas the robot-assisted technique took 71.1 ± 21.1 min. There were no difficulties in identifying and isolating vessels and the vas deferens with robot-assisted subinguinal varicocelectomy. Hand tremor was eliminated using the robotic procedure. Patients who underwent either microscopic or robot-assisted varicocelectomies were able to resume daily activities on the day of surgery and full activities within 2 weeks. There were complications or recurrences of varicocele. Conclusion: From our experience, compared to microscopic surgery,robot-assisted varicocelectomy can be safely and effectively performed, with the added benefit of eliminating hand tremor.

  10. Initial performance of the CUORE-0 experiment

    Artusa, D.R. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); Avignone, F.T.; Chott, N.; Creswick, R.J.; Farach, H.A.; Rosenfeld, C.; Wilson, J. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); Azzolini, O.; Keppel, G.; Palmieri, V. [INFN-Laboratori Nazionali di Legnaro, Padua (Italy); Balata, M.; Bucci, C.; Canonica, L.; Casali, N.; Di Vacri, M.L.; Goett, J.; Gorla, P.; Nisi, S.; Orlandi, D.; Pattavina, L.; Pirro, S.; Zarra, C. [INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); Banks, T.I. [INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Bari, G.; Deninno, M.M.; Moggi, N. [INFN-Sezione di Bologna, Bologna (Italy); Beeman, J. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); Bellini, F.; Cardani, L.; Cosmelli, C.; Ferroni, F.; Piperno, G. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Bersani, A. [INFN-Sezione di Genova, Genoa (Italy); Biassoni, M.; Brofferio, C.; Capelli, S.; Carrettoni, M.; Chiesa, D.; Clemenza, M.; Faverzani, M.; Ferri, E.; Fiorini, E.; Giachero, A.; Gironi, L.; Gotti, C.; Maiano, C.; Maino, M.; Nucciotti, A.; Pavan, M.; Sala, E.; Sisti, M.; Terranova, F.; Zanotti, L. [Universita di Milano-Bicocca, Dipartimento di Fisica, Milan (Italy); INFN-Sezione di Milano Bicocca, Milan (Italy); Cai, X.Z.; Cao, X.G.; Fang, D.Q.; Li, Y.L.; Ma, Y.G.; Tian, W.D.; Wang, H.W. [Shanghai Institute of Applied Physics (Chinese Academy of Sciences), Shanghai (China); Carbone, L.; Cremonesi, O.; Datskov, V.; Pessina, G.; Previtali, E.; Rusconi, C. [INFN-Sezione di Milano Bicocca, Milan (Italy); Dafinei, I.; Morganti, S.; Orio, F.; Pettinacci, V.; Tomei, C.; Vignati, M. [INFN-Sezione di Roma, Rome (Italy); Dally, A.; Ejzak, L.; Wielgus, L. [University of Wisconsin, Department of Physics, Madison, WI (United States); Di Domizio, S.; Fernandes, G.; Pallavicini, M. [INFN-Sezione di Genova, Genoa (Italy); Universita di Genova, Dipartimento di Fisica, Genoa (Italy); Freedman, S.J. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Fujikawa, B.K.; Han, K.; Mei, Y. [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Giuliani, A.; Tenconi, M. [Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse, Orsay Campus (France); Gutierrez, T.D. [California Polytechnic State University, Physics Department, San Luis Obispo, CA (United States); Haller, E.E. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); University of California, Department of Materials Science and Engineering, Berkeley, CA (United States); Heeger, K.M.; Lim, K.E.; Maruyama, R.H. [Yale University, Department of Physics, New Haven, CT (United States); Hennings-Yeomans, R.; Ouellet, J.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Huang, H.Z.; Liu, X.; Trentalange, S.; Winslow, L.A.; Zhu, B.X. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Kadel, R. [Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Kazkaz, K.; Pedretti, M.; Sangiorgio, S.; Scielzo, N.D. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Kolomensky, Yu.G. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Martinez, M. [Universidad de Zaragoza, Laboratorio de Fisica Nuclear y Astroparticulas, Saragossa (Spain); Nones, C. [Service de Physique des Particules, CEA/Saclay, Gif-sur-Yvette (France); Norman, E.B.; Wang, B.S. [Lawrence Livermore National Laboratory, Livermore, CA (United States); University of California, Department of Nuclear Engineering, Berkeley, CA (United States); O' Donnell, T. [University of California, Department of Physics, Berkeley, CA (United States); Smith, A.R. [Lawrence Berkeley National Laboratory, EH and S Division, Berkeley, CA (United States); Taffarello, L. [INFN-Sezione di Padova, Padua (Italy); Ventura, G. [Universita di Firenze, Dipartimento di Fisica, Florence (Italy); INFN-Sezione di Firenze, Florence (Italy); Wise, T. [University of Wisconsin, Department of Physics, Madison, WI (United States); Yale University, Department of Physics, New Haven, CT (United States); Zucchelli, S. [INFN-Sezione di Bologna, Bologna (Italy); Universita di Bologna, Dipartimento di Fisica, Bologna (Italy)


    CUORE-0 is a cryogenic detector that uses an array of tellurium dioxide bolometers to search for neutrinoless double-beta decay of {sup 130}Te. We present the first data analysis with 7.1kg . y of total TeO{sub 2} exposure focusing on background measurements and energy resolution. The background rates in the neutrinoless double-beta decay region of interest (2.47 to 2.57MeV) and in the α backgrounddominated region (2.70 to 3.90 MeV) have been measured to be 0.071 ± 0.011 and 0.019 ± 0.002 counts/(keV . kg . y), respectively. The latter result represents a factor of 6 improvement from a predecessor experiment, Cuoricino. The results verify our understanding of the background sources in CUORE-0, which is the basis of extrapolations to the full CUORE detector. The obtained energy resolution (full width at half maximum) in the region of interest is 5.7 keV. Based on themeasured background rate and energy resolution in the region of interest, CUORE-0 half-life sensitivity is expected to surpass the observed lower bound of Cuoricino with one year of live time. (orig.)

  11. Initial performance of the CUORE-0 experiment

    Aguirre, C P; Avignone, F T; Azzolini, O; Balata, M; Banks, T I; Bari, G; Beeman, J; Bellini, F; Bersani, A; Biassoni, M; Brofferio, C; Bucci, C; Cai, X Z; Canonica, L; Cao, X G; Capelli, S; Carbone, L; Cardani, L; Carrettoni, M; Casali, N; Chiesa, D; Chott, N; Clemenza, M; Cosmelli, C; Cremonesi, O; Creswick, R J; Dafinei, I; Dally, A; Datskov, V; Deninno, M M; Di Domizio, S; di Vacri, M L; Ejzak, L; Fang, D Q; Farach, H A; Faverzani, M; Fernandes, G; Ferri, E; Ferroni, F; Fiorini, E; Freedman, S J; Fujikawa, B K; Giachero, A; Gironi, L; Giuliani, A; Goett, J; Gorla, P; Gotti, C; Gutierrez, T D; Haller, E E; Han, K; Heeger, K M; Hennings-Yeomans, R; Huang, H Z; Kadel, R; Kazkaz, K; Keppel, G; Kolomensky, Yu G; Li, Y L; Lim, K E; Liu, X; Ma, Y G; Maiano, C; Maino, M; Martinez, M; Maruyama, R H; Mei, Y; Moggi, N; Morganti, S; Nisi, S; Nones, C; Norman, E B; Nucciotti, A; O'Donnell, T; Orio, F; Orlandi, D; Ouellet, J L; Pallavicini, M; Palmieri, V; Pattavina, L; Pavan, M; Pedretti, M; Pessina, G; Pettinacci, V; Piperno, G; Pirro, S; Previtali, E; Rosenfeld, C; Rusconi, C; Sala, E; Sangiorgio, S; Scielzo, N D; Sisti, M; Smith, A R; Taffarello, L; Tenconi, M; Terranova, F; Tian, W D; Tomei, C; Trentalange, S; Vignati, M; Wang, B S; Wang, H W; Wielgus, L; Wilson, J; Winslow, L A; Wise, T; Zanotti, L; Zarra, C; Zhu, B X; Zucchelli, S


    CUORE-0 is a cryogenic detector that uses an array of tellurium dioxide bolometers to search for neutrinoless double-beta decay of ^{130}Te. We present the first data analysis with 7.1 kg y of total TeO_2 exposure focusing on background measurements and energy resolution. The background rates in the neutrinoless double-beta decay region of interest (2.47 to 2.57 MeV) and in the {\\alpha} background-dominated region (2.70 to 3.90 MeV) have been measured to be 0.071 \\pm 0.011 and 0.019 \\pm 0.002 counts/keV/kg/y, respectively. The latter result represents a factor of 6 improvement from a predecessor experiment, Cuoricino. The results verify our understanding of the background sources in CUORE-0, which is the basis of extrapolations to the full CUORE detector. The obtained energy resolution (full width at half maximum) in the region of interest is 5.7 keV. Based on the measured background rate and energy resolution in the region of interest, CUORE-0 half-life sensitivity is expected to surpass the observed lower b...

  12. Laparoscopic nephrectomy: initial experience with 120 cases.

    Cheema, I A


    Laparoscopic nephrectomy for both benign and malignant diseases of kidney is increasingly being performed. We report our experience with the first 120 consecutive laparoscopic nephrectomy performed in our hospital. It is the retrospective analysis of a prospectively maintained database of 4 years period. The parameters examined included age, gender, indications, operative time, blood loss, intraoperative and post operative complications. Mean age of surgery was 59 years (rang 19-84years). The indications for surgery included solid renal masses (71 patients), non-functioning kidneys (43), and collecting system tumours (6). The mean operating time was 132 minutes (range 75-270), average blood loss was 209 ml (range 0-1090) and average hospital stay was 4.7days (range 2-20). Bleeding, bowel injury and poor progression of laparoscopic procedure were the reasons in 7 (5.8%) cases converted to open surgery. There was 1 (0.8%) perioperative mortality. Eight (6.6%) patients developed post operative complications. Laparoscopic nephrectomy has inherent benefits and may be considered an alternate therapeutic option for kidney diseases with acceptable morbidity

  13. Laparoscopic nephrectomy: initial experience with 120 cases.

    Cheema, I A


    Laparoscopic nephrectomy for both benign and malignant diseases of kidney is increasingly being performed. We report our experience with the first 120 consecutive laparoscopic nephrectomy performed in our hospital. It is the retrospective analysis of a prospectively maintained database of 4 years period. The parameters examined included age, gender, indications, operative time, blood loss, intraoperative and post operative complications. Mean age of surgery was 59 years (rang 19-84years). The indications for surgery included solid renal masses (71 patients), non-functioning kidneys (43), and collecting system tumours (6). The mean operating time was 132 minutes (range 75-270), average blood loss was 209 ml (range 0-1090) and average hospital stay was 4.7days (range 2-20). Bleeding, bowel injury and poor progression of laparoscopic procedure were the reasons in 7 (5.8%) cases converted to open surgery. There was 1 (0.8%) perioperative mortality. Eight (6.6%) patients developed post operative complications. Laparoscopic nephrectomy has inherent benefits and may be considered an alternate therapeutic option for kidney diseases with acceptable morbidity

  14. Experimental Research on Human Glioma with 20- Year Experiences%人脑胶质瘤研究20年

    黄强; 兰青; 董军; 杜子威


    [目的]总结人脑胶质瘤研究20年的经验,探讨进一步研究策略。[方法]回顺1980至2000年在人脑胶质瘤的模型制作、化疗实验、抗体制备与应用、诱导分化、生物治疗等方面的创新点和不足之处的改进。[结果]创新.建立了中国第一个人脑胶质瘤体外细胞系SHG44及其可移植性裸小鼠模型NHG-1、杂交瘤单抗细胞株SZ38和SZ39及其在生物导向珍治中的应用、详细观察诱导分化剂HMBA和DMF的促分化效应等改进,从SHG-44中克隆出具有高·中·低三个不同分化程度的细胞株、建立人鼠肿瘤免疫嵌合模型以弥补NHG-I不能用于生物免疫治疗的不足、SU2000替代效价不断下降的SZ39、基因工程改造SZ39为seFv、Fab/Hu、ScFv/TNF、seFv/PE40和化学偶联SZ39Fab/CD3Fab等小分子·低免疫原·双功能抗体[结论]胶质瘤研究举步为艰,随着分子生物学研究的深入和人类DNA密码的破译,传统治疗加生物·免疫和基因治疗有可能永久性治愈胶质瘤%[Purpose] To summarize our researeh proeess in twenty years on human glioma for the purpose of coneeiving new ideas andslrategy on glioma research. [Methods] Six aspects of the experimental study on glioma during 1980 to 2000 were reviewed. ineluding tumormodels preparation. experimenial ehemotherapy, anti-glioma monoclonal antibodies (hmAb) preparation and their application. induced differentia-tion therapy and biological therapy, etc..Some tentative plans are put forvard on the basis of analysis on both of the creative viewpoints andlimitations of every aspects. [Resnlts] (1) We established the first human glioma cell line in China, named SHG-44 and the nude mice solid tumor(glioma) model NHG-1. (2) The hybridoma cell line SZ39 and SZ38 were established in 1988 which can stably secrele anti-glioma monoclonalantibodies. and were widely used in the targeting diagnosis and therapy against human glioma. (3) The differentiation promoling

  15. Initial predictions in learning-to-forecast experiment

    C. Diks; T. Makarewicz


    In this paper we estimate the distribution of the initial predictions of the Heemeijer et al. [5] Learning-to-Forecast experiment. By design, these initial predictions were uninformed. We show that in fact they have a non-continuous distribution and that they systematically under-evaluate the fundam

  16. Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients

    Combs, Stephanie E. (Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)), E-mail:; Ellerbrock, Malte; Haberer, Thomas (Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg (Germany)) (and others)


    The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n = 9) and chondrosarcoma (n = 18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n = 5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n = 3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy-six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients x-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft fuer Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal x-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Dept. of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology.

  17. BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

    Pilar González-Gómez


    Full Text Available Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

  18. Advanced computer-aided intraoperative technologies for information-guided surgical management of gliomas: Tokyo Women's Medical University experience.

    Iseki, H; Nakamura, R; Muragaki, Y; Suzuki, T; Chernov, M; Hori, T; Takakura, K


    The availability of the intraoperative MRI and real-time neuronavigation has dramatically changed the principles of surgery for gliomas. Current intraoperative computer-aided technologies permit perfect localization of the neoplasm, precise estimation of its volume, and clear definition of its interrelationships with the eloquent brain structures. This allows maximal tumor resection with minimal risk of postoperative disabilities. Under such conditions the medical treatment has become significantly dependent on the quality of the provided information and can be designated as information-guided management. Therefore, appropriate management of the wide spectrum of the intraoperative medical data and its adequate distribution between members of the surgical team for facilitation of the clinical decision-making is very important for attainment of the best possible outcome. Further progress in advanced neurovisualization, robotics, and comprehensive medical information technology has a great potential to increase the safety of the neurosurgical procedures for parenchymal brain tumors in the eloquent brain areas.

  19. The Art of Intraoperative Glioma Identification

    Zoe Z Zhang


    Full Text Available A major dilemma in brain tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of 1 image-based navigation, 2 intraoperative sampling, 3 electrophysiological monitoring, and 4 enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease.

  20. The NIF Shear Experiment: Emergent Coherent Structures and Initial Conditions

    Flippo, K. A.; Doss, F. W.; Merritt, E. C.; di Stefano, C. A.; Devolder, B. G.; Kurien, S.; Kot, L.; Loomis, E. N.; Murphy, T. J.; Perry, T. S.; Kline, J. L.; Huntington, C. M.; Nagel, S. R.; MacLaren, S. A.; Schmidt, D. W.


    The NIF Shear experiments are designed to stress turbulence models at high Atwood numbers, high convective Mach number, and in a highly compressible regime. The NIF laser system is used to drive two hohlraums on either end of the experiment, which convert the laser drive into a bath of soft x-rays, 250eV in temperature. The counter-propagating shocks and flow, pressure balance the shear layer, such that it can grow due to the KH instability in the center of the experiment for 20 ns. These experiments are the first High Energy Density (HED) hydro-instability studies to show emergent coherent Kelvin-Helmholtz (KH) structures arising from random broadband seeds, and the first to control the phenomenological evolution of the tracer layer by controlling the initial surface roughness conditions. The change in initial conditions forces the system evolution on a different path that does not appear to reach a universal nor self-similar state by the end of the experiment. The experiment was modeled using the multi-physics hydrodynamic code RAGE with the BHR turbulence model. The initial scale-length of the model is modified to match the data. When the model is turned off, the pure hydrodynamics do not capture the behavior of the mixing layer and cannot match the data.

  1. Epidemiology of gliomas.

    Ostrom, Quinn T; Gittleman, Haley; Stetson, Lindsay; Virk, Selene M; Barnholtz-Sloan, Jill S


    Gliomas are the most common type of primary intracranial tumors. Some glioma subtypes cause significant mortality and morbidity that are disproportionate to their relatively rare incidence. A very small proportion of glioma cases can be attributed to inherited genetic disorders. Many potential risk factors for glioma have been studied to date, but few provide explanation for the number of brain tumors identified. The most significant of these factors includes increased risk due to exposure to ionizing radiation, and decreased risk with history of allergy or atopic disease. The potential effect of exposure to cellular phones has been studied extensively, but the results remain inconclusive. Recent genomic analyses, using the genome-wide association study (GWAS) design, have identified several inherited risk variants that are associated with increased glioma risk. The following chapter provides an overview of the current state of research in the epidemiology of intracranial glioma.

  2. The pathobiology of glioma tumors.

    Gladson, Candece L; Prayson, Richard A; Liu, Wei Michael


    The ongoing characterization of the genetic and epigenetic alterations in the gliomas has already improved the classification of these heterogeneous tumors and enabled the development of rodent models for analysis of the molecular pathways underlying their proliferative and invasive behavior. Effective application of the targeted therapies that are now in development will depend on pathologists' ability to provide accurate information regarding the genetic alterations and the expression of key receptors and ligands in the tumors. Here we review the mechanisms that have been implicated in the pathogenesis of the gliomas and provide examples of the cooperative nature of the pathways involved, which may influence the initial therapeutic response and the potential for development of resistance.

  3. Initial Homosexual Experiences of MSM in Surat City

    Kumar Mukesh, Bansal RK


    Full Text Available This cross-sectional study among 200 Men having sex with men in Surat City explores their initial MSM experiences. Our findings reveal that MSM are sexually active with slightly more bisexual than homosexual. Over half had their first homosexual attraction and relationships before the age of 14 years commonly while playing with friends, though some were forced or raped into their first MSM experience by cousin, friend or elders and care takers. 94% the second homosexual encounter had occurred within 3 months of the first homosexual encounter. These two initial MSM experiences play an important role in future MSM inclinations and highlight the need to ensure that children do not enter into such early relationships before the age of consent. What merits special attention is that these experiences invariably occur during adolescence and their impression makes a lasting effect on their psyche and sexual inclination lifelong. Receptive anal sex emerges as the most common sexual act (89.5% and as the commonest reason for continuing with MSM relationships (26.5%. Friends are the main source (99.5% of entry into an MSM group.

  4. Retrospective Comparison of Chemoradiotherapy Followed by Adjuvant Chemotherapy, With or Without Prior Gliadel Implantation (Carmustine) After Initial Surgery in Patients With Newly Diagnosed High-Grade Gliomas

    Noeel, Georges, E-mail: [Radiation Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Schott, Roland [Medical Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Froelich, Sebastien [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Gaub, Marie-Pierre [Pathology Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Boyer, Patrick; Fischer-Lokou, David [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Dufour, Patrick [Medical Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Kehrli, Pierre; Maitrot, Daniel [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France)


    Purpose: Retrospective study of patients treated for high-grade glioma, with or without biodegradable carmustine wafers and according to the Stupp protocol. Methods and Materials: Between May 2007 and June 2008, 65 patients underwent surgery for high-grade glioma, 28 had implantation of Gliadel and 37 patients did not. Patients received radiotherapy with concomitant temozolomide followed by 5 consecutive days of temozolomide every month for 6 months. Results: Overall median follow-up was 17.1 months; the median relapse-free survival (RFS) was 14 months with a RFS of 54% at 12 months, and 38% at 24 months. For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89). According to pathology, Gliadel did not influence RFS of patients with Grade III or glioblastoma. However, for all patients, in multivariate analysis, non-methylated methylguanine methyltransferase (MGMT) was the only unfavorable prognostic factor of RFS (p = 0.017; HR 2.8; CI [1.2-7]). Median overall survival (OS) was 20.8 months; the OS rate at 12 months was 78.5%, and at 24 months 35.4%. For patients treated with and without Gliadel, median and 1-year OS were 20.6 months and 78.6% vs. 20.8 months and 78.4%, respectively. According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma. For all patients, in multivariate analysis, unfavorable prognosticators for OS were non-methylated MGMT (p = 0.001; HR: 6.5; CI [2-20]) and irradiation dose <60 Gy (p = 0.02; HR: 6.3; CI [2-20]). With carmustine wafers, before irradiation, median gross tumor volume plus edema was 84 mL (27-229), whereas it was 68 mL (10-362) without carmustine (p = nonsignificant). Four cases of Grade 3 thrombopenia occurred, all in the carmustine wafer group. Conclusion: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.

  5. Relapse of herpes encephalitis induced by temozolomide-based chemoradiation in a patient with malignant glioma.

    Okada, Masaki; Miyake, Keisuke; Shinomiya, Aya; Kawai, Nobuyuki; Tamiya, Takashi


    The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

  6. Dynamic crack initiation toughness : experiments and peridynamic modeling.

    Foster, John T.


    This is a dissertation on research conducted studying the dynamic crack initiation toughness of a 4340 steel. Researchers have been conducting experimental testing of dynamic crack initiation toughness, K{sub Ic}, for many years, using many experimental techniques with vastly different trends in the results when reporting K{sub Ic} as a function of loading rate. The dissertation describes a novel experimental technique for measuring K{sub Ic} in metals using the Kolsky bar. The method borrows from improvements made in recent years in traditional Kolsky bar testing by using pulse shaping techniques to ensure a constant loading rate applied to the sample before crack initiation. Dynamic crack initiation measurements were reported on a 4340 steel at two different loading rates. The steel was shown to exhibit a rate dependence, with the recorded values of K{sub Ic} being much higher at the higher loading rate. Using the knowledge of this rate dependence as a motivation in attempting to model the fracture events, a viscoplastic constitutive model was implemented into a peridynamic computational mechanics code. Peridynamics is a newly developed theory in solid mechanics that replaces the classical partial differential equations of motion with integral-differential equations which do not require the existence of spatial derivatives in the displacement field. This allows for the straightforward modeling of unguided crack initiation and growth. To date, peridynamic implementations have used severely restricted constitutive models. This research represents the first implementation of a complex material model and its validation. After showing results comparing deformations to experimental Taylor anvil impact for the viscoplastic material model, a novel failure criterion is introduced to model the dynamic crack initiation toughness experiments. The failure model is based on an energy criterion and uses the K{sub Ic} values recorded experimentally as an input. The failure model

  7. Team learning in medical education: initial experiences at ten institutions.

    Searle, Nancy S; Haidet, Paul; Kelly, P Adam; Schneider, Virginia F; Seidel, Charles L; Richards, Boyd F


    In the midst of curricular reforms that frequently call for reducing lectures and increasing small-group teaching, there is a crisis in faculty time for teaching. This paper describes the initial experiences of ten institutions with team learning (TL), a teaching method which fosters small-group learning in a large-class setting. After initial pilot studies at one institution, nine additional institutions implemented TL in one or more courses. Within 18 months, TL has been used in 40 courses (from.5% to 100% of the time) and all ten institutions will increase its use next year. We surmise that this relatively rapid spread of TL into the medical curriculum is due to the sound pedagogy and efficiency of TL as well as the modest financial resources and support we have provided to partner institutions.

  8. Initiating the development of multisensory integration by manipulating sensory experience.

    Yu, Liping; Rowland, Benjamin A; Stein, Barry E


    The multisensory integration capabilities of superior colliculus neurons emerge gradually during early postnatal life as a consequence of experience with cross-modal stimuli. Without such experience neurons become responsive to multiple sensory modalities but are unable to integrate their inputs. The present study demonstrates that neurons retain sensitivity to cross-modal experience well past the normal developmental period for acquiring multisensory integration capabilities. Experience surprisingly late in life was found to rapidly initiate the development of multisensory integration, even more rapidly than expected based on its normal developmental time course. Furthermore, the requisite experience was acquired by the anesthetized brain and in the absence of any of the stimulus-response contingencies generally associated with learning. The key experiential factor was repeated exposure to the relevant stimuli, and this required that the multiple receptive fields of a multisensory neuron encompassed the cross-modal exposure site. Simple exposure to the individual components of a cross-modal stimulus was ineffective in this regard. Furthermore, once a neuron acquired multisensory integration capabilities at the exposure site, it generalized this experience to other locations, albeit with lowered effectiveness. These observations suggest that the prolonged period during which multisensory integration normally appears is due to developmental factors in neural circuitry in addition to those required for incorporating the statistics of cross-modal events; that neurons learn a multisensory principle based on the specifics of experience and can then apply it to other stimulus conditions; and that the incorporation of this multisensory information does not depend on an alert brain.

  9. Initial clinical experience with Dideco Kids D100 neonatal oxygenator.

    Pace Napoleone, Carlo; Oppido, Guido; Angeli, Emanuela; Shekho, Nazar; De Toni, Erika; Bruzzi, Franco; Gargiulo, Gaetano


    We describe our initial clinical experience with the new hollow fibre membrane oxygenator Dideco Kids D100, used in five patients with a mean age of 21 +/- 28 days. The priming volume is 31 ml with a membrane surface area of 0.22 m2. Data were compared with those deriving from five patients treated with Dideco D901 Lilliput 1 oxygenator. Among patients treated by the new Dideco Kids D100 oxygenator, priming volume was significantly reduced and an easier blood gas delivery was evident.

  10. Initial NIF Shock Timing Experiments: Comparison with Simulation

    Robey, H. F.; Celliers, P. M.; Boehly, T. R.; Datte, P. S.; Bowers, M. W.; Olson, R. E.; Munro, D. H.; Milovich, J. L.; Jones, O. S.; Nikroo, A.; Kroll, J. J.; Horner, J. B.; Hamza, A. V.; Bhandarkar, S. D.; Giraldez, E.; Castro, C.; Gibson, C. R.; Eggert, J. H.; Smith, R. F.; Park, H.-S.; Young, B. K.; Hsing, W. W.; Landen, O. L.; Meyerhofer, D. D.


    Initial experiments are underway to demonstrate the techniques required to tune the shock timing of capsule implosions on the National Ignition Facility (NIF). These experiments use a modified cryogenic hohlraum geometry designed to precisely match the performance of ignition hohlraums. The targets employ a re-entrant Au cone to provide optical access to the shocks as they propagate in the liquid deuterium-filled capsule interior. The strength and timing of the shocks is diagnosed with VISAR (Velocity Interferometer System for Any Reflector) and DANTE. The results of these measurements will be used to set the precision pulse shape for ignition capsule implosions to follow. Experimental results and comparisons with numerical simulation are presented.

  11. Scaffolding Students’ Initial Self-Access Language Centre Experiences

    Robert Croker


    Full Text Available As the number of self-access language centres (SALCs in Japanese universities continues to grow, so too does the challenge of successfully introducing them to first-year university students, whose initial experiences of self-access language learning may otherwise be confusing and even unsettling. One approach is to carefully scaffold students’ first SALC encounters by connecting them with their classroom learning experiences. This paper discusses one such approach developed at a private university in central Japan, which was based upon a two-stage ‘push-pull’ ‘materials-light, people-focused’ strategy. Teachers initially ‘pushed’ their students to visit the SALC by giving them speaking ‘homework’ to be done there. The SALC then also offered interesting interactive events designed to ‘pull’ learners to continue to come. These push-pull activities could be done with few or no materials, and emphasized interaction with people rather than materials. This two-stage, push-pull strategy served as a bridge between the language classroom and a SALC, helping learners make the first steps in their transition from being a ‘classroom English learner’ to becoming a ‘SALC English user’.

  12. Effect of residents' previous laparoscopic surgery experience on initial robotic suturing experience.

    Kilic, Gokhan Sami; Walsh, Teresa M; Borahay, Mostafa; Zeybek, Burak; Wen, Michael; Breitkopf, Daniel


    Objective. To assess the impact of gynecology residents' previous laparoscopic experience on the learning curve of robotic suturing techniques and the value of initial structured teaching in dry lab prior to surgery. Methods. Thirteen gynecology residents with no previous robotic surgery experience were divided into Group 1, consisting of residents with 2 or fewer laparoscopic experiences, and Group 2, consisting of residents with 3 or more laparoscopic experiences. Group 1 had a dry-laboratory training in suturing prior to their initial experience in the operating room. Results. For all residents, it took on average 382 ± 159 seconds for laparoscopic suturing and 326 ± 196 seconds for robotic suturing (P = 0.12). Residents in Group 1 had a lower mean suture time than residents in Group 2 for laparoscopic suturing (P = 0.009). The residents in Group 2, however, had a lower mean suture time on the robot compared to Group 1 (P = 0.5). Conclusion. Residents with previous laparoscopic suturing experience may gain more from a robotic surgery experience than those with limited laparoscopic surgery experience. In addition, dry lab training is more efficient than hands-on training in the initial phase of teaching for both laparoscopic and robotic suturing skills.

  13. [Chemotherapy of chiasmal gliomas in children].

    Helcl, F


    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  14. Morbidity profile following aggressive resection of parietal lobe gliomas.

    Sanai, Nader; Martino, Juan; Berger, Mitchel S


    The impact of parietal lobe gliomas is typically studied in the context of parietal lobe syndromes. However, critical language pathways traverse the parietal lobe and are susceptible during tumor resection. The authors of this study reviewed their experience with parietal gliomas to characterize the impact of resection and the morbidity associated with language. The study population included adults who had undergone resection of parietal gliomas of all grades. Tumor location was identified according to a proposed classification system for parietal region gliomas. Low- and high-grade tumors were volumetrically analyzed using FLAIR and T1-weighted contrast-enhanced MR imaging. One hundred nineteen patients with parietal gliomas were identified--34 with low-grade gliomas and 85 with high-grade gliomas. The median patient age was 45 years, and most patients (53) presented with seizures, whereas only 4 patients had an appreciable parietal lobe syndrome. The median preoperative tumor volume was 31.3 cm(3), the median extent of resection was 96%, and the median postoperative tumor volume was 0.9 cm(3). Surprisingly, the most common early postoperative neurological deficit was dysphasia (16 patients), not weakness (12 patients), sensory deficits (14 patients), or parietal lobe syndrome (10 patients). A proposed parietal glioma classification system, based on surgical anatomy, was predictive of language deficits. This is the largest reported experience with parietal lobe gliomas. The findings suggested that parietal language pathways are compromised at a surprisingly high rate. The proposed parietal glioma classification system is predictive of postoperative morbidity associated with language and can assist with preoperative planning. Taken together, these data emphasize the value of identifying language pathways when operating within the parietal lobe.

  15. Temozolomide in malignant glioma

    Gregor Dresemann


    Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM) is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional ...

  16. PET/MR imaging of atherosclerosis: initial experience and outlook.

    Rischpler, Christoph; Nekolla, Stephan G; Beer, Ambros J


    Hybrid scanners such as PET/CT have in the past emerged as a valuable modality in clinical routine as well as an important research tool. Recently, the newly developed fully integrated PET/MR scanners were introduced to the market, raising high expectations especially due to the excellent soft tissue contrast and functional imaging capabilities of MRI. In this issue of the American Journal of Nuclear Medicine and Molecular Imaging, initial experiences using a hybrid PET/MR scanner for carotid artery imaging in a group of patients with increased risk for atherosclerosis are described. This represents a proof-of-principle study, which could stimulate future applications of this powerful modality in atherosclerotic plaque imaging.

  17. Debris-flow initiation experiments using diverse hydrologic triggers

    Reid, Mark E.; LaHusen, Richard G.; Iverson, Richard M.


    Controlled debris-flow initiation experiments focused on three hydrologic conditions that can trigger slope failure: localized ground-water inflow; prolonged moderate-intensity rainfall; and high-intensity rainfall. Detailed monitoring of slope hydrology and deformation provided exceptionally complete data on conditions preceding and accompanying slope failure and debris-flow mobilization. Ground-water inflow and high-intensity sprinkling led to abrupt, complete failure whereas moderate-intensity sprinkling led to retrogressive, block-by-block failure. Failure during ground-water inflow and during moderate-intensity sprinkling occurred with a rising water table and positive pore pressures. Failure during high-intensity sprinkling occurred without widespread positive pore pressures. In all three cases, pore pressures in most locations increased dramatically (within 2-3 seconds) during failure. In some places, pressures in unsaturated materials rapidly 'flashed' from zero to elevated positive values. Transiently elevated pore pressures and partially liquefied soil enhanced debris-flow mobilization.

  18. Initiation of a thrust fault revealed by analog experiments

    Dotare, Tatsuya; Yamada, Yasuhiro; Adam, Juergen; Hori, Takane; Sakaguchi, Hide


    To reveal in detail the process of initiation of a thrust fault, we conducted analog experiments with dry quartz sand using a high-resolution digital image correlation technique to identify minor shear-strain patterns for every 27 μm of shortening (with an absolute displacement accuracy of 0.5 μm). The experimental results identified a number of "weak shear bands" and minor uplift prior to the initiation of a thrust in cross-section view. The observations suggest that the process is closely linked to the activity of an adjacent existing thrust, and can be divided into three stages. Stage 1 is characterized by a series of abrupt and short-lived weak shear bands at the location where the thrust will subsequently be generated. The area that will eventually be the hanging wall starts to uplift before the fault forms. The shear strain along the existing thrust decreases linearly during this stage. Stage 2 is defined by the generation of the new thrust and active displacements along it, identified by the shear strain along the thrust. The location of the new thrust may be constrained by its back-thrust, generally produced at the foot of the surface slope. The activity of the existing thrust falls to zero once the new thrust is generated, although these two events are not synchronous. Stage 3 of the thrust is characterized by a constant displacement that corresponds to the shortening applied to the model. Similar minor shear bands have been reported in the toe area of the Nankai accretionary prism, SW Japan. By comparing several transects across this subduction margin, we can classify the lateral variations in the structural geometry into the same stages of deformation identified in our experiments. Our findings may also be applied to the evaluation of fracture distributions in thrust belts during unconventional hydrocarbon exploration and production.

  19. Symetis Acurate Neo transfemoral aortic bioprosthesis - initial Polish experience.

    Zembala, Michał; Hawranek, Michał; Wacławski, Jacek; Niklewski, Tomasz; Nadziakiewicz, Paweł; Koba, Rafał; Przybylski, Roman; Walas, Ryszard; Głowacki, Jan; Jazwiec, Tomasz; Garbacz, Marcin; Gąsior, Mariusz; Zembala, Marian


    Transcatheter aortic valve implantation (TAVI) has proven to be a valuable alternative to conventional surgical aortic valve replacement in high-risk and surgically inoperable patients who suffer from severe symptomatic aortic stenosis. With the second generation of TAVI devices improvements in both handling and performance are highly demanded. This brief clinical communication reports the first Polish experience with the second generation of transfemoral TAVI device--Symetis Acurate Neo. From November 19th 2014 until February 18th 2015 nine (n = 9) patients with severe symptomatic aortic stenosis have been operated on using the Symetis Acurate Neo. Patients were subject to seven-day evaluation and 30-day phone follow-up. The procedure was safely and successfully performed in all patients. A SMALL (S) valve (21-23 mm equivalent) was used in two patients, MEDIUM valve (M; 23-25 mm equivalent) in five patients, and a LARGE valve (L; 25-26 mm equivalent) in two patients. In three cases post-release balloon dilatation was required. There were no intraoperative complications and no major adverse events (as per VARC classification) during initial hospitalisation, including conduction or rhythm disturbances. In all cases, the mean gradient on the prosthetic valves was 7.8 mm Hg (10.2 mm Hg on the "S" valves). Rapid improvement in patients' functional class was noted. Perivalvular leak was evaluated as "mild" in three cases, "trace" in one, and "not existing" in five. This initial experience with the Symetis Acurate Neo demonstrates its good safety profile and excellent haemodynamics. Low radial stress of the valve results in minimal incidence of atrioventricular rhythm disturbances, and a sealing crown for nearly non-existent paravalvular leak.

  20. Initial results from the DSPlanar experiments on OMEGA

    Dodd, E. S.; Merritt, E. C.; Montgomery, D. S.; Daughton, W.; Schmidt, D. W.; Cardenas, T.; Wilson, D. C.; Batha, S. H.


    Recently, LANL has begun a project aimed ultimately at fielding a neutron-producing double-shell capsule at the National Ignition Facility (NIF). Initial experiments have begun at both the NIF and OMEGA laser facilities over the last year. At OMEGA, halfraum-driven planar targets will be used to study physics issues important to double shell implosions, but outside of a convergent geometry. In particular, side-on radiography through a tube has advantages over imaging through the hohlraum and double-shell capsule at NIF. We plan to study a number physics issues with this platform, including both 1-d and higher dimensional effects. In 1-d, momentum transfer from the ablator to the inner shell, and the effect of pre-heat on the inner shell can be studied. Higher dimensional effects, in the form of hydrodynamic instabilities, can also be studied. Pre-heat expansion of the inner shell can lead to an unstable interface, which can be mitigated by a tamper layer. Manufacturing tolerances can be used to mitigate against feature-driven instability growth, such as from a glue joint or fill tube. Initial results on the amount pre-heat from various ablator materials will be given, along with a discussion of future plans. Supported under the US DOE by the LANS, LLC under contract DE-AC52-06NA25396. LA-UR-16-25044.

  1. Initially curved microplates under electrostatic actuation: theory and experiment

    Saghir, S.


    Microplates are the building blocks of many micro-electro-mechanical systems. It is common for them to experience initial curvature imperfection due to residual stresses caused by the micro fabrication process. Such plates are essentially different from perfectly flat ones and cannot be modeled using flat plate models. In this paper, we adopt a dynamic analog of the von Karman governing equations of imperfect plates. These equations are then used to develop a reduced order model based on the Galerkin procedure, to simulate the static and dynamic behavior of the microplate under electrostatic actuation. To validate the simulation results, an initially curved imperfect microplate made of silicon nitride is fabricated and tested. The static behaviour of the microplate is investigated when applying a DC voltage Vdc. Then, the dynamic behaviour of the microplate is examined under the application of a harmonic AC voltage, Vac, superimposed to Vdc. The simulation results show good agreement with the experimentally measured responses. © 2016 IOP Publishing Ltd.

  2. CREB1 regulates glucose transport of glioma cell line U87 by targeting GLUT1.

    Chen, Jiaying; Zhang, Can; Mi, Yang; Chen, Fuxue; Du, Dongshu


    Glioma is stemmed from the glial cells in the brain, which is accounted for about 45% of all intracranial tumors. The characteristic of glioma is invasive growth, as well as there is no obvious boundary between normal brain tissue and glioma tissue, so it is difficult to resect completely with worst prognosis. The metabolism of glioma is following the Warburg effect. Previous researches have shown that GLUT1, as a glucose transporter carrier, affected the Warburg effect, but the molecular mechanism is not very clear. CREB1 (cAMP responsive element-binding protein1) is involved in various biological processes, and relevant studies confirmed that CREB1 protein regulated the expression of GLUT1, thus mediating glucose transport in cells. Our experiments mainly reveal that the CREB1 could affect glucose transport in glioma cells by regulating the expression of GLUT1, which controlled the metabolism of glioma and affected the progression of glioma.

  3. Shock initiation experiments on ratchet grown PBX 9502

    Gustavsen, Richard L [Los Alamos National Laboratory; Thompson, Darla G [Los Alamos National Laboratory; Olinger, Barton W [Los Alamos National Laboratory; Deluca, Racci [Los Alamos National Laboratory; Bartram, Brian D [Los Alamos National Laboratory; Pierce, Timothy H [Los Alamos National Laboratory; Sanchez, Nathaniel J [Los Alamos National Laboratory


    This study compares the shock initiation behavior of PBX 9502 pressed to less than nominal density (nominal density is 1.890 {+-} 0.005 g/cm{sup 3}) with PBX 9502 pressed to nominal density and then ''ratchet grown'' to low density. PBX 9502 is an insensitive plastic bonded explosive consisting of 95 weight % dry-aminated tri-amino-tri-nitro-benzene (TATB) and 5 weight % Kel-F 800 plastic binder. ''Ratchet growth'' - an irreversible increase in specific volume - occurs when an explosive based on TATB is temperature cycled. The design of our study is as follows: PBX 9502, all from the same lot, received the following four treatments. Samples in the first group were pressed to less than nominal density. These were not ratchet grown and used as a baseline. Samples in the second group were pressed to nominal density and then ratchet grown by temperature cycling 30 times between -54 C and +80 C. Samples in the final group were pressed to nominal density and cut into 100 mm by 25.4 mm diameter cylinders. During thermal cycling the cylinders were axially constrained by a 100 psi load. Samples for shock initiation experiments were cut perpendicular (disks) and parallel (slabs) to the axial load. The four sample groups can be summarized with the terms pressed low, ratchet grown/no load, axial load/disks, and axial load/slabs. All samples were shock initiated with nearly identical inputs in plate impact experiments carried out on a gas gun. Wave profiles were measured after propagation through 3, 4, 5, and 6 mm of explosive. Side by side comparison of wave profiles from different samples is used as a measure of relative sensitivity. All reduced density samples were more shock sensitive than nominal density PBX 9502. Differences in shock sensitivity between ratchet grown and pressed to low density PBX 9502 were small, but the low density pressings are slightly more sensitive than the ratchet grown samples.

  4. Initial Experience Using the Gore Embolic Filter in Carotid Interventions.

    Hornung, Marius; Franke, Jennifer; Bertog, Stefan C; Gafoor, Sameer; Grunwald, Iris; Sievert, Horst


    This is the first clinical report on experience in the use of the Gore embolic filter in carotid interventions. It was designed as a guidewire and embolic protection system in carotid, peripheral, and coronary interventions. The ability to capture debris is driven by the frame of the filter, which is designed to improve vessel wall apposition and allows a short landing zone. We report the results of the first 20 consecutive patients undergoing carotid artery stenting using the Gore embolic filter in our institution. We analyzed technical success as well as the occurrence of transient ischemic attack (TIA), stroke, or death periprocedurally and through 30 days of follow-up. Mean patient age was 72 years and 12 patients (60%) were male. Seven patients were symptomatic and 4 patients suffered recurrent neurological events. Technical success was achieved in all procedures. In 1 patient, the retrieval catheter was caught between the proximal struts of the stent and required further retrieval maneuvers. Within 30 days of follow-up, 1 patient had a TIA. No stroke, death, or myocardial infarction occurred. This initial experience suggests that the Gore embolic filter device can be used safely for distal embolic protection during carotid stenting procedures with high technical success.

  5. Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience.

    Leuthardt, Eric C


    Awake craniotomy with electrocortical mapping and intraoperative magnetic resonance imaging (iMRI) are established techniques for maximizing tumor resection and preserving function, but there has been little experience combining these methodologies.

  6. [Initial experience in robot-assisted colorectal surgery in Mexico].

    Villanueva-Sáenz, Eduardo; Ramírez-Ramírez, Moisés Marino; Zubieta-O'Farrill, Gregorio; García-Hernández, Luis

    Colorectal surgery has advanced notably since the introduction of the mechanical suture and the minimally invasive approach. Robotic surgery began in order to satisfy the needs of the patient-doctor relationship, and migrated to the area of colorectal surgery. An initial report is presented on the experience of managing colorectal disease using robot-assisted surgery, as well as an analysis of the current role of this platform. A retrospective study was conducted in order to review five patients with colorectal disease operated using a robot-assisted technique over one year in the initial phase of the learning curve. Gender, age, diagnosis and surgical indication, surgery performed, surgical time, conversion, bleeding, post-operative complications, and hospital stay, were analysed and described. A literature review was performed on the role of robotic assisted surgery in colorectal disease and cancer. The study included 5 patients, 3 men and 2 women, with a mean age of 62.2 years. Two of them were low anterior resections with colorectal primary anastomoses, one of them extended with a loop protection ileostomy, a Frykman-Goldberg procedure, and two left hemicolectomies with primary anastomoses. The mean operating time was 6hours and robot-assisted 4hours 20minutes. There were no conversions and the mean hospital stay was 5 days. This technology is currently being used worldwide in different surgical centres because of its advantages that have been clinically demonstrated by various studies. We report the first colorectal surgical cases in Mexico, with promising results. There is enough evidence to support and recommend the use of this technology as a viable and safe option. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  7. Left atrial appendage occlusion: initial experience with the Amplatzer™ Amulet™.

    Freixa, Xavier; Abualsaud, Ali; Chan, Jason; Nosair, Mohamed; Tzikas, Apostolos; Garceau, Patrick; Basmadjian, Arsène; Ibrahim, Réda


    The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated device for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitate the implantation process, improve the sealing performance and further reduce the risk of complications. The objective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAA occlusion. This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. The indication for LAA closure was a formal contraindication for oral anticoagulation or previous history of stroke due to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed 24h after the procedure in order to rule out procedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1-3 months. Between July-2012 and June-2013, 25 patients with a mean CHA2DS2-VASC of 4.3 ± 1.7 underwent LAA occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without any procedural stroke, pericardial effusion or device embolization. None of the patients presented any clinical event at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks >3mm and no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinical expression. In this initial series of patients, the Amulet showed a remarkable acute and short-term performance in terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence of complications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

    Movassaghi, Masoud; Shabihkhani, Maryam; Hojat, Seyed A; Williams, Ryan R; Chung, Lawrance K; Im, Kyuseok; Lucey, Gregory M; Wei, Bowen; Mareninov, Sergey; Wang, Michael W; Ng, Denise W; Tashjian, Randy S; Magaki, Shino; Perez-Rosendahl, Mari; Yang, Isaac; Khanlou, Negar; Vinters, Harry V; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Cloughesy, Timothy F; Yong, William H


    Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to




    Full Text Available Brain stem gliomas/astrocytomas are slowly growing tumors affecting children and young adults. They usually present with unilateral cranial nerve palsies followed by long tract signs. Here we present a case report of a 42 year old male patient, who initially presented with thyrotoxicosis and slowly progressing dysphagia, dysarthria and dysphonia with no other long tract signs, and was later found to have brain stem glioma.

  10. Telomere maintenance and the etiology of adult glioma.

    Walsh, Kyle M; Wiencke, John K; Lachance, Daniel H; Wiemels, Joseph L; Molinaro, Annette M; Eckel-Passow, Jeanette E; Jenkins, Robert B; Wrensch, Margaret R


    A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length.

  11. [Laparoscopic distal gastrectomy for gastric cancer: initial experience].

    Berrospi, Francisco; Celis, Juan; Ruíz, Eloy; Payet, Eduardo; Chávez, Iván; Young, Frank


    To report the initial experience with the laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy for gastric cancer. Between May 2006 and May 2007, 29 consecutive GC patients with gastric cancer underwent LADG with D2 lymphadenectomy. The operation consisted in a laparoscopic time to perform lymphadenectomy and mobilization of the distal stomach, followed by a minilaparotomy for exteriorization of the specimen and construction of a hand sewn anastomosis. Twenty-nine patients underwent LADG with D2 lymphadenectomy for gastric cancer. Mean age was 58.2 years. Mean operative time was 287.4 min. Mean number of lymph nodes resected was 42.6. Twelve patients were early gastric cancer, and seventeen were advanced gastric cancer. Mean proximal and distal resection margin were 5.8 cm and 3.5 cm, respectively. Resection margins were negative in all cases. Mean number of lymph nodes resected was 42.6. Thirty-day morbidity rate was 10.3 %. There were no postoperative deaths.CONCLUSION. The short-term results of our LADG with D2 lymphadenectomy for the treatment of gastric cancer shows that a radical surgery, in terms of resection margins and lymphadenectomy, can be done with low morbidity.

  12. Current status of cerebral glioma surgery in China

    WU Jin-song; ZHANG Jie; ZHUANG Dong-xiao; YAO Cheng-jun; QIU Tian-ming; LU Jun-feng; ZHU Feng-ping; MAO Ying; ZHOU Liang-fu


    The treatment of gliomas is highly individualized.Surgery for gliomas is essentially for histological diagnosis,to alleviate mass effect,and most importantly,to favor longer survival expectancy.During the past two decades,many surgical techniques and adjuvants have been applied to glioma surgery in China,which lead to a rapid development in the field of cerebral glioma surgery.This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China.A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China.The following databases were searched:the Pubmed (January 1995 to date);China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date).A selection criterion was established to exclude duplicates and irrelevant studies.The outcome measures were extracted from included studies.A total of 3307 articles were initially searched.After excluded by abstracts and full texts,69 studies conducted in the mainland of China were included and went through further analysis.The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change.Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients.The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention.The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

  13. Percutaneous MR-guided cryoablation of prostate cancer: initial experience

    Gangi, Afshin; Tsoumakidou, Georgia; Abdelli, Omar; Buy, Xavier [University Hospital of Strasbourg, Department of Interventional Radiology, Strasbourg (France); Mathelin, Michel de [University of Strasbourg, Lsiit, Strasbourg (France); Jacqmin, Didier; Lang, Herve [University Hospital of Strasbourg, Department of Urology, Strasbourg (France)


    We report our initial experience and the technical feasibility of transperineal prostate cryoablation under MR guidance. Percutaneous MR-guided cryoablation was performed in 11 patients with prostatic adenocarcinoma contraindicated for surgery (mean age: 72 years, mean Gleason score: 6.45, mean prostate-specific antigen (PSA): 6.21 ng/ml, T1-2c/N0/M0, mean: prostate volume 36.44 ml). Free-hand probe positioning was performed under real-time MR imaging. Four to seven cryoprobes were inserted into the prostate, depending on gland volume. The ice ball was monitored using real-time and high-resolution BLADE multi-planar imaging. Patients were followed at 1, 3, 6, 9 and 12 months after the procedure with serum PSA level and post-ablation MRI. Prostate cryoablation was technically feasible in 10/11 patients. The ice ball was clearly and sharply visualised in all cases as a signal-void area. Mean ice-ball volume was 53.3 ml. Mean follow-up was 15 months (range: 1-25). Mean PSA nadir was 0.33 ng/ml (range: 0.02-0.94 ng/ml). Mean hospitalisation was 5 days (range: 3-13). Complications included a urethro-rectal fistula, urinary infection, transient dysuria and scrotal pain. MR-guided prostate cryoablation is feasible and promising, with excellent monitoring of the ice ball. Future perspectives could include the use of MR guidance for focal prostate cancer cryotherapy. (orig.)

  14. [The transcatheter closure of patent ductus arteriosus. The initial experience].

    Vázquez-Antona, C A; Rijlaarsdam, M; Gaspar, J; Gil Moreno, M; Buendía Hernández, A; Martínez Ríos, M A; Attie, F


    Percutaneous closure of the patent ductus arteriosus (PDA) has been recently reported to be an effective alternative in the treatment of patients with ductal shunting. We report the initial experience and results during follow-up of percutaneous ductal occlusion with the Rashkind occluder (USCI) in six patients with isolated PDA. Ages ranged from 3 to 23 years. Diagnosis was corroborated with two dimensional and Doppler echocardiography in all patients. During cardiac catheterization systolic pulmonary artery pressure oscillated between 22 and 64 mmHg and Qp/Qs ratio between 1.3 and 4.1. In two patients prosthesis of 12 mm were used and in the remaining prosthesis of 17 mm. Only one patient demonstrated total occlusion during immediate control aortography, the other patients presented central residual shunting over the occluder. In the three patients occlusion with balloon-catheter was added to the procedure, resulting in total occlusion in two and significant reduction of the shunt magnitude in one. Two technical problems were resolved satisfactorily. None of the cases presented device embolization. Mean follow-up was 23.8 months with control echocardiograms at 24 hours, 1, 4, 12 and 24 months. In all patients immediate reduction of the left atrial dimension was demonstrated. Three patients presented residual shunts in the first 24 hours. In two of them total occlusion had occurred after one month and the other patient persisted with a small residual shunt until one year after the procedure. In conclusion, in this small study group good results were obtained with percutaneous ductal closure.

  15. Our initial experience with percutaneous nephrolithotomy in children

    Mehmet Hanifi Okur


    Full Text Available Objective: To present our initial experience on percutaneous nephrolithotomy (PCNL in children between March 2012 and November 2013. Methods: 13 renal units of 12 patients underwent PCNL. Patients were evaluated in terms of age, preoperatively in terms of urine, blood count, urine culture, serum biochemical, and routine coagulation tests and radiological examinations, stone location, stone burden (according to plain radiograph, preoperative use of nephrostomy and average fluoroscopic manipulation time. To facilitate access, prior mechanical dilatation was performed nephrostomy access tract. After the PCNL procedure, we placed nephrostomy in all patients postoperatively. They were evaluated with regard to residual stone, complications (according to the Clavien classification and outcomes. Results: Average age was 11 years (6-15. There was no abnormality in Laboratory Screening. Location of 11 stones was renal pelvis and 2 stones was pelvis + calyx. The average stone size was 260 mm². Preoperative acces were provided in 3 patients, others were intraoperatively. Average fluoroscopic manipulation time was 4,8 minutes (2-11. At the first postoperative day, 11 (85 % patients achieved a completely stone-free state. Complications were seen in 3 patients; failure of renal access in one patient (Grade 3b, urine leakage was observed after surgery in one (Grade 3a, postoperative blood transfusion required in one patient (Grade 2. The hospital stay duration was 5,5 days (5-7 days. Conclusions: Pediatric PCNL is a minimal invasive procedure which provides high rate of stone free and good cosmetics. İf there is adequate facilities and equipment with experienced persons, this procedure can easily be used in pediatric surgery clinics.

  16. Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling.

    a Dzaye, Omar Dildar; Hu, Feng; Derkow, Katja; Haage, Verena; Euskirchen, Philipp; Harms, Christoph; Lehnardt, Seija; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut


    Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive phenotype in these glioma-associated microglia/brain macrophages (GAMs). A subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence-activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs had the capacity to form a tumor of comparable size to the ones formed by 10,000 CD133(-) GL261 cells. In IL-6(-/-) mice, only tumors formed by CD133(+ )cells were smaller compared with wild type. After stimulation of primary cultured microglia with medium from CD133-enriched GL261 glioma cells, we observed an selective upregulation in microglial IL-6 secretion dependent on Toll-like receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells, initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the finding that GAMs are the major source of IL-6 in the tumor context.

  17. The functional role of Notch signaling in human gliomas

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard


    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now......Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  18. Patient and caregiver perceptions of communication of prognosis in high grade glioma.

    Lobb, E A; Halkett, G K B; Nowak, A K


    This study sought the views of patients and their caregivers on their experience of being diagnosed with high grade glioma. Purposive sampling was used to recruit 19 patients and 21 caregivers from the medical oncology unit of a tertiary hospital. A semi-structured face-to-face interview was conducted. Interviews were audio-taped and transcribed verbatim. Data was analysed based on Grounded Theory and using the constant comparison method. This paper focuses on patient and carer perceptions of the initial communication about the diagnosis of high grade glioma and its prognosis. Themes identified included: (a) shock at hearing the diagnosis; (b) trying to understand and process prognostic information when still in shock; (c) the perception of hope being taken away; (d) individualizing prognostic information; and (e) clinicians' lack of communication skills. This study shows that the first communication of prognosis to patients with high grade glioma and their caregivers requires careful negotiation. It illustrates the inability of individuals to process detailed prognostic information when in a state of initial shock and distress. The importance of balancing honesty with hope in the communication of a poor prognosis is highlighted. We recommend that clinicians seek patient preferences for the amount and type of information they require and that prognostic information be individualized. Detailed discussions of prognosis should only take place with senior medical staff, or advanced trainees who have demonstrated acceptable communication skills.

  19. In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model

    Meurer Luise


    Full Text Available Abstract Background ATP is an important signalling molecule in the peripheral and central nervous system. Both glioma growth and tumor resection induces cell death, thus liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed very slowly by gliomas when compared with astrocytes and induce neuronal cell death and glioma proliferation. The objective of the present study was to test the involvement of extracellular ATP in glioblastoma growth in a rat glioma model. Methods To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS. One million glioma C6 cells in 3 microliters of DMEM/FCS were injected in the right striata of male Wistar rats, 250–270 g. After 20 days, the rats were decapitated and the brain sectioning and stained with hematoxylin and eosine. We performed immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with primers for the NTPDase family. Results C6 glioma cells effectively have a low expression of all NTPDases investigated, in comparison with normal astrocytes. The implanted glioma co-injected with apyrase had a significant reduction in the tumor size (p Conclusion These results indicate that the participation of extracellular ATP and the ecto-nucleotidases may be associated with the development of this type of brain tumor in an in vivo glioma model.

  20. Molecular Profiling of Gliomas

    A.M. Gravendeel (Lonneke)


    textabstractGliomas are the most common type of primary brain tumors in adults with an incidence rate of 5.27 per 100.000 patients every year 1-2. In 1926, Bailey and Cushing suggested a classification model based on distinct histological morphologies 3, which forms the basis of the currently used W

  1. Informal Science: Family Education, Experiences, and Initial Interest in Science

    Dabney, Katherine P.; Tai, Robert H.; Scott, Michael R.


    Recent research and public policy have indicated the need for increasing the physical science workforce through development of interest and engagement with informal and formal science, technology, engineering, and mathematics experiences. This study examines the association of family education and physical scientists' informal experiences in…

  2. Professional Experience as a Wicked Problem in Initial Teacher Education

    Southgate, Erica; Reynolds, Ruth; Howley, Peter


    Professional experience in teacher education is explored through the conceptual lens of the wicked problem. Wicked problems are socially constructed and complex. This paper outlines what is at stake in the framing of the problem of professional experience and how constructions of the problem make it difficult to find enduring solutions. The…

  3. Informal Science: Family Education, Experiences, and Initial Interest in Science

    Dabney, Katherine P.; Tai, Robert H.; Scott, Michael R.


    Recent research and public policy have indicated the need for increasing the physical science workforce through development of interest and engagement with informal and formal science, technology, engineering, and mathematics experiences. This study examines the association of family education and physical scientists' informal experiences in…

  4. Neural progenitor and hemopoietic stem cells inhibit the growth of low-differentiated glioma.

    Baklaushev, V P; Grinenko, N F; Savchenko, E A; Bykovskaya, S N; Yusubalieva, G M; Viktorov, I V; Bryukhovetskii, A S; Bryukhovetskii, I S; Chekhonin, V P


    The effects of neural progenitor and hemopoietic stem cells on C6 glioma cells were studied in in vivo and in vitro experiments. Considerable inhibition of proliferation during co-culturing of glioma cells with neural progenitor cells was revealed by quantitative MTT test and bromodeoxyuridine incorporation test. Labeled neural progenitor and hemopoietic stem cells implanted into the focus of experimental cerebral glioma C6 survive in the brain of experimental animals for at least 7 days, migrate with glioma cells, and accumulate in the peritumoral space. Under these conditions, neural progenitor cells differentiate with the formation of long processes. Morphometric analysis of glioma cells showed that implantation of neural progenitor and hemopoietic stem cells is accompanied by considerable inhibition of the growth of experimental glioma C6 in comparison with the control. The mechanisms of tumor-suppressive effects of neural and hemopoietic stem cells require further investigation.

  5. Initial Experiences with Retrieving Similar Objects in Simulation Data

    Cheung, S-C S; Kamath, C


    Comparing the output of a physics simulation with an experiment, referred to as 'code validation,' is often done by visually comparing the two outputs. In order to determine which simulation is a closer match to the experiment, more quantitative measures are needed. In this paper, we describe our early experiences with this problem by considering the slightly simpler problem of finding objects in a image that are similar to a given query object. Focusing on a dataset from a fluid mixing problem, we report on our experiments with different features that are used to represent the objects of interest in the data. These early results indicate that the features must be chosen carefully to correctly represent the query object and the goal of the similarity search.

  6. Diffusion tensor imaging of periventricular leukomalacia – Initial experience

    Eman M. Abdelsalam


    Conclusion: DTI proved to be a promising noninvasive method for assessing the severity of white matter tract injury in patients with PVL. This is owing to the capability of fiber-tracking techniques to provide more information for understanding the pathophysiologic features of sensorimotor and cognitive disability associated with PVL. This will allow for the early intervention and initiation of rehabilitation programs aiming for minimizing the associated neurological deficit.

  7. The Planeterrella experiment: from individual initiative to networking

    Lilensten, Jean; Grimald, Sandrine; Brekke, Asgeir; Fluckiger, Erwin; Vanlommel, Petra; Wedlund, Cyril Simon; Barthélémy, Mathieu; Garnier, Philippe


    Space weather is a relatively new discipline which is generally unknown to the wider public, despite its increasing importance to all of our daily lives. Outreach activities can help in promoting the concept of space weather. In particular the visual beauty and excitement of the aurora make these lights a wonderful inspirational hook. A century ago Norwegian experimental physicist Kristian Birkeland, one of the founding fathers of modern space science, demonstrated with his Terrella experiment the formation of the aurora. Recently a modernised version of the Terrella has been designed. This Planeterrella experiment is very flexible, allowing the visualization of many phenomena occurring in our space environment. Although the Planeterrella was originally designed to be small to be demonstrated locally by a scientist, the Planeterrella has proved to be a very successful public outreach experiment. We believe that its success is due to two main factors (i) the Planeterrella is not patented and the plans are give...

  8. Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

    Andolfi, Laura; Bourkoula, Eugenia; Migliorini, Elisa; Palma, Anita; Pucer, Anja; Skrap, Miran; Scoles, Giacinto; Beltrami, Antonio Paolo; Cesselli, Daniela; Lazzarino, Marco


    Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

  9. Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

    Laura Andolfi

    Full Text Available Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

  10. Human gliomas contain morphine

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei


    morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence....... Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  11. Radiofrequency Ablation for Iatrogenic Thyroid Artery Pseudoaneurysm: Initial Experience.

    Jun, Ye Kyeong; Jung, So Lyung; Byun, Ho Kyun; Baek, Jung Hwan; Sung, Jin Yong; Sim, Jung Suk


    Eight iatrogenic thyroid pseudoaneurysms (ITPAs) after thyroid biopsy are reported. The mean ITPA diameter was 7.2 mm (range 4 to 12 mm). Ultrasound (US)-guided compression was initially performed at the neck of the ITPA in all cases. Among them, 4 ITPAs persisted (50%) in which radiofrequency (RF) ablation was performed. Mean RF ablation time and power were 13.5 seconds (range 5 to 24 seconds) and 20 W (range 10 to 50 W), respectively. All 4 cases were treated with RF ablation without any complications.

  12. Initial operation with sodium in the Madison Dynamo Experiment.

    Kendrick, R.; Spence, Ej; Forest, C. B.; O'Connell, R.; Nornberg, Md; Canary, Hw; Wright, A.; Robinson, K.


    A new liquid metal MHD experiment has been constructed at the University of Wisconsin to test several key predictions of dynamo theory: magnetic instabilities driven by sheared flow, the effects of turbulence on current generation, and the back-reaction of the self-generated magnetic field on the fluid motion which brings saturation. This presentation describes the engineering design of the experiment, which is a 0.5 m radius spherical vessel, filled with liquid sodium at 150 ^circC. The experiment is designed to achieve a magnetic Reynolds number in excess of 100, which requires approximately 80 Hp of mechanical drive, producing flow velocities in sodium of 15 m/s through impellers. Handling liquid sodium offers a number of technical challenges, but routine techniques have been developed over the past several decades for safely handling large quantities for the fast breeder reactor. The handling strategy is discussed, technical details concerning seals and pressurization are presented, and safety elements are highlighted.

  13. Gene expression profiles of gliomas in formalin-fixed paraffin-embedded material

    A.M. Gravendeel (Lonneke); J.J. de Rooi (Johan); P.H.C. Eilers (Paul); M.J. van den Bent (Martin); P.A.E. Sillevis Smitt (Peter); P.J. French (Pim)


    textabstractBackground: We have recently demonstrated that expression profiling is a more accurate and objective method to classify gliomas than histology. Similar to most expression profiling studies, our experiments were performed using fresh frozen (FF) glioma samples whereas most archival sample

  14. Initial experience with ocriplasmin in the treatment of vitreomacular traction

    José Maurício Botto de Barros Garcia


    Full Text Available ABSTRACT This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.

  15. Coherent fluctuations in the initial TFTR D-T experiments

    Fredrickson, E.; Chang, Z.Y.; Budny, R.V.


    The initial operation of TFTR with approximately equal power in the tritium and deuterium neutral beam injectors has resulted in the production of fusion power in excess of 9MW and central {beta}{sub {alpha}} > 0.25%. This {beta}{sub {alpha}} is within a factor of 2--3 of the {beta}{sub {alpha}} in projections of ITER performance. Effects of this {alpha} population on TAE modes, sawteeth and fishbone activity are being searched for. The D-T plasmas are also being studied for evidence of changes in MHD activity which might be attributed to the fast {alpha} population. This paper reports on the activity in the Alfven range of frequencies in the D-T plasmas and on detailed measurements of the MHD activity preceding major disruptions in D-D and D-T.

  16. Cardiac biplane strain imaging: initial in vivo experience

    Lopata, R G P; Nillesen, M M; Thijssen, J M; De Korte, C L [Clinical Physics Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Verrijp, C N; Lammens, M M Y; Van der Laak, J A W M [Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Singh, S K; Van Wetten, H B [Department of Cardiothoracic Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Kapusta, L [Pediatric Cardiology, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)], E-mail:


    In this study, first we propose a biplane strain imaging method using a commercial ultrasound system, yielding estimation of the strain in three orthogonal directions. Secondly, an animal model of a child's heart was introduced that is suitable to simulate congenital heart disease and was used to test the method in vivo. The proposed approach can serve as a framework to monitor the development of cardiac hypertrophy and fibrosis. A 2D strain estimation technique using radio frequency (RF) ultrasound data was applied. Biplane image acquisition was performed at a relatively low frame rate (<100 Hz) using a commercial platform with an RF interface. For testing the method in vivo, biplane image sequences of the heart were recorded during the cardiac cycle in four dogs with an aortic stenosis. Initial results reveal the feasibility of measuring large radial, circumferential and longitudinal cumulative strain (up to 70%) at a frame rate of 100 Hz. Mean radial strain curves of a manually segmented region-of-interest in the infero-lateral wall show excellent correlation between the measured strain curves acquired in two perpendicular planes. Furthermore, the results show the feasibility and reproducibility of assessing radial, circumferential and longitudinal strains simultaneously. In this preliminary study, three beagles developed an elevated pressure gradient over the aortic valve ({delta}p: 100-200 mmHg) and myocardial hypertrophy. One dog did not develop any sign of hypertrophy ({delta}p = 20 mmHg). Initial strain (rate) results showed that the maximum strain (rate) decreased with increasing valvular stenosis (-50%), which is in accordance with previous studies. Histological findings corroborated these results and showed an increase in fibrotic tissue for the hearts with larger pressure gradients (100, 200 mmHg), as well as lower strain and strain rate values.

  17. Cardiac biplane strain imaging: initial in vivo experience

    Lopata, R. G. P.; Nillesen, M. M.; Verrijp, C. N.; Singh, S. K.; Lammens, M. M. Y.; van der Laak, J. A. W. M.; van Wetten, H. B.; Thijssen, J. M.; Kapusta, L.; de Korte, C. L.


    In this study, first we propose a biplane strain imaging method using a commercial ultrasound system, yielding estimation of the strain in three orthogonal directions. Secondly, an animal model of a child's heart was introduced that is suitable to simulate congenital heart disease and was used to test the method in vivo. The proposed approach can serve as a framework to monitor the development of cardiac hypertrophy and fibrosis. A 2D strain estimation technique using radio frequency (RF) ultrasound data was applied. Biplane image acquisition was performed at a relatively low frame rate (cardiac cycle in four dogs with an aortic stenosis. Initial results reveal the feasibility of measuring large radial, circumferential and longitudinal cumulative strain (up to 70%) at a frame rate of 100 Hz. Mean radial strain curves of a manually segmented region-of-interest in the infero-lateral wall show excellent correlation between the measured strain curves acquired in two perpendicular planes. Furthermore, the results show the feasibility and reproducibility of assessing radial, circumferential and longitudinal strains simultaneously. In this preliminary study, three beagles developed an elevated pressure gradient over the aortic valve (Δp: 100-200 mmHg) and myocardial hypertrophy. One dog did not develop any sign of hypertrophy (Δp = 20 mmHg). Initial strain (rate) results showed that the maximum strain (rate) decreased with increasing valvular stenosis (-50%), which is in accordance with previous studies. Histological findings corroborated these results and showed an increase in fibrotic tissue for the hearts with larger pressure gradients (100, 200 mmHg), as well as lower strain and strain rate values.

  18. Management support to e-business initiatives: The Croatian experience

    Mario Spremić


    Full Text Available After defining e-business and explaining why an evolutionary aspect of moving to e-business is required, the dimensions of e-business is defined with respect to differences between traditional business, partial, or pure e-business. Also, a model for moving to e-business is illustrated. The e-business evolving model is divided into six stages and represents an evolutionary aspect of migrating to e-business. Finally, the results of the research study on current practices in evolving e-business in the most successful Croatian companies are given. In this research, some aspects of business process innovation and e-business usage have been investigated (general e-business issues with levels of e-business usage, key objectives of participating in e-business, alignment of business strategy with e-business initiatives, initiation of e-business projects and e-business planning issues, especially e-business funding. The questionnaire was sent to 400 CEOs or CIOs in Croatian companies selected from the Register of the ‘400 Biggest’ Croatian companies which were ranked according to their 2001 annual revenue and which were most likely to represent the structure of the Croatian economy. Although they represent less than 1% of the total number of registered companies in Croatia, the sampled companies hold 73% of the equity capital of the whole Croatian economy, they contribute with 65% in the total Croatian economy’s export balance and they employ 37% of the total number of people employed in Croatia.

  19. The Planeterrella experiment: from individual initiative to networking

    Garnier Pierre


    Full Text Available Space weather is a relatively new discipline, which is still largely unknown amongst the wider public despite its increasing importance in all of our daily lives. Outreach activities can promote awareness of space weather. In particular the visual beauty and excitement of the aurora make these lights a wonderful inspirational hook to enhance understanding of space weather in a general audience. A century ago, the Norwegian experimental physicist Kristian Birkeland, one of the founding fathers of modern space science, demonstrated with his Terrella experiment the formation of the aurora. Recently, a modernized version of the Terrella has been designed. This “Planeterrella” experiment allows the visualization of many phenomena that occur in our space environment. Although the Planeterrella was originally a local project, it has developed to become a very successful international public outreach experiment. We believe that its success is due to mainly two factors (i the Planeterrella is not patented and the plans are free to any public institute and (ii the project is widely advertised using national and European scientific networks such as COST ES 0803, as well as press releases, books and web sites. Today, seven Planeterrellas are in operation, four more are under construction in four different countries and several more are being planned. During the last five years, about 50 000 people in Europe have attended live Planeterrella demonstration on the formation of auroral light, the space environment and space weather. Many more have seen the Planeterrella being demonstrated on TV. The Planeterrella received the first international prize for outreach activities from the Europlanet Framework 7 program in 2010 and the French Ministry of Science outreach prize “Le goût des sciences” in November 2012. This paper describes the process that led to the construction of the first Planeterrella and discusses how the Planeterrella project developed

  20. The Planeterrella experiment: from individual initiative to networking

    Lilensten, J.; Provan, G.; Barthelemy, M.; Simon Wedlund, C.; Gronoff, G.; Vanlommel, P.; Brekke, A.; Garnier, P.; Grimald Rochel, S.


    Space weather is a relatively new discipline, which is still largely unknown amongst the wider public despite its increasing importance in all of our daily lives. Outreach activities can promote awareness of space weather. In particular the visual beauty and excitement of the aurora make these lights a wonderful inspirational hook to enhance understanding of space weather in a general audience. A century ago, the Norwegian experimental physicist Kristian Birkeland, one of the founding fathers of modern space science, demonstrated with his Terrella experiment the formation of the aurora. Recently, a modernized version of the Terrella has been designed in France. This ';';Planeterrella'' experiment allows the visualization of many phenomena that occur in our space environment. Although the Planeterrella was originally a local project, it has developed to become a very successful international public outreach experiment. We believe that its success is due to mainly two factors (i) the Planeterrella is not patented and the plans are free to any public institute and (ii) the project is widely advertised using national and scientific networks, as well as press releases, books and web sites. Today, nine Planeterrellas are in operation, six more are under construction in five different countries including in the US and several more are being planned. During the last five years, about 55 000 people in Europe have attended live Planeterrella demonstration on the formation of auroral light, the space environment and space weather. Many more have seen the Planeterrella being demonstrated on TV. It is now used for education, outreach, scientific, and artistic purposes. We will describes this process and discuss how the Planeterrella project developed to become an international public outreach phenomenon. We also examine some of the lessons learnt along the way such as patented or not, big or small, automatized or hand-operated, and the cost of the overall project. A star (close

  1. Operational experience during initial beam commissioning of the LHC

    Fuchsberger, K; Arduini, G; Assmann, R; Bailey, R; Bruning, O; Goddard, B; Kain, V; Lamont, M; MacPherson, A; Meddahi, M; Papotti, G; Pojer, M; Ponce, L; Redaelli, S; Solfaroli Camillocci, M; Venturini Delsolaro, W; Wenninger, J


    After the incident on the 19th September 2008 and more than one year without beam the commissioning of the LHC started again on November 20, 2009. Progress was rapid and collisions under stable beam conditions were established at 1.2 TeV within 3 weeks. In 2010 after qualification of the new quench protection system the way to 3.5 TeV was open and collision were delivered at this energy after a month of additional commissioning. This paper describes the experiences and issues encountered during these first periods of commissioning with beam.

  2. Robotic-assisted partial Nephrectomy: initial experience in South America

    Gustavo C. Lemos


    Full Text Available OBJECTIVE:To report the initial outcomes of robotic-assisted partial nephrectomy in a tertiary center in South America. MATERIAL AND METHODS: From 11/2008 to 12/2009, a total of 16 transperitoneal robotic-assisted partial nephrectomies were performed in 15 patients to treat 18 kidney tumors. One patient with bilateral tumor had two procedures, while two patients with two synchronous unilateral tumors had a single operation to remove them. Eleven (73% patients were male and the right kidney was affected in 7 (46% patients. The median patient age and tumor size were 57 years old and 30 mm, respectively. Five (28% tumors were hilar and/or centrally located. RESULTS: The median operative time, warm ischemia time and estimated blood loss was 140 min, 27 min and 120 mL, respectively. Blood transfusion was required in one patient with bilateral tumor, and one additional pyelolithotomy was performed due to a 15mm stone located in the renal pelvis. The histopathology analysis showed 15 (83% malignant tumors, which 10 (67% were clear cell carcinoma. The median hospital stay was 72 hrs and no major complication was observed. CONCLUSION: Robotic-assisted partial nephrectomy is safe and represents a valuable option to perform minimally invasive nephron-sparing surgery.

  3. Initial experience with tadalafil in pediatric pulmonary arterial hypertension.

    Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar


    This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.

  4. Initial Active MHD Spectroscopy Experiments on Alcator C-MOD

    Schmittdiel, D. A.; Snipes, J. A.; Granetz, R. S.; Parker, R. R.; Wolfe, S. M.; Fasoli, A.


    The Active MHD Spectroscopy system is a new diagnostic on C-MOD that will be used to study low frequency MHD modes and TAE's present at high B_tor, n_e, and Te ˜= T_i. The present system consists of two antennas, power amplifiers, and an impedance matching network. Each antenna is 15 × 25 cm with five turns, an inductance of ˜10 μH, and is covered by boron nitride tiles. The two antennas are placed at the same toroidal location, symmetrically above and below the midplane. Each antenna is driven by a ˜1 kW power amplifier in the range of 1 kHz - 1 MHz with an expected antenna current ˜10 A, which will produce a vacuum field of ˜0.5 G at the q = 1.5 surface. This diagnostic is designed to excite high n ( ˜20) stable TAE's and initial results regarding their frequency, mode structure, and damping rate will be presented. Evolution of these modes could also provide information on the q profile to compare with MSE measurements, which will be important for planned lower hybrid current drive operation in 2003.

  5. Initial Diagnostics for the National Spherical Torus Experiment

    A.L. Roquemore; B. McCormack; D. Johnson; H. Kugel; R. Kaita; and the NSTX Team


    The spherical torus (ST) approach to magnetic confinement has many attractive features as both a fusion reactor concept and a volume neutron source. The National Spherical Torus Experiment (NSTX) is under construction at the Princeton Plasma Physics Laboratory (PPPL), and it is designed to achieve plasma parameters needed for a proof-of-principle test of the ST concept. Discharges with magnetic fields of 2.3 kG on axis and plasma currents of 1 MA will be heated with 6 MW of radio frequency (RF) power and 5 MW of neutral beams, and pulse lengths up to 5 seconds are planned. Central electron temperatures of about 4 keV are expected with RF heating, and theoretical studies show that high values of b and b{sub n} can be achieved.

  6. Proteomic data analysis of glioma cancer stem-cell lines based on novel nonlinear dimensional data reduction techniques

    Lespinats, Sylvain; Pinker-Domenig, Katja; Wengert, Georg; Houben, Ivo; Lobbes, Marc; Stadlbauer, Andreas; Meyer-Bäse, Anke


    Glioma-derived cancer stem cells (GSCs) are tumor-initiating cells and may be refractory to radiation and chemotherapy and thus have important implications for tumor biology and therapeutics. The analysis and interpretation of large proteomic data sets requires the development of new data mining and visualization approaches. Traditional techniques are insufficient to interpret and visualize these resulting experimental data. The emphasis of this paper lies in the application of novel approaches for the visualization, clustering and projection representation to unveil hidden data structures relevant for the accurate interpretation of biological experiments. These qualitative and quantitative methods are applied to the proteomic analysis of data sets derived from the GSCs. The achieved clustering and visualization results provide a more detailed insight into the protein-level fold changes and putative upstream regulators for the GSCs. However the extracted molecular information is insufficient in classifying GSCs and paving the pathway to an improved therapeutics of the heterogeneous glioma.

  7. PET/MRI in head and neck cancer: initial experience

    Platzek, Ivan; Laniado, Michael [Dresden University Hospital, Department of Radiology, Dresden (Germany); Beuthien-Baumann, Bettina [Dresden University Hospital, Department of Nuclear Medicine, Dresden (Germany); Schneider, Matthias [Dresden University Hospital, Oral and Maxillofacial Surgery, Dresden (Germany); Gudziol, Volker [Dresden University Hospital, Department of Otolaryngology, Dresden (Germany); Langner, Jens; Schramm, Georg; Hoff, Joerg van den [Institute of Bioinorganic and Radiopharmaceutical Chemistry, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Kotzerke, Joerg [Dresden University Hospital, Nuclear Medicine, Dresden (Germany)


    To evaluate the feasibility of PET/MRI (positron emission tomography/magnetic resonance imaging) with FDG ({sup 18}F-fluorodeoxyglucose) for initial staging of head and neck cancer. The study group comprised 20 patients (16 men, 4 women) aged between 52 and 81 years (median 64 years) with histologically proven squamous cell carcinoma of the head and neck region. The patients underwent a PET scan on a conventional scanner and a subsequent PET/MRI examination on a whole-body hybrid system. FDG was administered intravenously prior to the conventional PET scan (267-395 MBq FDG, 348 MBq on average). The maximum standardized uptake values (SUV{sub max}) of the tumour and of both cerebellar hemispheres were determined for both PET datasets. The numbers of lymph nodes with increased FDG uptake were compared between the two PET datasets. No MRI-induced artefacts where observed in the PET images. The tumour was detected by PET/MRI in 17 of the 20 patients, by PET in 16 and by MRI in 14. The PET/MRI examination yielded significantly higher SUV{sub max} than the conventional PET scanner for both the tumour (p < 0.0001) and the cerebellum (p = 0.0009). The number of lymph nodes with increased FDG uptake detected using the PET dataset from the PET/MRI system was significantly higher the number detected by the stand-alone PET system (64 vs. 39, p = 0.001). The current study demonstrated that PET/MRI of the whole head and neck region is feasible with a whole-body PET/MRI system without impairment of PET or MR image quality. (orig.)

  8. Application of robotics in general surgery: initial experience.

    Nguyen, Ninh T; Hinojosa, Marcelo W; Finley, David; Stevens, Melinda; Paya, Mahbod


    Robotic surgery was recently approved for clinical use in general abdominal surgery. The aim of this study was to review our experience with the da Vinci surgical system during laparoscopic general surgical procedures. Eighteen patients underwent robotically assisted laparoscopic abdominal surgery between June 2002 and March 2003. Main outcome measures were operative time, room setup time, robotic arm-positioning and surgical time, blood loss, conversion to laparoscopy, length of stay, and morbidity. The types of robotically assisted laparoscopic procedures were excision of gastric leiomyoma (n = 1), Heller myotomy (n = 1), cholecystectomy (n = 2), gastric banding (n = 2), Nissen fundoplication (n = 4), and gastric bypass (n = 8). The mean room setup time was 63 +/- 14 minutes, and the mean robotic arm-positioning time was 16 +/- 7 minutes. Conversion to laparoscopy occurred in two (11%) of 18 cases because of equipment difficulty (n = 1) and technical difficulty (n = 1). Estimated blood loss was 91 +/- 71 mL. The mean operative time was 156 +/- 42 minutes, and the robotic operative time was 27% of the total operative time. The mean length of hospital stay was 2.2 +/- 1.5 days. There was one postoperative wound infection and one anastomotic stricture. Robotically assisted laparoscopic abdominal surgery is feasible and safe; however, the theoretical advantages of the da Vinci surgical system were not clinically apparent.

  9. The role of psychological support in cardiac surgery: initial experience

    Fabrizio Sansone


    Full Text Available The scientific literature has pointed out several predictors of negative outcome after surgery such as pain and depression, negatively affecting the postoperative outcome in cardiac surgery. From January 2009 until June 2010, 15 patients scheduled for cardiac surgery were enrolled. The patients were assessed by psychological evaluation either in the hospital stay either in the rehabilitation period with the aim of identifying their emotional condition (sentiments about the onset of the disease, support received from family and friends even by means of preformed tests for anxiety and depression (tests of Stay and Back. Thus, in our preliminary experience, the psychological evaluation failed to detect the occurrence of postoperative complications. Conversely, the psychological evaluation is very effective in detecting a poor emotional state and the psychological support decreases the degree of anxiety and depression with positive effects on postoperative outcome. In conclusion, a standardize test for anxiety and depression should be used for patients at hospital admission to detect who may benefits by psychological support.

  10. Initial experience with a nuclear medicine viewing workstation

    Witt, Robert M.; Burt, Robert W.


    Graphical User Interfaced (GUI) workstations are now available from commercial vendors. We recently installed a GUI workstation in our nuclear medicine reading room for exclusive use of staff and resident physicians. The system is built upon a Macintosh platform and has been available as a DELTAmanager from MedImage and more recently as an ICON V from Siemens Medical Systems. The workstation provides only display functions and connects to our existing nuclear medicine imaging system via ethernet. The system has some processing capabilities to create oblique, sagittal and coronal views from transverse tomographic views. Hard copy output is via a screen save device and a thermal color printer. The DELTAmanager replaced a MicroDELTA workstation which had both process and view functions. The mouse activated GUI has made remarkable changes to physicians'' use of the nuclear medicine viewing system. Training time to view and review studies has been reduced from hours to about 30-minutes. Generation of oblique views and display of brain and heart tomographic studies has been reduced from about 30-minutes of technician''s time to about 5-minutes of physician''s time. Overall operator functionality has been increased so that resident physicians with little prior computer experience can access all images on the image server and display pertinent patient images when consulting with other staff.

  11. Initial experience with a newly developed cementless hip endoprosthesis.

    Hach, V; Delfs, G


    The HELICA-Endoprosthesis is a newly developed cementless hip prosthesis for dogs. It was implanted in 39 dogs that had severe hip osteoarthritis and a history of hip pain, as well as in one dog that had chronic hip luxation. One dog had a bilateral arthroplasty. The body weight of the patients ranged between 22 and 54 kg and their ages between nine months and 10 years. Both the femoral stem and acetabular component of the prosthesis were screwed into position following bony preparation. Additional fixation was not necessary as the components remain fixed in position until osteointegration is complete. There are currently five sizes of prosthesis available, and the various components such as the stem, cup and head are readily interchangeable. Although it appeared that good osseous anchorage of the prostheses in the bone on the surgery table had been obtained, three patients experienced both stem and cup loosening (one week, three weeks and six months after surgery). In one animal, stem loosening was observed six weeks after surgery, and another dog experienced a cup loosening two weeks postoperatively. Most of the complications were due to technical errors that occurred during the learning phase. Surgical revisions were successful in three out of five animals. In two animals we had to perform a femoral head and neck excision. Two other animals experienced radiographic bone resorption underneath the segmented collar of the femoral prosthesis but did not show any significant clinical signs of lameness. Another dog that showed signs of ischial neuropraxy after surgery, recovered completely within six weeks after surgery. All of the dogs were capable of weight bearing on the operated leg one day after surgery. The main advantage of the HELICA-Endoprosthesis is the relatively easy surgical technique and short surgery time. The initial clinical results in these 40 cases have been very encouraging. The aim of this study was to assess the early clinical results in these 39

  12. Laparoscopic colorectal surgery: what to expect from an initial experience

    Fábio Ramos Teixeira


    Full Text Available Laparoscopic colorectal surgery is less traumatic when compared to traditional surgery techniques, with well-established advantages. The objective of this study was to report the experience in laparoscopic surgical treatment of colorectal diseases. METHOD: Catalog all patients submitted to laparoscopic colorectal surgery performed by one surgeon and perform a descriptive analysis of key data from these records. RESULTS: The study analyzed data from 43 patients who underwent laparoscopic colorectal surgery. Most were females (n=30; 69.77% in relation to males (n=13; 30.23%, mean age of 57.21 years old. Among the indications for surgery, diverticular disease was the most frequent (n=20; 46.51%, followed by malignancy (n=13; 30.23%. Most patients underwent rectosigmoidectomy (n=28; 65.12%, followed by right hemicolectomy (n=6; 13.95%, with conversions in five cases (11.63%. The study observed a tendency towards increased number of surgeries, reduced average operative time as well as decreased conversions to laparotomy along the studied period. CONCLUSION: Laparoscopic colorectal surgery is a safe procedure, and with the technical development of the team, the results have been increasingly good.A videolaparoscopia colorretal apresenta-se como uma tática operatória menos traumática com vantagens bem-estabelecidas. O objetivo deste trabalho foi apresentar a experiência no tratamento cirúrgico videolaparoscópico das afecções colorretais. MÉTODO: Catalogar todos os pacientes submetidos à cirurgia colorretal videolaparoscópica realizadas por um único cirurgião e realizar uma análise descritiva dos principais dados a partir dos prontuários destes. RESULTADOS: O estudo analisou dados de 43 pacientes que foram submetidos à cirurgia colorretal por videolaparoscopia. A maioria era do gênero feminino (n=30; 69,77% em relação ao masculino (n=13; 30,23% com média de idade de 57,21 anos. Dentre as indicações cirúrgicas, doença diverticular


    Zhu-hua Zhang; Wen-min Zhao; Wen-bin Mou; Li-ren Zhang; Wen-ling Zhu; Qi Miao; Qi Fang; Zheng-yu Jin; Shu-yang Zhang; Song-bai Lin; Dong-jing Li; Ling-yan Kong; Yi-ning Wang; Lan Song; Yun Wang


    To explore the scan technique and image quality of coronary angiography with dual source computed tomography (CT) without oral metoprolol preparation.Methods Plain and enhanced dual source CT coronary angiography without oral metoprolol preparation was prospectively performed in 600 patients. Calcium scoring with plain scan images as well as multi-planar reconstruction( MPR ), maximum intensity projection (MIP), and volume rendering technique (VRT) reconstruction with enhanced scan images were performed in all cases. The scan technique and post-reconstruction experience was summarized. The image quality was classified as 1 to 4 points, and coronary segments classified according to the American Heart Association standards were evaluated.Results The average calcium score of the 600 cases was 213.6 ± 298.7 (0-3 216. 5). The average heart rate of the enhanced scan was 82.1 ± 16.2 (47-139) bpm. The post-reconstruction methods with which coronary segments could be shown as best as possible consisted of single phase reconstruction method, two or more phases supplemented method, and electrocardiogram editing method. Altogether 8 457 coronary segments were evaluated, among which 97.2% were evaluated as point 1, 1.7% point 2, 0.5% point 3, and0.6% point 4. The coronary segments in 261 cases were completely normal, while 360 segments were diagnosed with < 50% stenosis and 625 segments with ≥50%stenosis.Conclusions Excellent coronary artery image can be obtained with dual source CT in patients with any heart rate without oral metoprolol preparation. Heart rate is not a major source of the artifact, coronary segments can be well shown with single or multiple-phase reconstruction method.

  14. Glioma supratentorial de baixo grau em adulto: experiência com 23 pacientes operados Supratentorial low grade tumors in adults: an experience with 23 surgical cases

    José Carlos Lynch


    Full Text Available Os astrocitomas e oligodendrogliomas supratentoriais dos adultos são tumores infrequentes. Analisamos retrospectivamente 23 pacientes com este tipo de neoplasia que foram operados entre 1986 e 2002. Não ocorreu nenhum óbito no pós-operatório. A sobrevida de 5 e 10 anos de todo o grupo foi 67 e 30% respectivamente, semelhante a outras experiências. Em 14 pacientes obtivemos a remoção completa da lesão (60,8% e em 9 (39,2% ocorreu remoção parcial do tumor. No subgrupo da ressecção total do tumor, 89% sobreviveram 5 anos e 45% alcançaram 10 anos de sobrevida, em contraste com o subgrupo da remoção parcial em que somente 35% alcançaram os 5 anos de sobrevida e nenhum, 10 anos. Devido aos efeitos deletérios da radioterapia, nós preferimos prescrevê-la apenas nos casos de recorrência tumoral.Low-grade supratentorial astrocytomas and oligodendrogliomas in adults are uncommon tumors of the central nervous system. We analyzed retrospectively 23 patients with this type of neoplasia, who were operated on between 1986 and 2002. There were no post-operative deaths. The survival rate at 5 and 10 years post-surgery for the entire sample was 67 and 30% respectively, similar to other outcomes. With 14 patients we achieved a complete removal of the lesion (60.8% and with 9 (39.2% partial removal of the tumor. In the sub-group which underwent total resection of the tumor, 89% survived 5 years and 45% attained 10 years of survival, in contrast with the sub-group that underwent partial removal in which only 35% attained 5 years of survival and none 10 years. Due to the deleterious effects of radiation therapy, we preferred to prescribe it only in cases of tumor recurrence.

  15. Digital breast tomosynthesis (DBT): initial experience in a clinical setting

    Skaane, Per; Gullien, Randi; Eben, Ellen B.; Haakenaasen, Unni; Naess Jebsen, Ingvild; Krager, Mona [Dept of Radiology, Oslo Univ. Hospital Ullevaal, Univ. of Oslo, Oslo (Norway)], e-mail:; Bjoerndal, Hilde [Dept of Radiology, Oslo Univ. Hospital The Norwegian Radium Hospital, Oslo (Norway); Ekseth, Ulrika [Curato Roentgen Institute, Oslo (Norway); Jahr, Gunnar [Dept. of Radiology, Oslo Univ. Hospital Rikshospitalet, Oslo (Norway)


    false-positive findings. The side-by-side feature analysis showed higher conspicuity scores for tomosynthesis compared to conventional 2D for cancers presenting as spiculated masses and distortions. Conclusion: Tomosynthesis is a promising new technique. Our preliminary clinical experience shows that there is a potential for increasing the sensitivity using this new technique, especially for cancers manifesting as spiculated masses and distortions.

  16. Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance.

    Shahi, M H; Farheen, S; Mariyath, M P M; Castresana, J S


    Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide.

  17. Temozolomide in malignant glioma

    Gregor Dresemann


    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma

  18. Dynamic radiological change of gliomas located in the paralimbic system and its clinical significance

    CHEN Xu-zhu; JIANG Tao; LI Shao-wu; AI Lin; DAI Jian-ping


    Background The paralimbic system, which is composed of three parts, is an important functional unit. Gliomas located in the region remain a challenge for clinical treatment. However, the dynamic change of gliomas in the area has not been well documented. The purpose of this study was to identify the growth tendency of gliomas located in the paralimbic system and to obtain some suggestions for clinical treatment. Methods Eleven cases of gliomas located in the paralimbic system were recruited in the study. All of them were proven by pathology. Analysis of the serial radiological examinations in each patient was performed from the initial to the final examination, taking into consideration the following items: initial tumor location, final location and the growth tendency. Results In the initial and final examinations the ratios of insula involvement were 64% and 100%, respectively. On the other hand, the ratios of gliomas located in two or more partS of paralimbic system increased from 64%to 100%during the dynamic examination. Conclusions Even though the paralimbic system is composed of three independent anatomical parts, gliomas tend to involve all three pans, especially the insula. Therapeutic plans should aim at the whole region of the system, even during the early stages of gliomas.

  19. Tricyclic Neovibsanin Scaffold Inhibits Glioma by Targeting Glioma ...

    formation capacity and induction of apoptosis in glioma cells. Methods: ... present in plants and possess polyfunctional structures ... the ethics and review committee for the animal studies at .... adhered and started to differentiate forming U138.

  20. Epo is involved in angiogenesis in human glioma.

    Nico, Beatrice; Annese, Tiziana; Guidolin, Diego; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico


    In this study, the extent of angiogenesis, evaluated as microvascular density, and the immunoreactivity of tumor cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human glioma specimens, and the effect of anti-Epo antibody on glioma-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane (CAM) has been investigated. Results show that: (1) Epo/EpoR expression correlates with angiogenesis, (2) in the CAM assay, tumor bioptic specimens induce a strong angiogenic response, comparable to that induced by VEGF, and (3) an anti-Epo antibody co-administered with tumor bioptic specimens significantly inhibits the angiogenic response. These findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by glioma tumor cells and it affects glioma vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner. Moreover, as demonstrated by in vivo experiments, Epo is responsible for the strong angiogenic response induced by human glioma bioptic specimens, because an anti-Epo antibody is able to significantly inhibit this response.

  1. Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process.

    Galvao, Rui Pedro; Kasina, Anita; McNeill, Robert S; Harbin, Jordan E; Foreman, Oded; Verhaak, Roel G W; Nishiyama, Akiko; Miller, C Ryan; Zong, Hui


    How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.

  2. [Controversy on treatments for gliomas].

    Nomura, K


    Gliomas are representative primary malignant brain tumors, and with such tumors it is difficult to define the advanced stage. If the advanced stage indicates no curability by surgery alone, most gliomas would belong to this criterion because of their poor prognosis without any completely effective treatment. In this sense, no one could show a standard therapy to treat these unfortunate patients, for example, patients with glioblastoma, they could permit only 1 year survived even they had any applicable treatments to the lesions, these days. Treatment for low-grade gliomas has been most controversial for a long time, and no standard treatments have been determined so far. In this paper, as the treatment of low-grade gliomas it was intended to report what must be done for this patient and the present results of opinion survey for the treatment of gliomas which was done to professors of 80 institutes, from schools of medicine at all universities and medical colleges in Japan. For high-grade gliomas, some effectiveness of radiation therapy was disclosed as well as chemotherapy from recent papers. Gene therapy was also discussed briefly, its present status and future.

  3. The prognostic value of clinical factors and cancer stem cell-related markers in gliomas

    Dahlrot, Rikke Hedegaard


    -renewal, proliferation, and differentiation during development of different (normal) tissues. The same characteristics were identified in cancer cells, and recently a major part of the glioma research has focused on the cancer stem cell (CSC) hypothesis, suggesting that only CSCs posses the ability of initiating new......UNLABELLED: Gliomas are the most frequent brain tumours among adults, and it is estimated that gliomas constitute half of the about 1500 new brain tumours diagnosed in Denmark every year. Existing treatment strategies include neurosurgery, radiation, and chemotherapy. Therapy selection is based...

  4. The WIND-HAARP Experiment: Initial Results of High Power Radiowave Interactions with Space Plasmas


    Results from the first science experiment with the new HF Active Auroral Research Program ( HAARP ) facility in Alaska are reported. The initial...experiments involved transmission of high frequency waves from HAARP to the NASA/WIND satellite. The objective was to investigate the effects of space

  5. Gamma knife treatment of rat glioma Influences of irradiation dose on apoptosis and necrosis

    Peng Wang; Mianshun Pan; Xinggen Fang


    BACKGROUND: Apoptosis and necrosis are cellular death mechanisms that are induced in glioma cells following gamma knife irradiation. Increased apoptosis is essential for maintaining and enhancing treatment efficacy.OBJECTIVE: To observe apoptotic and necrotic mechanisms of rat glioma models induced by gamma knife treatment and to analyze the influences of irradiation doses on apoptosis and necrosis. DESIGN: Controlled animal experiment. SETTING: Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital.MATERIALS: Eighteen female specific pathogen free Sprague Dawley rats, weighing 180-210 g and 5-6 weeks old, were purchased from the Experimental Animal Center, Medical College of Suzhou University. Rat C6 glioma cells were purchased from the cell bank of Chinese Academy of Sciences. Annexin V-FITC Reagent Kit (Bender Med System. Company, USA) and a flow cytometer (Becton Dickinson FACSCalibur) were provided.METHODS: The experiment was conducted at the Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital from December 2006 to May 2007. All rats were inoculated with C6 glioma cells, i.e., 4 μL of a C6 glioma cell suspension was injected 5 mm deep in the cortex. All rats were divided randomly into a model group, 9-Gy treatment group, and 12-Gy treatment group. There were six rats in each group.MAIN OUTCOME MEASURES: Apoptosis and necrosis of normal brain tissue and glioma were observed by Flow Cytometry one week after irradiation, and pathological changes to tumor tissue were identified by HE staining.RESULTS: Eighteen rats were initially selected for the study: two rats from the model and 12-Gy treatment groups died from accidental anesthesia. The remaining 16 rats were included in the final result analysis. Cellular apoptosis and necrosis: apoptosis and necrosis were significantly increased in the treatment groups after gamma knife irradiation, compared to the model group (P < 0

  6. Notch Promotes Radioresistance of Glioma Stem Cells

    Wang, Jialiang; Wakeman, Timothy P.; Latha, Justin D.; Hjelmeland, Anita B.; Wang, Xiao-Fan; White, Rebekah R.; Rich, Jeremy N.; Sullenger, Bruce A.


    Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we showed that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma st...

  7. Use of statins and risk of glioma

    Gaist, David; Andersen, L; Hallas, Jesper;


    Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.......Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting....

  8. Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma.

    Breunig, Joshua J; Levy, Rachelle; Antonuk, C Danielle; Molina, Jessica; Dutra-Clarke, Marina; Park, Hannah; Akhtar, Aslam Abbasi; Kim, Gi Bum; Hu, Xin; Bannykh, Serguei I; Verhaak, Roel G W; Danielpour, Moise


    As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.

  9. Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy

    Gregory K Friedman


    Full Text Available While glioblastoma multiforme (GBM is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed ‘glioma stem cells’ (GSCs, ‘glioma progenitor cells’, or ‘glioma-initiating cells', which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGGs must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses, genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oncolytic herpes simplex virus (HSV.

  10. Imaging of adult brainstem gliomas

    Purohit, Bela, E-mail:; Kamli, Ali A.; Kollias, Spyros S.


    Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

  11. Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma.

    Xiao-Yuan Liu

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM, the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro and in vivo glioma models, we observed that inhibition of eEF-2 kinase could enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was associated with blockade of autophagy and augmentation of apoptosis caused by TMZ. CONCLUSIONS/SIGNIFICANCE: These findings demonstrated that targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma.

  12. Isocitrate dehydrogenase mutations in gliomas.

    Waitkus, Matthew S; Diplas, Bill H; Yan, Hai


    Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.

  13. Rehabilitation of patients with glioma.

    Vargo, Mary; Henriksson, Roger; Salander, Pär


    Disabling sequelae occur in a majority of patients diagnosed with brain tumor, including glioma, such as cognitive deficits, weakness, and visual perceptual changes. Often, multiple impairments are present concurrently. Healthcare staff must be aware of the "biographic disruption" the patient with glioma has experienced. While prognostic considerations factor into rehabilitation goals and expectations, regardless of prognosis the treatment team must offer cohesive support, facilitating hope, function, and quality of life. Awareness of family and caregiver concerns plays an important role in the overall care. Inpatient rehabilitation, especially after surgical resection, has been shown to result in functional improvement and homegoing rates on a par with individuals with other neurologic conditions, such as stroke or traumatic brain injury. Community integration comprises a significant element of life satisfaction, as has been shown in childhood glioma survivors. Employment is often affected by the glioma diagnosis, but may be ameliorated, when appropriate, by addressing modifiable factors such as depression, fatigue, or sleep disturbance, or by workplace accommodations. Further research is needed into many facets of rehabilitation in the setting of glioma, including establishing better care models for consistently identifying and addressing functional limitations in this population, measuring outcomes of various levels of rehabilitation care, identifying optimal physical activity strategies, delineating the long-term effects of rehabilitation interventions, and exploring impact of rehabilitation interventions on caregiver burden. The effective elements of cognitive rehabilitation, including transition of cognitive strategies to everyday living, need to be better defined.

  14. Comparing overflow and wave-overtopping induced breach initiation mechanisms in an embankment breach experiment

    van Damme Myron


    Full Text Available As part of the SAFElevee project Delft University of Technology collabored with Flanders Hydraulics Research, and Infram B.V. in the preperation and execution of a full scale embankment breach experiment in November 2015. This breach experiment was performed on an 3.5m high embankment with a sand core and clay outer layer situated along the tidal river Scheldt in Belgium near Schellebelle. During the experiment a wave overtopping simulator and overflow simulator were used to initiate a breach. Both simulators were placed near the top of the waterside slope. The use of the simulators facilitated comparison between the effects of continueous overflow and the effects of intermittent wave overtopping. This paper presents the data collected during the experiment, describe the development of hypotheses on the failure processes using the latest insights, and comment on the failure initiation process of a grass covered flood embankment with a clay outer layer and a sandy core.

  15. Application of modified enzyme digestion method in rapid primary culture of human glioma cells

    Wei XIANG


    Full Text Available Objective  To explore the applied value of modified enzyme digestion method in primary culture of human glioma cells. Methods  A traditional enzyme digestion method was modified based on literatures and our work experience. The glioma cells from 32 glioma patients with different grades were primarily cultured by the modified enzyme digestion method. The morphological features of these cells were observed under an inverted phase contrast microscope. The primary cells were purified by differential adhesion during passage. The primary cells were identified by immunofluorescence technique, and the growth curves were drawn by cell proliferation assays (CCK-8 method for investigating the proliferation of the cells cultured in vitro. Results  The primary human glioma cells were successfully cultured and transferred by the new method, with a success rate of 87.5%. The cells cultured successfully in vitro showed good adherent growth, stable morphologies, thus can be passaged. Fluoroimmunoassay showed positive expression of glial fibrillary acidic protein, which confirms the cultured cells were glioma cells. Cell proliferation assays revealed active cell proliferation in vitro, the higher the tumor grade, the higher the proliferative capacity. Conclusion  The modified enzyme digestion method is simpler and more efficient for primary culture of human glioma cells, and the success rate is also higher, thus being able to provide a good guarantee for fundamental research of glioma. DOI: 10.11855/j.issn.0577-7402.2016.06.06

  16. Cellular factors promoting resistance to effective treatment of glioma with oncolytic myxoma virus.

    Zemp, Franz J; McKenzie, Brienne A; Lun, Xueqing; Reilly, Karlyne M; McFadden, Grant; Yong, V Wee; Forsyth, Peter A


    Oncolytic virus therapy is being evaluated in clinical trials for human glioma. While it is widely assumed that the immune response of the patient to the virus infection limits the utility of the therapy, investigations into the specific cell type(s) involved in this response have been performed using nonspecific pharmacologic inhibitors or allogeneic models with compromised immunity. To identify the immune cells that participate in clearing an oncolytic infection in glioma, we used flow cytometry and immunohistochemistry to immunophenotype an orthotopic glioma model in immunocompetent mice after Myxoma virus (MYXV) administration. These studies revealed a large resident microglia and macrophage population in untreated tumors, and robust monocyte, T-, and NK cell infiltration 3 days after MYXV infection. To determine the role on the clinical utility of MYXV therapy for glioma, we used a combination of knockout mouse strains and specific immunocyte ablation techniques. Collectively, our experiments identify an important role for tumor-resident myeloid cells and overlapping roles for recruited NK and T cells in the clearance and efficacy of oncolytic MYXV from gliomas. Using a cyclophosphamide regimen to achieve lymphoablation prior and during MYXV treatment, we prevented treatment-induced peripheral immunocyte recruitment and, surprisingly, largely ablated the tumor-resident macrophage population. Virotherapy of cyclophosphamide-treated animals resulted in sustained viral infection within the glioma as well as a substantial survival advantage. This study demonstrates that resistance to MYXV virotherapy in syngeneic glioma models involves a multifaceted cellular immune response that can be overcome with cyclophosphamide-mediated lymphoablation.

  17. Paediatric and adult malignant glioma

    Jones, Chris; Perryman, Lara; Hargrave, Darren


    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  18. Immunotherapy for malignant glioma

    Carter M Suryadevara


    Full Text Available Malignant gliomas (MG are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM, the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  19. Commissioning and initial experimental program of the BGO-OD experiment at ELSA

    Alef S.


    Full Text Available BGO-OD is a new meson photoproduction experiment at the ELSA facility of Bonn University. It aims at the investigation of non strange and strange baryon excitations, and is especially designed to be able to detect weekly bound meson-baryon type structures. The setup for the BGO-OD experiment is presented, the characteristics of the photon beam and the detector performances are shown and the initial experimental program is discussed.

  20. Frequent Nek1 overexpression in human gliomas

    Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)


    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  1. Neuronavigator-guided glioma surgery

    杜固宏; 周良辅; 毛颖


    Objective To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. Methods A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift.Results Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm±0.89 mm and 2.43 mm±0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm±2.39 mm, 7.58 mm±3.75 mm, and 6.55 mm±3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. Conclusions Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

  2. Prognostic Marker before Treatment of Patients with Malignant Glioma

    Norbert Galldiks


    Full Text Available The purpose of this positron emission tomography (PET study was to compare the prognostic value of pretreatment volume of [11C] methionine (MET uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients′ pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA. Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients′ outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

  3. Senescence from glioma stem cell differentiation promotes tumor growth

    Ouchi, Rie [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Okabe, Sachiko; Migita, Toshiro [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakano, Ichiro [Department of Neurosurgery, Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35233 (United States); Seimiya, Hiroyuki, E-mail: [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan)


    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  4. Pediatric gliomas as neurodevelopmental disorders.

    Baker, Suzanne J; Ellison, David W; Gutmann, David H


    Brain tumors represent the most common solid tumor of childhood, with gliomas comprising the largest fraction of these cancers. Several features distinguish them from their adult counterparts, including their natural history, causative genetic mutations, and brain locations. These unique properties suggest that the cellular and molecular etiologies that underlie their development and maintenance might be different from those that govern adult gliomagenesis and growth. In this review, we discuss the genetic basis for pediatric low-grade and high-grade glioma in the context of developmental neurobiology, and highlight the differences between histologically-similar tumors arising in children and adults.

  5. Expanding indications for the extended endoscopic endonasal approach to hypothalamic gliomas: preliminary report.

    Zoli, Matteo; Mazzatenta, Diego; Valluzzi, Adelaide; Marucci, Gianluca; Acciarri, Nicola; Pasquini, Ernesto; Frank, Giorgio


    Object In the last decade the indications for the endoscopic endonasal approach have been progressively expanded to include lesions that have not been traditionally considered amenable to resection through the transsphenoidal route. In this study, the authors analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking

  6. Initiating Transdisciplinarity in Academic Case Study Teaching: Experiences from a Regional Development Project in Salzburg, Austria

    Muhar, Andreas; Vilsmaier, Ulli; Glanzer, Michaela; Freyer, Bernhard


    Purpose: The purpose of this paper is to describe experiences with the initiation of transdisciplinarity in academic case study teaching with special reference to regional planning, based on the case study "Leben 2014 (Life 2014)--perspectives for regional development in the national park region Ober-pinz-gau, Salzburg".…

  7. "Elite" Career-Changers and Their Experience of Initial Teacher Education

    Wilkins, Chris


    This study explores the motivation of "high-status" professionals to change career and enter teaching, and their experience of undertaking initial teacher education (ITE) programmes in England. The study builds on previous research which found that career-changers are disproportionately more likely to fail to complete their ITE studies,…

  8. Initial Experience with the Extracorporeal HIFU Knife with 49 Patients: Japanese Experience

    Ganaha, F.; Okuno, T.; Lee, C. O.; Shimizu, T.; Osako, K.; Oka, S.; Lee, K. H.; Chen, W. Z.; Zhu, H.; Park, S. H.; Qi, Z.; Shi, D.; Song, H. S.


    Forty nine patients with 63 tumours were treated with the Chongqing Haifu knife, as an adjunct to intra-arterial chemoinfusion. Treatment targets included breast (20 lesions), liver (16), bone (8), lymph-node (6), soft tissue (4), lung and pleura (4), pancreas (2), kidney (2) and adrenal gland (1). Follow-up contrast MRI was performed at 3 weeks to assess the effects of HIFU ablation. All cases completed the planned treatment. Of 25 lesions treated with the intention of complete tumour ablation, complete necrosis was obtained in 19 lesions (76%) including 4 secondary success cases. Among 32 lesions having partial and palliative treatment, tumour size was decreased in 6 lesions (21%), and good pain control was obtained in 6 out of 7 patients (86%). Skin injury was the most common complication after HIFU (16%), and was mostly a superficial dermal burn that did not necessitate any treatment. However, there was one patient with deep skin injury at an operation scar which resulted in skin perforation. Other adverse events included soft tissue swelling, prolonged fever, anorexia, persistent pain, shortness of the breath, sacroiliac joint fracture and prolonged diarrhoea. In our limited experience, superficial lesions (e.g. breast cancer, bone, soft tissue, lymph-node and pleural metastasis) appear to be good candidates for HIFU treatment. There appears to be a role for the HIFU knife in pain control for patients with bone metastasis and pancreatic cancer.

  9. Critical Neural Networks in Awake Surgery for Gliomas

    KINOSHITA, Masashi; MIYASHITA, Katsuyoshi; TSUTSUI, Taishi; FURUTA, Takuya; NAKADA, Mitsutoshi


    From the embarrassing character commonly infiltrating eloquent brain regions, the surgical resection of glioma remains challenging. Owing to the recent development of in vivo visualization techniques for the human brain, white matter regions can be delineated using diffusion tensor imaging (DTI) as a routine clinical practice in neurosurgery. In confirmation of the results of DTI tractography, a direct electrical stimulation (DES) substantially influences the investigation of cortico-subcortical networks, which can be identified via specific symptoms elicited in the concerned white matter tracts (eg., the arcuate fascicle, superior longitudinal fascicles, inferior fronto-occipital fascicle, inferior longitudinal fascicle, frontal aslant tract, sensori-motor tracts, optic radiation, and so forth). During awake surgery for glioma using DES, it is important to identify the anatomo-functional structure of white matter tracts to identify the surgical boundaries of brain regions not only to achieve maximal resection of the glioma but also to maximally preserve quality of life. However, the risk exists that neurosurgeons may be misled by the inability of DTI to visualize the actual anatomy of the white matter fibers, resulting in inappropriate decisions regarding surgical boundaries. This review article provides information of the critical neuronal network that is necessary to identify and understand in awake surgery for glioma, with special references to white matter tracts and the author’s experiences. PMID:27250817

  10. Exogenous p16 gene therapy combined with X-ray irradiation suppresses the growth of human glioma cells

    Hongbing Ma; Zhengli Di; Minghua Bai; Hongtao Ren; Zongfang Li


    In this study, we infected human glioma U251 cells with a replication-defective recombinant adeno-virus carrying the p16 gene. This adenovirus constructed was able to transfect exogenous p16 into the human glioma cells efficiently, and direct a high level of p16 protein expression. Tumor-inhibition experiments demonstrated that treatment with the adenovirus-p16 significantly inhibited the growth of glioma cells in vitro as well as the in vivo development of tumors in nude mice bearing a brain glioma. The combination of adenovirus-p16 gene treatment and X-ray irradiation resulted in a greater inhibition of tumor growth. Adenovirus-mediated p16 gene therapy conferred a significant antitumor effect against human glioma cells both in vitro and in vivo, and that there was a synergistic effect when X-ray irradiation was also used.

  11. Influence of the initial soil water content on Beerkan water infiltration experiments

    Lassabatere, L.; Loizeau, S.; Angulo-Jaramillo, R.; Winiarski, T.; Rossier, Y.; Delolme, C.; Gaudet, J. P.


    Understanding and modeling of water flow in the vadose zone are important with regards water management and infiltration devices design. Water infiltration process clearly depends on initial soil water content, in particular for sandy soils with high organic matter content. This study investigates the influence of initial water content on water infiltration in a hydrophobic sandy soil and on the related derivation of hydraulic parameters using the BEST algorithm (Lassabatere et al., 2006). The studied sandy soil has a high total organic content decreasing from 3.5% (w/w) at the surface to 0.5% (w/w) below 1cm depth. The highest TOC at surface was due to the presence of a dense biofilm and resulted in a high surface hydrophobicity under dry conditions (low initial water contents). The water infiltration experiments consisted in infiltrating known volumes of water through a simple ring at null pressure head (Beerkan method). The infiltrations were performed during three successive days after a dry period with a storm event between the first and the second day (5 mm) and another between the second and the third day (35 mm). These events resulted in an increase in initial water contents, from less than 5% for the first day to around 10% for the last day. Experiments were performed for appropriate conditions for Beerkan experiments: initial water contents below 1/4 of the saturated water content and uniform water profile resulting from water redistribution after each rainfall event. The analysis of the infiltration data clearly highlights the strong effect of hydrophobicity. For the driest initial conditions (first day), infiltration rates increased with time, whereas they decreased with time for wetter conditions. Such a decrease agreed with the principles of water infiltration without hydrophobicity. In addition, total cumulative infiltrations were far higher for the wettest conditions. Regarding hydraulic characterization, only the data obtained during the last

  12. High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes.

    Dijksterhuis, Jacomijn P; Arthofer, Elisa; Marinescu, Voichita D; Nelander, Sven; Uhlén, Mathias; Pontén, Frederik; Mulder, Jan; Schulte, Gunnar


    Malignant gliomas are among the most severe types of cancer, and the most common primary brain tumors. Treatment options are limited and the prognosis is poor. WNT-5A, a member of the WNT family of lipoglycoproteins, plays a role in oncogenesis and tumor progression in various cancers, whereas the role of WNT-5A in glioma remains obscure. Based on the role of WNT-5A as an oncogene, its potential to regulate microglia cells and the glioma-promoting capacities of microglia cells, we hypothesize that WNT-5A has a role in regulation of immune functions in glioma. We investigated WNT-5A expression by in silico analysis of the cancer genome atlas (TCGA) transcript profiling of human glioblastoma samples and immunohistochemistry experiments of human glioma tissue microarrays (TMA). Our results reveal higher WNT-5A protein levels and mRNA expression in a subgroup of gliomas (WNT-5A(high)) compared to non-malignant control brain tissue. Furthermore, we show a significant correlation between WNT-5A in the tumor and presence of major histocompatibility complex Class II-positive microglia/monocytes. Our data pinpoint a positive correlation between WNT-5A and a proinflammatory signature in glioma. We identify increased presence of microglia/monocytes as an important aspect in the inflammatory transformation suggesting a novel role for WNT-5A in human glioma.

  13. Genetic and Epigenetic Modifications of Sox2 Contribute to the Invasive Phenotype of Malignant Gliomas

    Alonso, Marta M.; Diez-Valle, Ricardo; Manterola, Lorea; Rubio, Angel; Liu, Dan; Cortes-Santiago, Nahir; Urquiza, Leire; Jauregi, Patricia; de Munain, Adolfo Lopez; Sampron, Nicolás; Aramburu, Ander; Tejada-Solís, Sonia; Vicente, Carmen; Odero, María D.; Bandrés, Eva; García-Foncillas, Jesús; Idoate, Miguel A.; Lang, Frederick F.; Fueyo, Juan; Gomez-Manzano, Candelaria


    We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM), the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414), Sox2 gene amplification (8.5%; N = 492), and Sox 2 promoter hypomethylation (100%; N = 258), suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs) and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM. PMID:22069467

  14. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas.

    Marta M Alonso

    Full Text Available We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM, the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414, Sox2 gene amplification (8.5%; N = 492, and Sox 2 promoter hypomethylation (100%; N = 258, suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM.

  15. Experiments and simulations on the incompressible, Rayleigh-Taylor instability with small wavelength initial perturbations

    Roberts, Michael Scott

    The Rayleigh-Taylor instability is a buoyancy driven instability that takes place in a stratified fluid system with a constant acceleration directed from the heavy fluid into the light fluid. In this study, both experimental data and numerical simulations are presented. Experiments are performed primarily using a lithium-tungstate aqueous solution as the heavy liquid, but sometimes a calcium nitrate aqueous solution is used for comparison purposes. Experimental data is obtained for both miscible and immiscible fluid combinations. For the miscible experiments the light liquid is either ethanol or isopropanol, and for the immiscible experiments either silicone oil or trans-anethole is used. The resulting Atwood number is either 0.5 when the lithium-tungstate solution is used or 0.2 when the calcium nitrate solution is used. These fluid combinations are either forced or left unforced. The forced experiments have an initial perturbation imposed by vertically oscillating the liquid containing tank to produce Faraday waves at the interface. The unforced experiments rely on random interfacial fluctuations, due to background noise, to seed the instability. The liquid combination is partially enclosed in a test section that is accelerated downward along a vertical rail system causing the Rayleigh-Taylor instability. Accelerations of approximately 1g (with a weight and pulley system) or 10g (with a linear induction motor system) are experienced by the liquids. The tank is backlit and digitally recorded with high speed video cameras. These experiments are then simulated with the incompressible, Navier-Stokes code Miranda. The main focus of this study is the growth parameter (α) of the mixing region produced by the instability after it has become apparently self-similar and turbulent. The measured growth parameters are compared to determine the effects of miscibility and initial perturbations (of the small wavelength, finite bandwidth type used here). It is found that while

  16. Migration experience and premarital sexual initiation in urban Kenya: an event history analysis.

    Luke, Nancy; Xu, Hongwei; Mberu, Blessing U; Goldberg, Rachel E


    Migration during the formative adolescent years can affect important life-course transitions, including the initiation of sexual activity. In this study, we use life history calendar data to investigate the relationship between changes in residence and timing of premarital sexual debut among young people in urban Kenya. By age 18, 64 percent of respondents had initiated premarital sex, and 45 percent had moved at least once between the ages of 12 and 18. Results of the event history analysis show that girls and boys who move during early adolescence experience the earliest onset of sexual activity. For adolescent girls, however, other dimensions of migration provide protective effects, with greater numbers of residential changes and residential changes in the last one to three months associated with later sexual initiation. To support young people's ability to navigate the social, economic, and sexual environments that accompany residential change, researchers and policymakers should consider how various dimensions of migration affect sexual activity.

  17. MicroRNA in Human Glioma

    Li, Mengfeng, E-mail: [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Li, Jun [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Lei; Li, Wei [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yang, Yi [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yuan, Jie [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Key Laboratory of Functional Molecules from Oceanic Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou 510080 (China)


    Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy.

  18. Causes and outcomes of revisional bariatric surgery: initial experience at a single center


    Purpose Bariatric surgery has become more prevalent owing to the worldwide obesity epidemic. With the growing number of bariatric procedures performed annually, the requirement for revisional and secondary operations is increasing accordingly. This study aimed to evaluate the initial experience of revisional bariatric surgery at a single specialized center. Methods A retrospective review of the prospectively established database identified all patients who underwent revisional bariatric surge...

  19. Initial experience with a first-to-market member accountability-based insurance product.

    Woll, Douglas R; Nelson, David R


    We describe the initial experience with a first-to-market health insurance product design based on principles of both member and purchaser accountability. Two benefit levels were offered, enhanced and standard. Qualification for the enhanced benefit level was obtained through members' commitment to follow their physicians' recommended treatment plan. Employers were offered a discount of 10% in exchange for offering this new product and promoting a healthy work environment. Membership in the product grew beyond expectations, and several health improvements were noted.

  20. Down-regulation of neogenin accelerated glioma progression through promoter Methylation and its overexpression in SHG-44 Induced Apoptosis.

    Xinmin Wu

    Full Text Available BACKGROUND: Dependence receptors have been proved to act as tumor suppressors in tumorigenesis. Neogenin, a DCC homologue, well known for its fundamental role in axon guidance and cellular differentiation, is also a dependence receptor functioning to control apoptosis. However, loss of neogenin has been reported in several kinds of cancers, but its role in glioma remains to be further investigated. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analysis showed that neogenin level was lower in glioma tissues than in their matching surrounding non-neoplastic tissues (n = 13, p<0.01. By immunohistochemical analysis of 69 primary and 16 paired initial and recurrent glioma sections, we found that the loss of neogenin did not only correlate negatively with glioma malignancy (n = 69, p<0.01, but also glioma recurrence (n = 16, p<0.05. Kaplan-Meier plot and Cox proportional hazards modelling showed that over-expressive neogenin could prolong the tumor latency (n = 69, p<0.001, 1187.6 ± 162.6 days versus 687.4 ± 254.2 days and restrain high-grade glioma development (n = 69, p<0.01, HR: 0.264, 95% CI: 0.102 to 0.687. By Methylation specific polymerase chain reaction (MSP, we reported that neogenin promoter was methylated in 31.0% (9/29 gliomas, but absent in 3 kinds of glioma cell lines. Interestingly, the prevalence of methylation in high-grade gliomas was higher than low-grade gliomas and non-neoplastic brain tissues (n = 33, p<0.05 and overall methylation rate increased as glioma malignancy advanced. Furthermore, when cells were over-expressed by neogenin, the apoptotic rate in SHG-44 was increased to 39.7% compared with 8.1% in the blank control (p<0.01 and 9.3% in the negative control (p<0.01. CONCLUSIONS/SIGNIFICANCE: These observations recapitulated the proposed role of neogenin as a tumor suppressor in gliomas and we suggest its down-regulation owing to promoter methylation is a selective advantage for glioma genesis, progression and recurrence

  1. Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

    de Almeida Sassi, Felipe; Lunardi Brunetto, Algemir; Schwartsmann, Gilberto; Roesler, Rafael; Abujamra, Ana Lucia


    Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment. PMID:22973309

  2. Evaluation of TAZ expression and its effect on tumor invasion and metastasis in human glioma

    Pei-Dong Li; Xin-Jun Wang; Qiao Shan; Yue-Hui Wu; Zhen Wang


    Objective:To evaluate the expression ofTAZ and its role in tumor invasion and metastasis in human glioma.Methods:The expression ofTAZ protein was measured in48 samples of surgically resected human glioma and13 samples of normal brain tissues using immunohistochemistry. TAZ was knocked down by a retrovirus-mediatedTAZ shRNA in a glioma cell line,SNB19. Transwell cell migration and invasion assays were used to determine migration and invasion ofSNB19 cells.Results:The positive expression rate ofTAZ protein in glioma tissues was significantly higher than that in normal brain tissues(79.2%vs.15.4%,P<0.001).Furthermore, clinical analysis suggested that the positive expression rate ofTAZ protein in poorly differentiated tumor tissues was significantly higher as compared with that in well differentiated tissues(96.0%vs.60.9%,P<0.01).TAZ was significantly knocked down byTAZ shRNA(P<0.001), andTAZ knockdown significantly reduced cell migration and invasion(P<0.01, respectively) inSNB19 cells.Conclusions:TAZ protein overexpression is observed in human glioma and its elevated expression is significantly correlated with poor differentiation.TAZ knockdown prominently reduces cell migration and invasion inSNB19 cells, suggesting thatTAZ may play a key role in the initiation and progression of human glioma.

  3. Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma.

    Kessler, Tobias; Sahm, Felix; Blaes, Jonas; Osswald, Matthias; Rübmann, Petra; Milford, David; Urban, Severino; Jestaedt, Leonie; Heiland, Sabine; Bendszus, Martin; Hertenstein, Anne; Pfenning, Philipp-Niclas; Ruiz de Almodóvar, Carmen; Wick, Antje; Winkler, Frank; von Deimling, Andreas; Platten, Michael; Wick, Wolfgang; Weiler, Markus


    Loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a prerequisite for tumor cell-specific expression of vascular endothelial growth factor receptor (VEGFR)-2 in glioblastoma defining a subgroup prone to develop evasive resistance towards antiangiogenic treatments. Immunohistochemical analysis of human tumor tissues showed VEGFR-2 expression in glioma cells in 19% of specimens examined, mainly in the infiltration zone. Glioma cell VEGFR-2 positivity was restricted to PTEN-deficient tumor specimens. PTEN overexpression reduced VEGFR-2 expression in vitro, as well as knock-down of raptor or rictor. Genetic interference with VEGFR-2 revealed proproliferative, antiinvasive and chemoprotective functions for VEGFR-2 in glioma cells. VEGFR-2-dependent cellular effects were concomitant with activation of 'kappa-light-chain-enhancer' of activated B-cells, protein kinase B, and N-myc downstream regulated gene 1. Two-photon in vivo microscopy revealed that expression of VEGFR-2 in glioma cells hampers antiangiogenesis. Bevacizumab induces a proinvasive response in VEGFR-2-positive glioma cells. Patients with PTEN-negative glioblastomas had a shorter survival after initiation of bevacizumab therapy compared with PTEN-positive glioblastomas. Conclusively, expression of VEGFR-2 in glioma cells indicates an aggressive glioblastoma subgroup developing early resistance to temozolomide or bevacizumab. Loss of PTEN may serve as a biomarker identifying those tumors upfront by routine neuropathological methods.

  4. Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells.

    Bi, Yunke; Shen, Chen; Li, Chenguang; Liu, Yaohua; Gao, Dandan; Shi, Chen; Peng, Fei; Liu, Zhendong; Zhao, Boxian; Zheng, Zhixing; Wang, Xiaoxiong; Hou, Xu; Liu, Huailei; Wu, Jianing; Zou, Huichao; Wang, Kaikai; Zhong, Chen; Zhang, Jiakang; Shi, Changbin; Zhao, Shiguang


    Glioma is the most common primary brain tumor in the central nervous system (CNS) with high morbidity and mortality in adults. Although standardized comprehensive therapy has been adapted, the prognosis of glioma patients is still frustrating and thus novel therapeutic strategies are urgently in need. Quercetin (Quer), an important flavonoid compound found in many herbs, is shown to be effective in some tumor models including glioma. Recently, it is reported that adequate regulation of autophagy can strengthen cytotoxic effect of anticancer drugs. However, it is not yet fully clear how we should modulate autophagy to achieve a satisfactory therapeutic effect. 3-Methyladenine (3-MA) and Beclin1 short hairpin RNA (shRNA) were used to inhibit the early stage of autophage while chloroquine (CQ) to inhibit the late stage. MTT assay was implemented to determine cell viability. Transmission electron microscopy, western blot, and immunohistochemistry were adopted to evaluate autophagy. Western blot, flow cytometry, and immunohistochemistry were used to detect apoptosis. C6 glioma xenograft models were established to assess the therapeutic effect (the body weight change, the median survival time, and tumor volume) in vivo. Quercetin can inhibit cell viability and induce autophagy of U87 and U251 glioma cells in a dose-dependent manner. Inhibition of early-stage autophagy by 3-MA or shRNA against Beclin1 attenuated the quercetin-induced cytotoxicity. In contrast, suppression of autophagy at a late stage by CQ enhanced the anti-glioma efficiency of quercetin. Therapeutic effect of quercetin for malignant glioma can be strengthened by inhibition of autophagy at a late stage, not initial stage, which may provide a novel opportunity for glioma therapy.

  5. The role of autophagy in sensitizing malignant glioma cells to radiation therapy

    Wenzhuo Zhuang; Zhenghong Qin; Zhongqin Liang


    Malignant gliomas representthe majority of primary brain tumors.The current standard treatments for malignant gliomas include surgical resection,radiation therapy,and chemotherapy.Radiotherapy,a standard adjuvant therapy,confers some survival advantages,but resistance of the glioma cells to the efficacy of radiation limits the success of the treatment.The mechanisms underlying glioma cell radioresistance have remained elusive.Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm.Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy.Also,autophagy is a novel response of glioma cells to ionizing radiation.Autophagic cell death is considered programmed cell death type Ⅱ,whereas apoptosis is programmed cell death type Ⅰ.These two types of cell death are predominantly distinctive,but many studies demonstrate a cross-talk between them.Whether autophagy in cancer cells causes death or protects cells is controversial.The regulatory pathways of autophagy share several molecules.P13K/Akt/Mtor,DNA-PK,tumor suppressor genes, mitochondrial damage,and lysosome may play important roles in radiation-induced autophagy in glioma cells.Recently,a highly tumorigenic glioma tumor subpopulation,termed cancer stem cell or tumor-initiating cell,has been shown to promote therapeutic resistance.This review summarizes the main mediators associated with radiation-induced autophagy in malignant glioma cells and discusses the implications of the cancer stem cell hypothesis for the development of future therapies for brain tumors.

  6. Thermophysical Property Estimation by Transient Experiments: The Effect of a Biased Initial Temperature Distribution

    Federico Scarpa


    Full Text Available The identification of thermophysical properties of materials in dynamic experiments can be conveniently performed by the inverse solution of the associated heat conduction problem (IHCP. The inverse technique demands the knowledge of the initial temperature distribution within the material. As only a limited number of temperature sensors (or no sensor at all are arranged inside the test specimen, the knowledge of the initial temperature distribution is affected by some uncertainty. This uncertainty, together with other possible sources of bias in the experimental procedure, will propagate in the estimation process and the accuracy of the reconstructed thermophysical property values could deteriorate. In this work the effect on the estimated thermophysical properties due to errors in the initial temperature distribution is investigated along with a practical method to quantify this effect. Furthermore, a technique for compensating this kind of bias is proposed. The method consists in including the initial temperature distribution among the unknown functions to be estimated. In this way the effect of the initial bias is removed and the accuracy of the identified thermophysical property values is highly improved.

  7. The Glioma International Case-Control Study

    Amirian, E. Susan; Armstrong, Georgina N; Zhou, Renke


    Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly...... describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen...

  8. Experience shapes our odor perception but depends on the initial perceptual processing of the stimulus.

    Sinding, Charlotte; Coureaud, Gérard; Bervialle, Boris; Martin, Christophe; Schaal, Benoist; Thomas-Danguin, Thierry


    The questions of whether configural and elemental perceptions are competitive or exclusive perceptual processes and whether they rely on independent or dependent mechanisms are poorly understood. To examine these questions, we modified perceptual experience through preexposure to mixed or single odors and measured the resulting variation in the levels of configural and elemental perception of target odor mixtures. We used target mixtures that were spontaneously processed in a configural or an elemental manner. The AB binary mixture spontaneously involved the configural perception of a pineapple odor, whereas component A smelled like strawberry and component B smelled like caramel. The CD mixture produced the elemental perceptions of banana (C) and smoky (D) odors. Perceptual experience was manipulated through repeated exposure to either a mixture (AB or CD) or the components (A and B or C and D). The odor typicality rating data recorded after exposure revealed different influences of experience on odor mixtures and single-component perception, depending both on the type of exposure (components or mixture) and the mixture's initial perceptual property (configural or elemental). Although preexposure to A and B decreased the pineapple typicality of the configural AB mixture, preexposure to AB did not modify its odor quality. In contrast, preexposure to the CD elemental mixture induced a quality transfer between the components. These results emphasize the relative plasticity of odor mixture perception, which is prone to experience-induced modulations but depends on the stimulus's initial perceptual properties, suggesting that configural and elemental forms of odor mixture perception rely on rather independent processes.

  9. Magnetohydrodynamic simulation of solid-deuterium-initiated Z-pinch experiments

    Sheehey, Peter Trogdon [Univ. of California, Los Angeles, CA (United States)


    Solid-deuterium-initiated Z-pinch experiments are numerically simulated using a two-dimensional resistive magnetohydrodynamic model, which includes many important experimental details, such as ``cold-start`` initial conditions, thermal conduction, radiative energy loss, actual discharge current vs. time, and grids of sufficient size and resolution to allow realistic development of the plasma. The alternating-direction-implicit numerical technique used meets the substantial demands presented by such a computational task. Simulations of fiber-initiated experiments show that when the fiber becomes fully ionized rapidly developing m=0 instabilities, which originated in the coronal plasma generated from the ablating fiber, drive intense non-uniform heating and rapid expansion of the plasma column. The possibility that inclusion of additional physical effects would improve stability is explored. Finite-Larmor-radius-ordered Hall and diamagnetic pressure terms in the magnetic field evolution equation, corresponding energy equation terms, and separate ion and electron energy equations are included; these do not change the basic results. Model diagnostics, such as shadowgrams and interferograms, generated from simulation results, are in good agreement with experiment. Two alternative experimental approaches are explored: high-current magnetic implosion of hollow cylindrical deuterium shells, and ``plasma-on-wire`` (POW) implosion of low-density plasma onto a central deuterium fiber. By minimizing instability problems, these techniques may allow attainment of higher temperatures and densities than possible with bare fiber-initiated Z-pinches. Conditions for significant D-D or D-T fusion neutron production may be realizable with these implosion-based approaches.

  10. Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma.

    Eagan, R T; Childs, D S; Layton, D D; Laws, E R; Bisel, H F; Holbrook, M A; Fleming, T R


    Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.

  11. Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects.

    Liu, Yong-Chang; Wang, Yan-zhou


    The activation of proline-rich phosphoprotein Yes-associated protein 1 (YAP1) possesses a possible link between stem/progenitor cells, organ size, and cancer. YAP1 has been indicated as an oncoprotein, and overexpression of YAP1 is reported in many human brain tumors, including infiltrating gliomas. During normal brain development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in neural progenitor cells to promote guidepost cell differentiation, but loss of NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts guidepost formation. Overexpression of endogenous CD44 (cancer stem cell marker) promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and leads to cancer cell resistance in glioblastoma. The hippo pathway is also related to the YAP1 action. However, the mechanism of YAP1 action in glioma is still far from clear understanding. Advances in clinical management based on an improved understanding of the function of YAP1 may help to serve as a molecular target in glioma therapeutics. Knockdown of YAP1 by shRNA technology has been shown to reduce glioma in vitro; however, clinical implications are still under investigation. YAP1 can be used as a diagnostic marker for gliomas to monitor the disease status and may help to evaluate its treatment effects. More functional experiments are needed to support the direct roles of YAP1 on gliomas at molecular and cellular levels.

  12. Tumor Metabolism of Malignant Gliomas

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)


    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  13. Tumor Metabolism of Malignant Gliomas

    Deliang Guo


    Full Text Available Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  14. Initial Scaling Studies and Conceptual Thermal Fluids Experiments for the Prismatic NGNP Point Design

    D. M. McEligot; G. E. McCreery


    The objective of this report is to document the initial high temperature gas reactor scaling studies and conceptual experiment design for gas flow and heat transfer. The general approach of the project is to develop new benchmark experiments for assessment in parallel with CFD and coupled CFD/ATHENA/RELAP5-3D calculations for the same geometry. Two aspects of the complex flow in an NGNP are being addressed: (1) flow and thermal mixing in the lower plenum ("hot streaking" issue) and (2) turbulence and resulting temperature distributions in reactor cooling channels ("hot channel" issue). Current prismatic NGNP concepts are being examined to identify their proposed flow conditions and geometries over the range from normal operation to decay heat removal in a pressurized cooldown. Approximate analyses are being applied to determine key non-dimensional parameters and their magnitudes over this operating range. For normal operation, the flow in the coolant channels can be considered to be dominant forced convection with slight transverse property variation. The flow in the lower plenum can locally be considered to be a situation of multiple buoyant jets into a confined density-stratified crossflow -- with obstructions. Experiments are needed for the combined features of the lower plenum flows. Missing from the typical jet experiments are interactions with nearby circular posts and with vertical posts in the vicinity of vertical walls - with near stagnant surroundings at one extreme and significant crossflow at the other. Two heat transfer experiments are being considered. One addresses the "hot channel" problem, if necessary. The second experiment will treat heated jets entering a model plenum. Unheated MIR (Matched-Index-of-Refraction) experiments are first steps when the geometry is complicated. One does not want to use a computational technique which will not even handle constant properties properly. The MIR experiment will simulate flow features of the paths of jets

  15. The Pathobiology of Glioma Tumors

    Gladson, Candece L.; Prayson, Richard A.; LIU Wei


    The ongoing characterization of the genetic and epigenetic alterations in the gliomas has already improved the classification of these heterogeneous tumors and enabled the development of rodent models for analysis of the molecular pathways underlying their proliferative and invasive behavior. Effective application of the targeted therapies that are now in development will depend on pathologists’ ability to provide accurate information regarding the genetic alterations and the expression of ke...

  16. Effects of Initial Conditions on Compressible Mixing in Supernova-Relevant Laboratory Experiments

    Miles, A R; Edwards, M; Greenough, J


    In core-collapse supernovae, strong blast waves drive interfaces susceptible to Rayleigh-Taylor (RT), Richtmyer-Meshkov (RM), and Kelvin-Helmholtz (KH) instabilities. In addition, perturbation growth can result from material expansion in large-scale velocity gradients behind the shock front. Laser-driven experiments are designed to produce a strongly shocked interface whose evolution is a scaled version of the unstable hydrogen-helium interface in core-collapse supernovae such as SN 1987A. The ultimate goal of this research is to develop an understanding of the effect of hydrodynamic instabilities and the resulting transition to turbulence on supernovae observables that remain as yet unexplained. In this paper, we summarize recent results from our computational study of unstable systems driven by high Mach number shock and blast waves. For planar multimode systems, compressibility effects preclude the emergence of a regime of self-similar instability growth independent of the initial conditions (IC's) by allowing for memory of the initial conditions to be retained in the mix-width at all times. With higher-dimensional blast waves, divergence restores the properties necessary for establishment of the self-similar state, but achieving it requires very high initial characteristic mode number and high Mach number for the incident blast wave. Initial conditions predicted by some recent stellar calculations are incompatible with self-similarity.

  17. Initial utility experience with cluster of three Mod-2 wind turbine systems

    Seely, D. B.; Warchol, E. J.; Butler, N. G.; Ciranny, S.


    This paper describes the initial utility experiences of operating three MOD-2s during the Engineering Acceptance Testing. Electrical quantities of bus voltage, phase currents and power are initially being recorded to evaluate impacts to customers on the 69-kV subtransmission line during synchronization and operation of one or more WTSs. To date, effects on the system have been essentially undetectable. Measurements of television signal strengths were taken at an existing television remote pickup and relay station at the WTS site. Potential TV signal interference problems from the WTSs have been avoided by replacing the remote pickups with microwave repeater links for the four TV channels received from Portland, Oregon. Preliminary measurements of audible and sub-audible noise levels indicate that the upwind rotor, tubular tower design of the MOD-2 does not have the pulsing high intensity infrasound problems experienced by the MOD-1 machine at Boone, North Carolina.

  18. Experience of initiating collaboration of traditional healers in managing HIV and AIDS in Tanzania

    Moshi Mainen J


    Full Text Available Abstract Collaboration between traditional healers and biomedical practitioners is now being accepted by many African countries south of the Sahara because of the increasing problem of HIV/AIDS. The key problem, however, is how to initiate collaboration between two health systems which differ in theory of disease causation and management. This paper presents findings on experience learned by initiation of collaboration between traditional healers and the Institute of Traditional Medicine in Arusha and Dar-es-Salaam Municipalities, Tanzania where 132 and 60 traditional healers respectively were interviewed. Of these 110 traditional healers claimed to be treating HIV/AIDS. The objective of the study was to initiate sustainable collaboration with traditional healers in managing HIV/AIDS. Consultative meetings with leaders of traditional healers' associations and government officials were held, followed by surveys at respective traditional healers' "vilinge" (traditional clinics. The findings were analysed using both qualitative and quantitative methods. The findings showed that influential people and leaders of traditional healers' association appeared to be gatekeepers to access potential good healers in the two study areas. After consultative meetings these leaders showed to be willing to collaborate; and opened doors to other traditional healers, who too were willing to collaborate with the Institute of Traditional Medicine in managing HIV/AIDS patients. Seventy five percent of traditional healers who claimed to be treating HIV/AIDS knew some HIV/AIDS symptoms; and some traditional healers attempted to manage these symptoms. Even though, they were willing to collaborate with the Institute of Traditional Medicine there were nevertheless some reservations based on questions surrounding sharing from collaboration. The reality of past experiences of mistreatment of traditional healers in the colonial period informed these reservations. General

  19. Retinoids in the treatment of glioma: a new perspective

    Mawson AR


    Full Text Available Anthony R MawsonDepartment of Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University, Jackson, MS, USAAbstract: Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α(RARα and reduced expression of retinoic acid receptor-β (RARβ. This suggests a potential new treatment strategy for gliomas, possibly even at a

  20. RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth

    Anne C. Solga


    Full Text Available Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia represent rich sources of these stromal factors. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1 low-grade brain tumor (optic glioma, we have previously demonstrated that microglia are essential for glioma formation and maintenance. To identify potential tumor-associated microglial factors that support glioma growth (gliomagens, we initiated a comprehensive large-scale discovery effort using optimized RNA-sequencing methods focused specifically on glioma-associated microglia. Candidate microglial gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative real-time polymerase chain reaction as well as by RNA fluorescence in situ hybridization following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, chemokine (C-C motif ligand 5 (Ccl5 was identified as a chemokine highly expressed in genetically engineered Nf1 mouse optic gliomas relative to nonneoplastic optic nerves. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, treatment with Ccl5 neutralizing antibodies reduced Nf1 mouse optic glioma growth and improved retinal dysfunction in vivo. Collectively, these findings establish Ccl5 as an important microglial growth factor for low-grade glioma maintenance relevant to the development of future stroma-targeted brain tumor therapies.

  1. Maximizing the Workshop Experience: An Example from the PTRA Rural Initiatives Program

    Burns, Teresa


    Since the summer of 2001, the Rural Initiative of the Physics Teaching Resource Agents have led summer workshops for high school and middle school physics teachers at several universities nationwide. From the site at Coastal Carolina University where teachers learned about radioactivity and nuclear physics, assistant professor Teresa Burns describes how high school teacher Lucas Mullen was able to build a curriculum tied to South Carolina State Science Standards around the content he learned at the workshop. This is one example of how a workshop experience can lead to better teaching practices through exposure to content material and current accepted practices in physics education research.

  2. Reactivity Initiated Accident Test Series RIA Scoping Test Experiment Operating Specification



    This document describes the experiment operating specifications for the Reactivity Initiated Accident (RIA) Scoping Test to be conducted in the Power Burst Facility (PBF) at the Idaho National Engineering Laboratory. The primary objectives of the RIA research are to determine fuel failure thresholds, modes, and consequences as functions of (a) enthalpy insertion, (b) irradiation history, and (c) fuel design. Coolant conditions of pressure, temperature, and flow rate that are typical of hot-startup conditions in commercial boiling water reactors (BWRs) will be used in the first six RIA tests, termed Series I.

  3. Initial experience with the Codman Certas adjustable valve in the management of patients with hydrocephalus

    Watt, Sara; Agerlin, Niels; Romner, Bertil


    A new adjustable valve, the Codman CertasTM valve for treatment of hydrocephalus was introduced into clinical practice in January 2011. It has 8 different settings with an opening pressure varying from 36 to over 400 mm H2O at a flow rate of 20 mL/h. The 8th setting is designed to provide...... a "virtual off" function. The objective of this report is to describe the initial clinical experience with the CertasTM valve and evaluate clinical usage with the main focus on the portable adjustment device - Therapeutic Management System (TMS), the "virtual off" setting and compatibility with magnetic...

  4. Sex reassignment surgery for male to female transsexuals: initial experience in Okayama university hospital.



    Full Text Available

    The first case of sex reassignment surgery (SRS in our hospital was performed in January 2001; as of February, 2005, 4 cases of MTF-SRS had been performed. In the 2 most recent cases, we used penile and scrotal skin flaps to avoid complications. The depth and width of the new vagina was made to be adequate for sexual intercourse. Future attention should be focused on devising a surgical technique that will help prevent the complications of partial necrosis of the epidermal skin and wound dehiscence. Although ours is only an initial experience, we describe our surgical technique herein.

  5. Current treatment of low grade gliomas

    M.J. van den Bent (Martin); T.A.B. Snijders (Tom); J.E.C. Bromberg (Jacolien)


    textabstractLow grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological fun

  6. Initial experience with stereoscopic visualization of three-dimensional ultrasound data in surgery.

    Gronningsaeter, A; Lie, T; Kleven, A; Mørland, T; Langø, T; Unsgård, G; Myhre, H O; Mårvik, R


    Initial in vivo and in vitro experiments were performed to evaluate the feasibility of stereoscopically displaying three-dimensional (3D) ultrasound data from neurosurgery, laparoscopic surgery, and vascular surgery. Stereoscopic visualization was illustrated by four video sequences, which can be downloaded from These sequences show a brain tumor, hepatic arteries in relation to the gallbladder, a model that mimics a neuroendoscope in a cyst, and a "flight" into model of an artery with an intima flap. The experiments indicate that stereoscopic display of ultrasound data is feasible when there is sufficient contrast between the objects of interest and the surrounding tissue. True 3D vision improves perception, thus enhancing the ability to understand complex anatomic structures such as irregular lesions and tortuous vessels.

  7. Comparison between initial Magnetized Liner Inertial Fusion experiments and integrated simulations

    Sefkow, A. B.; Gomez, M. R.; Geissel, M.; Hahn, K. D.; Hansen, S. B.; Harding, E. C.; Peterson, K. J.; Slutz, S. A.; Koning, J. M.; Marinak, M. M.


    The Magnetized Liner Inertial Fusion (MagLIF) approach to ICF has obtained thermonuclear fusion yields using the Z facility. Integrated magnetohydrodynamic simulations provided the design for the first neutron-producing experiments using capabilities that presently exist, and the initial experiments measured stagnation radii rstag < 75 μm, temperatures around 3 keV, and isotropic neutron yields up to YnDD = 2 ×1012 from imploded liners reaching peak velocities around 70 km/s over an implosion time of about 60 ns. We present comparisons between the experimental observables and post-shot degraded integrated simulations. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  8. A 12-week interdisciplinary rehabilitation trial in patients with gliomas – a feasibility study

    Hansen, Anders; Søgaard, Karen; Minet, Lisbeth Rosenbek


    %) was achieved at part one. However, the failure to meet predefined feasibility objectives of drop-out, adherence and patient satisfaction of the unsupervised intervention at part two have led to a protocol revision for a future randomized controlled trial. CONCLUSION: This study demonstrates that an intensive...... limitations in physical functioning, cognition, and emotional wellbeing. In a relatively small sample this study shows that supervised physical- and occupational therapy in patients with gliomas is safe and feasible in the initial treatment phase. Patients with gliomas can potentially improve functioning......PURPOSE: This report aims to assess the safety and feasibility of using an interdisciplinary rehabilitation intervention for a future randomized controlled trial in patients with gliomas in the initial treatment phase. METHOD: We conducted an outpatient two-part rehabilitation intervention...

  9. Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice.

    Friedmann-Morvinski, Dinorah; Bushong, Eric A; Ke, Eugene; Soda, Yasushi; Marumoto, Tomotoshi; Singer, Oded; Ellisman, Mark H; Verma, Inder M


    Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans. Here we show that gliomas can originate from differentiated cells in the central nervous system (CNS), including cortical neurons. Transduction by oncogenic lentiviral vectors of neural stem cells (NSCs), astrocytes, or even mature neurons in the brains of mice can give rise to malignant gliomas. All the tumors, irrespective of the site of lentiviral vector injection (the initiating population), shared common features of high expression of stem or progenitor markers and low expression of differentiation markers. Microarray analysis revealed that tumors of astrocytic and neuronal origin match the mesenchymal GBM subtype. We propose that most differentiated cells in the CNS upon defined genetic alterations undergo dedifferentiation to generate a NSC or progenitor state to initiate and maintain the tumor progression, as well as to give rise to the heterogeneous populations observed in malignant gliomas.

  10. Initial Off-Axis Neutral Beam Checkout and Physics Experiments on DIII-D

    van Zeeland, M. A.; Ferron, J. R.; Hyatt, A. W.; Murphy, C. J.; Petty, C. C.; Prater, R.; Scoville, J. T.; Heidbrink, W. W.; Muscatello, C. M.; Park, J. M.; Murakami, M.; Pace, D. C.; Holcomb, C. T.; Grierson, B. A.; Tobias, B. J.; Solomon, W. M.; Moyer, R. A.


    Two of the eight neutral beam sources on DIII-D have been modified to allow vertical steering, with the injection angle varying from horizontal to downward at an angle of 16.5 degrees for off-axis deposition. Initial experiments to assess the basic beam functionality, geometry, and confinement were carried out. Dα images of beam into gas and plasma yield beam neutral profiles and are key in assessing beam shape and clipping. Neutron and fast-ion Dα (FIDA) diagnostics verify classical behavior of the off-axis beam ions in MHD-quiescent conditions. An initial physics experiment takes advantage of the downward steered beams to vary the fast-ion gradient ∇βf from centrally peaked to hollow. Systematic scans determine the stability and impact of reversed shear Alfvén eigenmodes and toroidal Alfvén eigenmodes as a function of ∇βf . Supported by US DOE under DE-FC02-04ER54698, SC-G903402, DE-AC05-00OR22725, DE-AC05-06OR23100, DE-AC52-07NA27344, DE-AC02-09CH11466, & DE-FG02-07ER54917.

  11. Initial Experience with a Cone-beam Breast Computed Tomography-guided Biopsy System

    Seifert, Posy J; Morgan, Renee C; Conover, David L; Arieno, Andrea L


    Objective: To evaluate our initial experience with a cone-beam breast computed tomography (BCT)-guided breast biopsy system for lesion retrieval in phantom studies for use with a cone-beam BCT imaging system. Materials and Methods: Under the Institutional Review Board approval, a phantom biopsy study was performed using a dedicated BCT-guided biopsy system. Fifteen biopsies were performed on each of the small, medium, and large anthropomorphic breast phantoms with both BCT and stereotactic guidance for comparison. Each set of the 45 phantoms contained masses and calcification clusters of varying sizes. Data included mass/calcium retrieval rate and dose and length of procedure time for phantom studies. Results: Phantom mass and calcium retrieval rate were 100% for BCT and stereotactic biopsy. BCT dose for small and medium breast phantoms was found to be equivalent to or less than the corresponding stereotactic approach. Stereotactic-guided biopsy dose was 34.2 and 62.5 mGy for small and medium breast phantoms, respectively. BCT-guided biopsy dose was 15.4 and 30.0 mGy for small and medium breast phantoms, respectively. Both computed tomography biopsy and stereotactic biopsy study time ranged from 10 to 20 min. Conclusion: Initial experience with a BCT-guided biopsy system has shown to be comparable to stereotactic biopsy in phantom studies with equivalent or decreased dose. PMID:28217404

  12. Intraoperative 3-tesla MRI in the management of paediatric cranial tumours - initial experience

    Avula, Shivaram; Garlick, Deborah; Abernethy, Laurence J. [Alder Hey Children' s NHS Foundation Trust, Department of Radiology, Liverpool (United Kingdom); Mallucci, Connor L. [Alder Hey Children' s Hospital, Department of Neurosurgery, Liverpool (United Kingdom); Pizer, Barry [Alder Hey Children' s Hospital, Department of Oncology, Liverpool (United Kingdom); Crooks, Daniel [Walton Centre for Neurology and Neurosurgery, Department of Pathology, Liverpool (United Kingdom)


    Intraoperative MRI (ioMRI) has been gaining recognition because of its value in the neurosurgical management of cranial tumours. There is limited documentation of its value in children. To review the initial experience of a paediatric 3-Tesla ioMRI unit in the management of cranial tumours. Thirty-eight children underwent ioMRI during 40 cranial tumour resections using a 3-Tesla MR scanner co-located with the neurosurgical operating theatre. IoMRI was performed to assess the extent of tumour resection and/or to update neuronavigation. The intraoperative and follow-up scans, and the clinical records were reviewed. In 27/40 operations, complete resection was intended. IoMRI confirmed complete resection in 15/27 (56%). As a consequence, surgical resection was extended in 5/27 (19%). In 6/27 (22%), ioMRI was equivocal for residual tumour. In 13/40 (33%) operations, the surgical aim was to partially resect the tumour. In 7 of the 13 (54%), surgical resection was extended following ioMRI. In our initial experience, ioMRI has increased the rate of complete resection, with intraoperative surgical strategy being modified in 30% of procedures. Collaborative analysis of ioMRI by the radiologist and neurosurgeon is vital to avoid errors in interpretation. (orig.)

  13. The Model Parameter Estimation Experiment (MOPEX): Its structure, connection to other international initiatives and future directions

    Wagener, T; Hogue, T; Schaake, J; Duan, Q; Gupta, H; Andreassian, V; Hall, A; Leavesley, G


    The Model Parameter Estimation Experiment (MOPEX) is an international project aimed at developing enhanced techniques for the a priori estimation of parameters in hydrologic models and in land surface parameterization schemes connected to atmospheric models. The MOPEX science strategy involves: database creation, a priori parameter estimation methodology development, parameter refinement or calibration, and the demonstration of parameter transferability. A comprehensive MOPEX database has been developed that contains historical hydrometeorological data and land surface characteristics data for many hydrologic basins in the United States (US) and in other countries. This database is being continuously expanded to include basins from various hydroclimatic regimes throughout the world. MOPEX research has largely been driven by a series of international workshops that have brought interested hydrologists and land surface modelers together to exchange knowledge and experience in developing and applying parameter estimation techniques. With its focus on parameter estimation, MOPEX plays an important role in the international context of other initiatives such as GEWEX, PUB and PILPS. This paper outlines the MOPEX initiative, discusses its role in the scientific community and briefly states future directions.

  14. Initial Experiences of Simultaneous Laparoscopic Resection of Colorectal Cancer and Liver Metastases

    L. T. Hoekstra


    Full Text Available Introduction. Simultaneous resection of primary colorectal carcinoma (CRC and synchronous liver metastases (SLMs is subject of debate with respect to morbidity in comparison to staged resection. The aim of this study was to evaluate our initial experience with this approach. Methods. Five patients with primary CRC and a clinical diagnosis of SLM underwent combined laparoscopic colorectal and liver surgery. Patient and tumor characteristics, operative variables, and postoperative outcomes were evaluated retrospectively. Results. The primary tumor was located in the colon in two patients and in the rectum in three patients. The SLM was solitary in four patients and multiple in the remaining patient. Surgical approach was total laparoscopic (2 patients or hand-assisted laparoscopic (3 patients. The midline umbilical or transverse suprapubic incision created for the hand port and/or extraction of the specimen varied between 5 and 10 cm. Median operation time was 303 (range 151–384 minutes with a total blood loss of 700 (range 200–850 mL. Postoperative hospital stay was 5, 5, 9, 14, and 30 days. An R0 resection was achieved in all patients. Conclusions. From this initial single-center experience, simultaneous laparoscopic colorectal and liver resection appears to be feasible in selected patients with CRC and SLM, with satisfying short-term results.

  15. New perspectives on sea use management: initial findings from European experience with marine spatial planning.

    Douvere, Fanny; Ehler, Charles N


    Increased development pressures on the marine environment and the potential for multiple use conflicts, arising as a result of the current expansion of offshore wind energy, fishing and aquaculture, dredging, mineral extraction, shipping, and the need to meet international and national commitments to biodiversity conservation, have led to increased interest in sea use planning with particular emphasis on marine spatial planning. Several European countries, on their own initiative or driven by the European Union's Marine Strategy and Maritime Policy, the Bergen Declaration of the North Sea Conference, and the EU Recommendation on Integrated Coastal Zone Management, have taken global leadership in implementing marine spatial planning. Belgium, The Netherlands, and Germany in the North Sea, and the United Kingdom in the Irish Sea, have already completed preliminary sea use plans and zoning proposals for marine areas within their national jurisdictions. This paper discusses the nature and context of marine spatial planning, the international legal and policy framework, and the increasing need for marine spatial planning in Europe. In addition, the authors review briefly three marine spatial planning initiatives in the North Sea and conclude with some initial lessons learned from these experiences.

  16. Second Surgery in Insular Low-Grade Gliomas

    Tamara Ius


    Full Text Available Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs. Univariate analysis showed that TR is influenced by the following: extent of resection (EOR (P<0.002, ΔVT2T1 value (P<0.001, histological diagnosis of oligodendroglioma (P=0.017, and mutation of IDH1 (P=0.022. The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P<0.001. Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.

  17. The Lusi seismic experiment: An initial study to understand the effect of seismic activity to Lusi

    Karyono, E-mail: [Agency for Meteorology, Climatology and Geophysics (BMKG), Jakarta (Indonesia); OSLO University (Norway); Padjadjaran University (UNPAD), Bandung (Indonesia); Mazzini, Adriano; Sugiharto, Anton [OSLO University (Norway); Lupi, Matteo [ETH Zurich (Switzerland); Syafri, Ildrem [Padjadjaran University (UNPAD), Bandung (Indonesia); Masturyono,; Rudiyanto, Ariska; Pranata, Bayu; Muzli,; Widodo, Handi Sulistyo; Sudrajat, Ajat [Agency for Meteorology, Climatology and Geophysics (BMKG), Jakarta (Indonesia)


    The spectacular Lumpur Sidoarjo (Lusi) eruption started in northeast Java on the 29 of May 2006 following a M6.3 earthquake striking the island [1,2]. Initially, several gas and mud eruption sites appeared along the reactivated strike-slip Watukosek fault system [3] and within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. The Lusi seismic experiment is a project aims to begin a detailed study of seismicity around the Lusi area. In this initial phase we deploy 30 seismometers strategically distributed in the area around Lusi and along the Watukosek fault zone that stretches between Lusi and the Arjuno Welirang (AW) complex. The purpose of the initial monitoring is to conduct a preliminary seismic campaign aiming to identify the occurrence and the location of local seismic events in east Java particularly beneath Lusi.This network will locate small event that may not be captured by the existing BMKG network. It will be crucial to design the second phase of the seismic experiment that will consist of a local earthquake tomography of the Lusi-AW region and spatial and temporal variations of vp/vs ratios. The goal of this study is to understand how the seismicity occurring along the Sunda subduction zone affects to the behavior of the Lusi eruption. Our study will also provide a large dataset for a qualitative analysis of earthquake triggering studies, earthquake-volcano and earthquake-earthquake interactions. In this study, we will extract Green’s functions from ambient seismic noise data in order to image the shallow subsurface structure beneath LUSI area. The waveform cross-correlation technique will be apply to all of recordings of ambient seismic noise at 30 seismographic stations around the LUSI area. We use the dispersive behaviour of the retrieved Rayleigh waves to infer velocity structures in the shallow subsurface.

  18. The Lusi seismic experiment: An initial study to understand the effect of seismic activity to Lusi

    Karyono, Mazzini, Adriano; Lupi, Matteo; Syafri, Ildrem; Masturyono, Rudiyanto, Ariska; Pranata, Bayu; Muzli, Widodo, Handi Sulistyo; Sudrajat, Ajat; Sugiharto, Anton


    The spectacular Lumpur Sidoarjo (Lusi) eruption started in northeast Java on the 29 of May 2006 following a M6.3 earthquake striking the island [1,2]. Initially, several gas and mud eruption sites appeared along the reactivated strike-slip Watukosek fault system [3] and within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. The Lusi seismic experiment is a project aims to begin a detailed study of seismicity around the Lusi area. In this initial phase we deploy 30 seismometers strategically distributed in the area around Lusi and along the Watukosek fault zone that stretches between Lusi and the Arjuno Welirang (AW) complex. The purpose of the initial monitoring is to conduct a preliminary seismic campaign aiming to identify the occurrence and the location of local seismic events in east Java particularly beneath Lusi.This network will locate small event that may not be captured by the existing BMKG network. It will be crucial to design the second phase of the seismic experiment that will consist of a local earthquake tomography of the Lusi-AW region and spatial and temporal variations of vp/vs ratios. The goal of this study is to understand how the seismicity occurring along the Sunda subduction zone affects to the behavior of the Lusi eruption. Our study will also provide a large dataset for a qualitative analysis of earthquake triggering studies, earthquake-volcano and earthquake-earthquake interactions. In this study, we will extract Green's functions from ambient seismic noise data in order to image the shallow subsurface structure beneath LUSI area. The waveform cross-correlation technique will be apply to all of recordings of ambient seismic noise at 30 seismographic stations around the LUSI area. We use the dispersive behaviour of the retrieved Rayleigh waves to infer velocity structures in the shallow subsurface.

  19. Identification of proteins involved in neural progenitor cell targeting of gliomas

    Honeth Gabriella


    Full Text Available Abstract Background Glioblastoma are highly aggressive tumors with an average survival time of 12 months with currently available treatment. We have previously shown that specific embryonic neural progenitor cells (NPC have the potential to target glioma growth in the CNS of rats. The neural progenitor cell treatment can cure approximately 40% of the animals with malignant gliomas with no trace of a tumor burden 6 months after finishing the experiment. Furthermore, the NPCs have been shown to respond to signals from the tumor environment resulting in specific migration towards the tumor. Based on these results we wanted to investigate what factors could influence the growth and progression of gliomas in our rodent model. Methods Using microarrays we screened for candidate genes involved in the functional mechanism of tumor inhibition by comparing glioma cell lines to neural progenitor cells with or without anti-tumor activity. The expression of candidate genes was confirmed at RNA level by quantitative RT-PCR and at the protein level by Western blots and immunocytochemistry. Moreover, we have developed in vitro assays to mimic the antitumor effect seen in vivo. Results We identified several targets involved in glioma growth and migration, specifically CXCL1, CD81, TPT1, Gas6 and AXL proteins. We further showed that follistatin secretion from the NPC has the potential to decrease tumor proliferation. In vitro co-cultures of NPC and tumor cells resulted in the inhibition of tumor growth. The addition of antibodies against proteins selected by gene and protein expression analysis either increased or decreased the proliferation rate of the glioma cell lines in vitro. Conclusion These results suggest that these identified factors might be useful starting points for performing future experiments directed towards a potential therapy against malignant gliomas.

  20. Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma

    Kocher, M.; Kunze, S.; Eich, H.T.; Semrau, R.; Mueller, R.P. [Dept. of Radiation Oncology, Univ. of Cologne (Germany)


    Purpose: to evaluate the feasibility, safety and efficacy of daily temozolomide concurrent with postoperative radiotherapy in malignant glioma. Patients and methods: from 11/1999 to 03/2003, n = 81 patients aged 15-72 years (median 52 years, karnofsky score 80-100% in 83%) suffering from primary glioblastoma (n = 47), anaplastic astrocytoma (n = 6), anaplastic oligodendroglioma (n = 16), and recurrent glioma (n = 12) were treated. Patients with primary gliomas received a combination of postoperative radiotherapy (60 Gy/1.8- to 2.0-Gy fractions) and daily oral temozolomide (75 mg/m{sup 2}) at all irradiation days (30-33 doses), while recurrent tumors were treated with 45-60 Gy and temozolomide. Initially, 6/81 patients had daily temozolomide doses of 50 mg/m{sup 2}. Results: in total, 70/81 patients (86%) completed both radio- and chemotherapy. Grade 1 nausea/vomiting was seen in 28%, grade 2 in 11%, grade 3 in 1%. Antiemetics were applied in 41%. Hematologic toxicities were observed as follows: leukopenia grade 3/4 1%, lymphopenia grade 3/4 46%, thrombopenia grade 3/4 1%. Two patients under dexamethasone suffered herpes encephalitis after one and 16 doses of temozolomide (75 mg/m{sup 2}). Median survival was 15 months for glioblastoma. In oligodendroglioma patients, a 4-year survival rate of 78% was observed. Conclusion: postoperative radiochemotherapy with 30-33 daily doses of temozolomide (75 mg/m{sup 2}) is safe in patients with malignant glioma. The combined schedule is effective in oligodendroglioma patients and may prolong survival in glioblastoma. Effort should be taken to minimize corticosteroid doses, since both steroids and temozolomide lead to immunosuppression. (orig.)

  1. Involvement of the kynurenine pathway in human glioma pathophysiology.

    Seray Adams

    Full Text Available The kynurenine pathway (KP is the principal route of L-tryptophan (TRP catabolism leading to the production of kynurenine (KYN, the neuroprotectants, kynurenic acid (KYNA and picolinic acid (PIC, the excitotoxin, quinolinic acid (QUIN and the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+. The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1, indoleamine 2,3-dioxygenase-2 (IDO-2 and tryptophan 2,3-dioxygenase (TDO-2 initiate the first step of the KP. IDO-1 and TDO-2 induction in tumors are crucial mechanisms implicated to play pivotal roles in suppressing anti-tumor immunity. Here, we report the first comprehensive characterisation of the KP in 1 cultured human glioma cells and 2 plasma from patients with glioblastoma (GBM. Our data revealed that interferon-gamma (IFN-γ stimulation significantly potentiated the expression of the KP enzymes, IDO-1 IDO-2, kynureninase (KYNU, kynurenine hydroxylase (KMO and significantly down-regulated 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD and kynurenine aminotransferase-I (KAT-I expression in cultured human glioma cells. This significantly increased KP activity but significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. KP activation (KYN/TRP was significantly higher, whereas the concentrations of the neuroreactive KP metabolites TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18 compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+, which is necessary for energy production and DNA repair.

  2. TRPM7 channels regulate glioma stem cell through STAT3 and Notch signaling pathways.

    Liu, Mingli; Inoue, Koichi; Leng, Tiandong; Guo, Shanchun; Xiong, Zhi-gang


    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults with median survival time of 14.6 months. A small fraction of cancer stem cells (CSC) initiate and maintain tumors thus driving glioma tumorigenesis and being responsible for resistance to classical chemo- and radio-therapies. It is desirable to identify signaling pathways related to CSC to develop novel therapies to selectively target them. Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7 is a ubiquitous, Ca(2+) and Mg(2+) permeable ion channels that are special in being both an ion channel and a serine/threonine kinase. In studies of glioma cells silenced for TRPM7, we demonstrated that Notch (Notch1, JAG1, Hey2, and Survivin) and STAT3 pathways are down regulated in glioma cells grown in monolayer. Furthermore, phospho-STAT3, Notch target genes and CSC markers (ALDH1 and CD133) were significantly higher in spheroid glioma CSCs when compared with monolayer cultures. The results further show that tyrosine-phosphorylated STAT3 binds and activates the ALDH1 promoters in glioma cells. We found that TRMP7-induced upregulation of ALDH1 expression is associated with increases in ALDH1 activity and is detectable in stem-like cells when expanded as spheroid CSCs. Finally, TRPM7 promotes proliferation, migration and invasion of glioma cells. These demonstrate that TRPM7 activates JAK2/STAT3 and/or Notch signaling pathways and leads to increased cell proliferation and migration. These findings for the first time demonstrates that TRPM7 (1) activates a previously unrecognized STAT3→ALDH1 pathway, and (2) promotes the induction of ALDH1 activity in glioma cells.

  3. Bromelain reversibly inhibits invasive properties of glioma cells.

    Tysnes, B B; Maurer, H R; Porwol, T; Probst, B; Bjerkvig, R; Hoover, F


    Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, and fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, and invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that alpha3 and beta1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE-mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, and translational attenuation.

  4. Bromelain Reversibly Inhibits Invasive Properties of Glioma Cells

    Berit B. Tysnes


    Full Text Available Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that a3 and α1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE-mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, translational attenuation.

  5. The engineered Salmonella typhimurium inhibits tumorigenesis in advanced glioma

    Chen JQ


    Full Text Available Jian-qiang Chen,1 Yue-fu Zhan,2 Wei Wang,1 Sheng-nan Jiang,2,3 Xiang-ying Li21Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Radiology, Affiliated to Haikou Hospital Xiangya School of Medicine, Central South University, Haikou, People’s Republic of China; 3Department of Nuclear Medicine, Central South University Xiangya School of Medicine Affiliated HaiKou Hospital, Haikou, Hainan, People’s Republic of ChinaObjective: To explore the antitumor role of the attenuated Salmonella typhimurium ΔppGpp with inducible cytolysin A (ClyA in advanced stage of glioma.Materials and methods: The C6 rat glioma cells were orthotopically implanted by surgery into the caudate nucleus of rat brains. The rats were then randomly divided into the treatment group (SL + ClyA (n=12, negative control group (SL (n=12, and control group (phosphate-buffered saline [PBS] (n=12. In the treatment group, the attenuated S. typhimurium were transformed with the plasmid-encoded antitumor gene ClyA. The expression of ClyA was controlled by the TetR-regulated promoter in response to extracellular doxycycline. The plasmid also contained an imaging gene lux to allow illumination of the tumor infected by the bacteria. The rat glioma C6 cells were implanted into the caudate nucleus of all rats. The engineered S. typhimurium and respective controls were injected intravenously into the rats 21 days after initial tumor implantation. The pathological analysis of the glioma tumor was performed at 21 days and 28 days (7 days after doxycycline treatment postimplantation. All rats underwent MRI (magnetic resonance imaging and bioluminescence study at 21 days and 28 days postimplantation to detect tumor volume. The differences between the three groups in tumor volume and survival time were analyzed.Results: Advanced stage glioma  was detected at 21 days postimplantation. Bioluminescence showed that the

  6. Statistical evaluation of manual segmentation of a diffuse low-grade glioma MRI dataset.

    Ben Abdallah, Meriem; Blonski, Marie; Wantz-Mezieres, Sophie; Gaudeau, Yann; Taillandier, Luc; Moureaux, Jean-Marie


    Software-based manual segmentation is critical to the supervision of diffuse low-grade glioma patients and to the optimal treatment's choice. However, manual segmentation being time-consuming, it is difficult to include it in the clinical routine. An alternative to circumvent the time cost of manual segmentation could be to share the task among different practitioners, providing it can be reproduced. The goal of our work is to assess diffuse low-grade gliomas' manual segmentation's reproducibility on MRI scans, with regard to practitioners, their experience and field of expertise. A panel of 13 experts manually segmented 12 diffuse low-grade glioma clinical MRI datasets using the OSIRIX software. A statistical analysis gave promising results, as the practitioner factor, the medical specialty and the years of experience seem to have no significant impact on the average values of the tumor volume variable.

  7. Post-game analysis: An initial experiment for heuristic-based resource management in concurrent systems

    Yan, Jerry C.


    In concurrent systems, a major responsibility of the resource management system is to decide how the application program is to be mapped onto the multi-processor. Instead of using abstract program and machine models, a generate-and-test framework known as 'post-game analysis' that is based on data gathered during program execution is proposed. Each iteration consists of (1) (a simulation of) an execution of the program; (2) analysis of the data gathered; and (3) the proposal of a new mapping that would have a smaller execution time. These heuristics are applied to predict execution time changes in response to small perturbations applied to the current mapping. An initial experiment was carried out using simple strategies on 'pipeline-like' applications. The results obtained from four simple strategies demonstrated that for this kind of application, even simple strategies can produce acceptable speed-up with a small number of iterations.

  8. Use of indocyanine green angiography in microsurgical subinguinal varicocelectomy - lessons learned from our initial experience.

    Cho, Chak-Lam; Ho, Kwan-Lun; Chan, Wayne Kwun-Wai; Chu, Ringo Wing-Hong; Law, In-Chak


    Microsurgical subinguinal varicocelectomy (MSV) is generally considered the gold standard nowadays in view of the lower risk of complications and recurrence. To achieve complete ligation of veins while preserving testicular artery (TA) during the procedure remains challenging despite the application of high power optical magnification and micro-Doppler ultrasonography. The use of intraoperative indocyanine green angiography (ICGA) with infrared fluorescence operative micro-scope in MSV potentially lowers the incidence of TA injury and shortens the learning curve of nov-ice surgeons. We present our initial experience in the application of the technique in nine patients and explore the potential of the new adjunct. Copyright® by the International Brazilian Journal of Urology.

  9. The Case For Reporting Pro-Active Environmental Initiatives: A Malaysian Experiment On Stakeholder Influence Strategies

    Evangeline Elijido-Ten


    Full Text Available The purpose of this research is to gain insights on the preferred strategies chosen by various stakeholder representatives to influence management to either provide/not provide environmental disclosures in an experimental setting. A typology of resource relationships and influence strategies is adapted as a framework to make sense of the views presented by various stakeholder representative groups. To facilitate a Malaysian experiment, qualitative interviews with the aid of a hypothetical vignette are conducted to understand how different stakeholder groups go about seeking what they want from the management. The findings in this exploratory study indicate that although the model is useful to understand the influence strategies taken by each stakeholder group, its effectiveness is tempered by the level of significance placed by these groups on the environmental initiative and their perception of how the event will affect their stake on the firm.

  10. Highlight report local initiatives. Experiences with electric transport; Highlight report lokale initiatieven. Ervaringen met elektrisch vervoer



    In March 2013 Linkingreen and XTNT started a survey on local electric transportation initiatives. The aim is to learn from the experiences, problems and obstacles of business users of electric vehicles: cars, vans or trucks, scooters, boats and special vehicles (e.g. garbage trucks) that are all-electric or plug-in (with plug). In this brief report, the main results are presented [Dutch] In maart 2013 is door Linkingreen en XTNT in opdracht van Agentschap NL een enquete uitgezet naar lokale initiatieven elektrisch vervoer. Doel is te leren wat de ervaringen, knelpunten en belemmeringen zijn van zakelijke gebruikers van elektrisch vervoer: personenauto's, bestel- of vrachtauto's, scooters, vaartuigen en bijzondere voertuigen (vuilniswagens etc.) die volledig elektrische of plug in (met stekker) zijn. In dit korte verslag zijn de belangrijkste resultaten opgenomen.


    Vandersall, K S; Tarver, C M; Garcia, F; Chidester, S; Urtiew, P A; Forbes, J W


    Shock initiation experiments were performed on the plastic bonded explosive (PBX) LX-04 (85% HMX, 15% Viton binder) using single and multiple low amplitude shocks to obtain pressure history data for use in Ignition and Growth reactive flow modeling parameterization. A 100 mm diameter propellant driven gas gun was utilized to initiate the LX-04 explosive charges containing manganin piezoresistive pressure gauge packages placed between explosive discs. In the single shock experiments, the run distances to detonation at three shock pressures showed agreement with previously published data above 3 GPa. Even longer run distances to detonation were measured using 80 mm long by 145 mm diameter LX-04 charges impacted by low velocity projectiles from a 155 mm diameter gun. The minimum shock pressure required to cause low levels of exothermic reaction were determined for these large LX-04 charge dimensions. Multiple shocks were generated as double shocks by using a flyer plate with two materials and as reflected shocks by placing a high impedance material at the rear of the explosive charge. In both cases, the first shock pressure was not high enough to cause detonation of LX-04, and the second shock pressure, which would have been sufficient to cause detonation if generated by a single shock, failed to cause detonation. Thus LX-04 exhibited shock desensitization over a range of 0.6 to 1.4 GPa. The higher shock pressure LX-04 model was extended to accurately simulate these lower pressure and multiple shock gauge records. The shock desensitization effects observed with multiple shock compressions were partially accounted for in the model by using a critical compression corresponding to a shock pressure of 1.2 GPa. This shock desensitization effect occurs at higher pressures than those of other HMX-based PBX's containing higher HMX percentages.

  12. Initial experience of using the filter protection device during carotid artery stenting in Japan.

    Takayama, Katsutoshi; Nakagawa, Hiroyuki; Iwasaki, Satoru; Taoka, Toshiaki; Miyasaka, Toshiteru; Myouchin, Kaoru; Wada, Takeshi; Sakamoto, Masahiko; Fukusumi, Akio; Nakagawa, Ichiro; Kurokawa, Shinichiro; Kichikawa, Kimihiko


    No filter protection devices for carotid artery stenting (CAS) have been formally approved for use in Japan; however, as of April 2008, the Angioguard XP (AGXP) was approved. This article describes our initial results using the AGXP during CAS for the treatment of carotid artery stenosis. A group of 15 patients (14 men) with a mean age of 72.3 years (range 53-81 years) were treated by CAS using the AGXP. Among them, 10 were symptomatic with >50% stenosis of the common or internal carotid artery (ICA), and 5 were asymptomatic with >70% stenosis. The rates of technical success, periprocedural stroke, ICA flow impairment, filter movement, and development of new ischemic lesions on diffusion-weighted imaging (DWI) were assessed. CAS using the AGXP was successful in all cases. There was one minor stroke, and flow impairment occurred in six patients. Filter movement averaged 1.9 vertebral bodies. DWI showed new ipsilateral ischemic lesions in eight of the patients. Initial clinical experience using the AGXP for CAS has been generally sufficient. However, attention must be paid to three problems when using the AGXP: the filter may move after placement; the filter may disturb blood flow in the ICA; and debris may pass around the filter.

  13. Endobronchial Ultrasound-directed Transbronchial Needle Aspiration in Diagnosis of Mediastinal Lesions: Initial Egyptian Experience.

    Safwat, Tarek; Khattab, Adel; Haddad, Salwa El; Mostafa, Yasser; Korraa, Emad; Madkour, Ashraf; Fattah, Wael Abd El


    Mediastinal lesions represent a diagnostic challenge and often require invasive approaches. We evaluated the role of radial probe endobronchial ultrasound-directed transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal lesions. Between March 2005 to February 2006, 30 consecutive patients with enlarged mediastinal lymph nodes from unknown etiologies or suspicious for metastatic bronchogenic carcinoma and mediastinal masses underwent EBUS-TBNA and were clinically followed up. EBUS-TBNA was applied under topical anesthesia, midazolam sedation with a mean dose of 4.6+1.7 mg and prolonged the examination by 14.7 minutes on average. EBUS-directed TBNA was performed in 17 lymph nodes and 13 mediastinal masses, achieving specific diagnosis in 82.3% (14/17) and 84.6% (11/13) of examined lesions, respectively, with an overall yield of 83%. The sensitivity, specificity, and accuracy of EBUS-TBNA in distinguishing benign from malignant mediastinal lesions were 89.4%, 100%, and 93.3%, respectively. EBUS was well tolerated by most of the patients with no TBNA-related complications. In conclusion, EBUS-TBNA of mediastinal lesions is a minimally invasive safe diagnostic technique with high yield, even in the hands of those with initial experience. This initial study is convincing and stimulating for widespread application of EBUS-TBNA in Egyptian bronchoscopy practice.

  14. Academics and Learners’ Perceptions on Blended Learning as a Strategic Initiative to Improve Student Learning Experience

    Ying Adeline Ng Ling


    Full Text Available The increasingly tighter shift of socio-economic constraints on higher education sectors in the recent years has called for greater flexibilities in student learning experience both locally and abroad. To this end, we have recently implemented a Blended Learning Initiative in an attempt to provide better learning support and greater flexibility to our students. This initiative is also in line with the University’s aim of having 50% of our learning and teaching delivered on-line by 2020. In this report, we present our findings on academics and learners’ perceptions on the approach which were obtained through surveys. Results showed that blended learning approach was new to the academics and the factors for successful blended learning implementation were identified. Results also showed that learners appreciated the approach as it made learning more accessible and flexible. Furthermore, they also enjoyed the interesting online activities incorporated into their units. In addition, learners were also able to review and pace their own learning. They also perceived that they have the access to the resources and technical ability to cope with online learning materials and activities. Nonetheless, the survey also revealed that learners still prefer to have academics delivering information to them directly rather than a flipped classroom model. In conclusion, findings from this study provide insights that blended learning could be effective to supplement courses offered by the faculty.

  15. Implementation of electronic checklists in an oncology medical record: initial clinical experience.

    Albuquerque, Kevin V; Miller, Alexis A; Roeske, John C


    The quality of any medical treatment depends on the accurate processing of multiple complex components of information, with proper delivery to the patient. This is true for radiation oncology, in which treatment delivery is as complex as a surgical procedure but more dependent on hardware and software technology. Uncorrected errors, even if small or infrequent, can result in catastrophic consequences for the patient. We developed electronic checklists (ECLs) within the oncology electronic medical record (EMR) and evaluated their use and report on our initial clinical experience. Using the Mosaiq EMR, we developed checklists within the clinical assessment section. These checklists are based on the process flow of information from one group to another within the clinic and enable the processing, confirmation, and documentation of relevant patient information before the delivery of radiation therapy. The clinical use of the ECL was documented by means of a customized report. Use of ECL has reduced the number of times that physicians were called to the treatment unit. In particular, the ECL has ensured that therapists have a better understanding of the treatment plan before the initiation of treatment. An evaluation of ECL compliance showed that, with additional staff training, > 94% of the records were completed. The ECL can be used to ensure standardization of procedures and documentation that the pretreatment checks have been performed before patient treatment. We believe that the implementation of ECLs will improve patient safety and reduce the likelihood of treatment errors.

  16. Platelet-derived growth factor receptor alpha in glioma: a bad seed

    Kun-Wei Liu; Bo Hu; Shi-Yuan Cheng


    Recent collaborative,large-scale genomic profiling of the most common and aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced our understanding of this disease.The gene encoding platelet-derived growth factor receptor alpha (PDGFRα) was identified as the third of the top 11 amplified genes in clinical GBM specimens.The important roles of PDGFRα signaling during normal brain development also implicate the possible pathologic consequences of PDGFRα over-activation in glioma.Although the initial clinical trials using PDGFR kinase inhibitors have been predominantly disappointing,diagnostic and treatment modalities involving genomic profiling and personalized medicine are expected to improve the therapy targeting PDGFRα signaling.In this review,we discuss the roles of PDGFRα signaling during development of the normal central nervous system (CNS) and in pathologic conditions such as malignant glioma.We further compare various animal models of PDGF-induced gliomagenesis and their potential as a novel platform of pre-clinical drug testing.We then summarize our recent publication and how these findings will likely impact treatments for gliomas driven by PDGFRα overexpression.A better understanding of PDGFRα signaling in glioma and their microenvironment,through the use of human or mouse models,is necessary to design a more effective therapeutic strategy against gliomas harboring the aberrant PDGFRα signaling.

  17. Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells

    Dah-Yuu Lu


    Full Text Available Glioma is the most common primary adult brain tumor with poor prognosis because of the ease of spreading tumor cells to other regions of the brain. Cell apoptosis is frequently targeted for developing anti-cancer drugs. In the present study, we have assessed wogonin, a flavonoid compound isolated from Scutellaria baicalensis Georgi, induced ROS generation, endoplasmic reticulum (ER stress and cell apoptosis. Wogonin induced cell death in two different human glioma cells, such as U251 and U87 cells but not in human primary astrocytes (IC 50 > 100 μM. Wogonin-induced apoptotic cell death in glioma cells was measured by propidine iodine (PI analysis, Tunnel assay and Annexin V staining methods. Furthermore, wogonin also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Moreover, treatment of wogonin also increased a number of signature ER stress markers glucose-regulated protein (GRP-78, GRP-94, Calpain I, and phosphorylation of eukaryotic initiation factor-2α (eIF2α. Treatment of human glioma cells with wogonin was found to induce reactive oxygen species (ROS generation. Wogonin induced ER stress-related protein expression and cell apoptosis was reduced by the ROS inhibitors apocynin and NAC (N-acetylcysteine. The present study provides evidence to support the fact that wogonin induces human glioma cell apoptosis mediated ROS generation, ER stress activation and cell apoptosis.

  18. Single-session Gamma Knife radiosurgery for optic pathway/hypothalamic gliomas.

    El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M


    OBJECTIVE Because of their critical and central location, it is deemed necessary to fractionate when considering irradiating optic pathway/hypothalamic gliomas. Stereotactic fractionated radiotherapy is considered safer when dealing with gliomas in this location. In this study, the safety and efficacy of single-session stereotactic radiosurgery for optic pathway/hypothalamic gliomas were reviewed. METHODS Between December 2004 and June 2014, 22 patients with optic pathway/hypothalamic gliomas were treated by single-session Gamma Knife radiosurgery. Twenty patients were available for follow-up for a minimum of 1 year after treatment. The patients were 5 to 43 years (median 16 years) of age. The tumor volume was 0.15 to 18.2 cm(3) (median 3.1 cm(3)). The prescription dose ranged from 8 to 14 Gy (median 11.5 Gy). RESULTS The mean follow-up period was 43 months. Five tumors involved the optic nerve only, and 15 tumors involved the chiasm/hypothalamus. Two patients died during the follow-up period. The tumors shrank in 12 cases, remained stable in 6 cases, and progressed in 2 cases, thereby making the tumor control rate 90%. Vision remained stable in 12 cases, improved in 6 cases, and worsened in 2 cases in which there was tumor progression. Progression-free survival was 83% at 3 years. CONCLUSIONS The initial results indicate that single-session Gamma Knife radiosurgery is a safe and effective treatment option for optic pathway/hypothalamic gliomas.

  19. Epidermal growth factor receptor:a key manipulator in molecular pathways of malignant glioma

    Changshu Ke


    The epidermal growth factor receptor (EGFR) is a member of the ErbB/EGFR family, including EGFR/Her1, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its efects through the receptor tyrosine kinase phosphorylation and activation of important downstream signaling pathways in normal and neoplastic cels, mainly the Ras GTPase/MAP kinase (MAPK), STAT3, and phosphatidylinositide 3 kinase-AKT pathways. EGFR deregulation is common in malignant glioma, especialy primary glioblastoma, and exists in three forms: gene overexpression (amplification), autocrine efects of EGFR activation, and activating receptor mutation (EGFRvIII). However, some EGFR abnormalities have also been found in low-grade gliomas, including the nuclear localization of EGFR, expression in the microfoci of anaplastic transformation, and association with neovascularization in the mesenchyma of the glioma, which suggests that some unknown EGFR-related mechanisms are possibly responsible for its central role in the initiation and progression of malignant glioma. Uncovering these mechanisms wil have potential value in the development of radio-therapy, chemotherapy, and EGFR-targeted therapy for glioma.

  20. A drosophila model for EGFR-Ras and PI3K-dependent human glioma.

    Renee D Read


    Full Text Available Gliomas, the most common malignant tumors of the nervous system, frequently harbor mutations that activate the epidermal growth factor receptor (EGFR and phosphatidylinositol-3 kinase (PI3K signaling pathways. To investigate the genetic basis of this disease, we developed a glioma model in Drosophila. We found that constitutive coactivation of EGFR-Ras and PI3K pathways in Drosophila glia and glial precursors gives rise to neoplastic, invasive glial cells that create transplantable tumor-like growths, mimicking human glioma. Our model represents a robust organotypic and cell-type-specific Drosophila cancer model in which malignant cells are created by mutations in signature genes and pathways thought to be driving forces in a homologous human cancer. Genetic analyses demonstrated that EGFR and PI3K initiate malignant neoplastic transformation via a combinatorial genetic network composed primarily of other pathways commonly mutated or activated in human glioma, including the Tor, Myc, G1 Cyclins-Cdks, and Rb-E2F pathways. This network acts synergistically to coordinately stimulate cell cycle entry and progression, protein translation, and inappropriate cellular growth and migration. In particular, we found that the fly orthologs of CyclinE, Cdc25, and Myc are key rate-limiting genes required for glial neoplasia. Moreover, orthologs of Sin1, Rictor, and Cdk4 are genes required only for abnormal neoplastic glial proliferation but not for glial development. These and other genes within this network may represent important therapeutic targets in human glioma.

  1. The Effects of a Midbrain Glioma on Memory and Other Functions: A Longitudinal Single Case Study

    Weddell, Rodger A.


    Our understanding of the effects of midbrain damage on cognition is largely based on animal studies, though there have been occasional investigations of the effects of human midbrain lesions on cognition. This investigation of a rare case of a glioma initially confined to the dorsal midbrain explores the effects of disease progression on IQ,…

  2. Magnetic paclitaxel nanoparticles inhibit glioma growth and improve the survival of rats bearing glioma xenografts.

    Zhao, Ming; Liang, Chao; Li, Anmin; Chang, Jin; Wang, Hanjie; Yan, Runmin; Zhang, Jiajing; Tai, Junli


    Paclitaxel has fared poorly in clinical trials against brain glioma. We hypothesized that superparamagnetic nanocarriers may enhance its bioactivities by delivering it into the brain. The magnetic paclitaxel nanoparticles (MPNPs) were fabricated and their cytotoxicity against glioma was tested both in vitro and in glioma-bearing rats. MPNPs exhibited superparamagnetism and produced an extended release of paclitaxel over 15 days in vitro. They were easily internalized into glioma cells and exerted remarkable toxicity, as free paclitaxel did. Furthermore, after intravenous injection of MPNPs to glioma-bearing rats and magnetic targeting with a 0.5 T magnet, drug content increased for 6- to 14-fold in implanted glioma and 4.6- to 12.1-fold in the normal brain compared to free paclitaxel. The survival of glioma-bearing rats was significantly prolonged after magnetic targeting therapy with MPNPs. MPNPs efficiently delivered paclitaxel into brain glioma by magnetic targeting and enhance its antitumor activity. They are promising for local chemotherapy for malignant glioma.

  3. Microcosm experiments to study the interaction of solid and solute phases during initial soil development

    Zimmermann, C.; Chabbi, S.; Schaaf, W.


    During the initial phase of soil formation mineral weathering, interactions between the solid and liquid phases as well as accumulation of organic matter play an important role for the development of soil properties and for the establishment of vegetation and the colonization of soil biota. Our study is part of the Transregional Collaborative Research Centre (SFB/TRR 38) ‘Patterns and processes of initial ecosystem development in an artificial catchment' funded by the Deutsche Forschungsgemeinschaft (DFG). The catchment ´Chicken Creeḱ close to Cottbus (Germany) has a size of 6 ha and is composed of a 3-4 m layer of Quaternary loamy to sandy sediments overlying a 1-2 m clay layer. To connect interactions between the soil solid phase and soil solution at the micro-scale with observed processes at the catchment scale we perform microcosm experiments with soil samples from the catchment under controlled laboratory conditions. The microcosm experiments are carried out in a climate chamber at constant 10 °C corresponding to the mean annual temperature of the region. In total 48 soil columns with a diameter of 14.4 cm and height of 30 cm were filled with substrates of two textural compositions reflecting the gradients observed at the catchment and a bulk density of 1.4-1.5 g*cm3. Within the microcosms it is possible to control the gaseous phase and the water fluxes by artificial irrigation. The irrigation runs automated and quasi-continuously four times a day with 6.6 ml each (in total 600 mm*yr-1). Irrigation amount and chemical composition of the artificial rainwater are based on the annual mean at the field site. Litter of two different plant species occurring at the catchment site (Lotus corniculatus, Calamagrostis epigejos) labelled with stable isotopes (δ13C; δ15N) is used for the experiments. All treatments including a control run with four replicates. The gaseous phase in the headspace of the microcosms is analysed continuously for CO2 and N2O contents

  4. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta [G. d' Annunzio Univ. of Chieti, SS. Annunziata Hospital, Chieti (Italy). Dept. of Radiation Oncology; Buonaguidi, Roberto [G. d' Annunzio Univ. of Chieti, Spirito Santo Hospital, Pescara (Italy). Dept. of Neurosurgery; Galzio, Renato J. [Univ. of L' Aquila, San Salvatore Hospital, L' Aquila (Italy). Dept. of Operative Unit of Neurosurgery and Health Sciences; Di Nicola, Marta [G. d' Annunzio Univ. of Chieti (Italy). Lab. of Biostatistics


    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level {<=} 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level {<=} 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  5. Gamma Knife treatment of low-grade gliomas in children.

    Ekşi, Murat Şakir; Yılmaz, Baran; Akakın, Akın; Toktaş, Zafer Orkun; Kaur, Ahmet Cemil; Demir, Mustafa Kemal; Kılıç, Türker


    Low-grade gliomas have good overall survival rates in pediatric patients compared to adults. There are some case series that reported the effectiveness and safety of Gamma Knife radiosurgery, yet they are limited in number of patients. We aimed to review the relevant literature for pediatric low-grade glial tumors treated with stereotactic radiosurgery, specifically Gamma Knife radiosurgery, and to present an exemplary case. A 6-year-old boy was admitted to clinic due to head trauma. He was alert, cooperative, and had no obvious motor or sensorial deficit. A head CT scan depicted a hypodense zone at the right caudate nucleus. The brain magnetic resonance imaging (MRI) depicted a mass lesion at the same location. A stereotactic biopsy was performed. Histopathological diagnosis was low-grade astrocytoma (grade II, World Health Organization (WHO) classification, 2007). Gamma Knife radiosurgery was applied to the tumor bed. Tumor volume was 21.85 cm(3). Fourteen gray was given to 50% isodose segment of the lesion (maximal dose of 28 Gy). The tumor has disappeared totally in 4 months, and the patient was tumor-free 21 months after the initial treatment. The presented literature review represents mostly single-center experiences with different patient and treatment characteristics. Accordingly, a mean/median margin dose of 11.3-15 Gy with Gamma Knife radiosurgery (GKRS) is successful in treatment of pediatric and adult low-grade glial tumor patients. However, prospective studies with a large cohort of pediatric patients should be conducted to make a more comprehensive conclusion for effectiveness and safety of GKRS in pediatric low-grade glial tumors.

  6. Optic Pathway Gliomas in Neurofibromatosis 1 (NF-1

    J Gordon Millichap


    Full Text Available Advances in the pathophysiology and clinical behavior of NF-1 associated optic pathway gliomas (OPG made over the past 10 years are examined, and evidence-based recommendations for diagnosis and management are proposed by researchers from Children's Memorial Hospital, Chicago; St Thomas's Hospital, London; Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia; and Washington University School of Medicine, St Louis, MO, The initial diagnostic and management guidelines proposed by a task force in 1997 are extended, and unanswered questions are addressed.

  7. Long non-coding RNA ENST00462717 suppresses the proliferation, survival, and migration by inhibiting MDM2/MAPK pathway in glioma.

    Wang, Aiqin; Meng, Mingzhu; Zhao, Xiuhe; Kong, Lina


    Gliomas are the most common and aggressive primary malignant tumor in the central nervous system, and requires new biomarkers and therapeutic methods. Long noncoding RNAs (lncRNAs) are important factors in numerous human diseases, including cancer. But studies on lncRNAs and gliomas are limited. In this study, we investigated the expression patterns of lncRNAs in 3 pairs of glioma samples and adjacent non-tumor tissues via microarray and selected the most down-regulated lnc00462717 to further verify its roles in glioma. We observed that decreased lnc00462717 expression was associated with the malignant status in glioma. In vitro experiment demonstrated that lnc00462717 overexpression suppressed glioma cell proliferation, survival and migration while knockdown of lnc00462717 had an opposite result. Moreover, we identified MDM2 as a direct target of lnc00462717 and lnc00462717 played a role by partially regulating the MDM2/MAPK pathway. In conclusion, lnc00462717 may function in suppressing glioma cell proliferation, survival, migration and may potentially serve as a novel biomarker and therapeutic target for glioma.

  8. TRIM28 as an independent prognostic marker plays critical roles in glioma progression.

    Qi, Zeng-Xin; Cai, Jia-Jun; Chen, Ling-Chao; Yue, Qi; Gong, Yan; Yao, Yu; Mao, Ying


    Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glioma controls (n = 6). TRIM28 expression was positively correlated with tumor malignancy, and associated with poor overall survival (OS) and progression-free survival (PFS). Notably, TRIM28 expression was negatively correlated with p21 expression in patients with glioblastoma multiforme (GBM). A multivariate analysis that included relevant measures indicated that high TRIM28 expression is an independent prognostic factor for poor OS and PFS in GBM patients. In experiments with cultured glioma cells, down-regulating TRIM28 with shRNA increased p21 expression, and induced cell cycle arrest at the G1 phase. In a xenograft model, down-regulating TRIM28 suppressed tumor growth. These results indicate that over-expression of TRIM28 is associated with poor outcome in glioma patients.

  9. Adult high-grade malignant gliomas

    Fable Zustovich


    Full Text Available Central nervous system (CNS malignant gliomas are relatively rare diseases. Prognosis is poor but has improved over recent years due to the improvement in the multi-disciplinary treatment: surgery, radiotherapy and chemotherapy...

  10. Targeting immune checkpoints in malignant glioma

    Li, Tete; Liu, Yong-Jun; Chen, Wei; Chen, Jingtao


    Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the bodys anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered immune privileged and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma. In this review, we focus on immune checkpoint inhibitors, specifically, antagonizing monoclonal antibodies for programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO). We discuss advances in the working mechanisms of these immune checkpoint molecules, their status in malignant glioma, and current preclinical and clinical trials targeting these molecules in malignant glioma. PMID:27756892

  11. Effect of Microgravity on Sinorhizobium meliloti: Initial Results from the SyNRGE Experiment

    Roberts, Michael S.; Stutte, Gary W.


    SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIe) hardware to study the effect of microgravity on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species of the legume family, was innoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early events associated with infection and nodulation in Petri Dish Fixation Units (PDFUs). Two sets of experiments were conducted in orbit and in 24-hour delayed ground controls. Experiment one was designed to determine if S. meliloti infect M. truncatula and initiate physiological changes associated with nodule formation. Roots of five-day-old M. truncatula cultivar Jemalong A17 (Enodll::gus) were innoculated 24 hr before launch with either S. meliloti strain 1021 or strain ABS7 and integrated into BRIC-PDFU hardware placed in a 4 C Cold Bag for launch on Atlantis. Innoculated plants and uninoculated controls were maintained in the dark at ambient temperature in the middeck of STS-135 for 11 days before fixation in RNA/ate/M by crew activation of the PDFU. Experiment two was designed to determine if microgravity altered the process of bacterial infection and host plant nodule formation. Seeds of two M. truncatula cultivar Jemalong A17 lines, the Enodll::gus used in experiment 1, and SUNN, a super-nodulating mutant of A17, were germinated on orbit for 11 days in the middeck cabin and returned to Earth alive inside of BRIC-PDFU's at 4 C S. meliloti strains 1021 and ABS7 were cultivated separately in broth culture on orbit and also returned to Earth alive. After landing, flight- and ground-grown plants and bacteria were transferred from BRIC-PDFU's into Nunc(TradeMark) 4-well plates for reciprocity crosses. Rates of plant growth and nodule development on Buffered Nodulation Medium (lacking nitrogen) were measured for 14 days. Bacteria cultivated in microgravity in the

  12. [Initial experiences with propofol (Disoprivan) for anesthesia induction in pediatric anesthesia].

    Motsch, J; Must, W; Hutschenreuter, K


    Propofol is a new intravenous anesthetic agent that provides smooth and rapid induction of anesthesia. A short elimination half-life guarantees rapid recovery. Since it has been reformulated as an emulsion in soya bean oil, anaphylactoid reactions are unlikely to occur. As compared to adults, there is very little experience with propofol in pediatric anesthesia. The aim of this study was to evaluate propofol as an induction agent in children with respect to cardiovascular and respiratory effects and to investigate the incidence of other side-effects. METHOD. In 25 ASA I children aged 3-12 years (6.4 +/- 2.7 SD) anesthesia was induced with a single dose of propofol, after standard premedication with atropine 0.01 mg/kg and Thalamonal 0.04 ml/kg. Anesthesia was maintained with halothane, nitrous oxide, and oxygen. Blood pressure (BP), heart rate (HR), and arterial oxygen saturation (SaO2) were measured before and each minute for 6 min after propofol administration. The incidence of side-effects during induction of anesthesia as well as during recovery and the postoperative period were recorded. RESULTS. Propofol 2.5 mg/kg produced rapid and smooth induction of anesthesia. Mean arterial pressure decreased after 1 min by 14.3% with a maximum of 16.8% after 3 min. HR was influenced differently by propofol; children with initially high HR had a decrease in HR, whereas in children with a low initial rate, HR increased transiently. After 1 min, no further changes occurred. Although no apnea was observed, respiration was shallow and depressed, as indicated by a decrease in SaO2. Two children complained of pain and 4 of discomfort at the site of the injection; 1 of these developed transient phlebitis.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. The Workplace Experiences of Beginning Teachers in Three Countries: A Message for Initial Teacher Education from the Field

    du Plessis, Anna Elizabeth; Sunde, Eva


    Previous research indicates that beginning teachers are not fully prepared for what awaits them in the workforce. This study highlights the value of partnerships among higher education providers, schools and employers and links the experiences of beginning teachers to initial teacher education (ITE). Real-life experiences from the field provide…

  14. Post Traumatic Glioma – An association questioned

    Chaurasia I.D.


    Full Text Available Post traumatic glioma has been a matter of debate. Few reports favor its occurrence in previous head injury scar, subsequently developing into glioma. Here we report a case of young patient presented with headache, seizures and gradual loss of vision. On investigation found to have brain tumor. Patient had head injury occurred 3 yrs back. It fulfills all the criteria required to establish traumatic origin, further supporting the association.

  15. Targeted Radiolabeled Compounds in Glioma Therapy.

    Cordier, Dominik; Krolicki, Leszek; Morgenstern, Alfred; Merlo, Adrian


    Malignant gliomas of World Health Organization (WHO) grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiological features with survival times between more than 10 years (WHO II) and only several months (WHO IV). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of patients with glioma. The consistent overexpression of neurokinin type 1 receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labeled with different alpha-particle or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabeled substance P-based targeted glioma therapy compare favorably with standard therapy. Recently, labeling with the alpha particle emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08 mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical


    WANG Shu-chang; HUANG Si-xun; ZHANG Wei-min; ZHU Xiao-qian; CAO Xiao-qun; LI Yi


    Initialization and initial imbalance problem were discussed in the context of a three-dimensional variational data assimilation system of the new generation "Weather Research and Forecasting Model". Severaloptions of digital filter initialization have been tested with a rain storm case. It is shown that digital filter initialization, especially diabatic digital filter initialization and twice digital filter initialization, have effectively removed spurious high frequency noise from initial data for numerical weather prediction and produced balanced initial conditions. For six consecutive intermittent data assimilation cycles covering a 3-day period, mean initialization increments and impact on forecast variables are studied. DFI has been demonstrated to provide better adjustment of the hydrometeors and vertical velocity, reduced spin-up time, and improved forecast variables quantity.

  17. Balloon-augmented Onyx endovascular ligation: initial human experience and comparison with coil ligation.

    Osanai, Toshiya; Bain, Mark D; Toth, Gabor; Hussain, M Shazam; Hui, Ferdinand K


    Carotid artery sacrifice remains an important procedure for cerebral vascular disorders despite the development of new endovascular devices. Conventional carotid artery sacrifice with detachable coils alone often requires numerous coils to complete occlusion. To describe the initial human experience with balloon-augmented Onyx and coil vessel sacrifice based on our previous experience with animals. We performed a retrospective review of patients who underwent carotid artery sacrifice between 2008 and 2012 in accordance with local investigational review board approval. Two methods were used to occlude carotid arteries-namely, combined Onyx and coil embolization and traditional coil embolization. We compared the two methods for the cost of embolizate, time to occlude the vessels, and the number of coils. Eight consecutive patients (combined group n=3, traditional group n=5) were assessed. The median cost of embolic material was $6321 in the combined Onyx and coil embolization group and $29 996 in the traditional coil embolization group. The median time from first coil placement to achievement of vessel occlusion was 52 min in the Onyx group and 113 min in the coil embolization group. The median number of coils used was 4 in the Onyx group and 35 in the coil embolization group (p<0.05). No symptomatic complications or recurrences were seen in the combined group. Balloon-augmented Onyx endovascular ligation may reduce costs and fluoroscopy times during vessel sacrifice. Further studies in a larger number of patients are needed to confirm these findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  18. Initial Results from the STEM Student Experiences Aboard Ships (STEMSEAS) Program

    Lewis, J. C.; Cooper, S. K.; Thomson, K.; Rabin, B.; Alberts, J.


    The Science Technology Engineering and Math Student Experiences Aboard Ships (STEMSEAS) program was created as a response to NSF's call (through GEOPATHS) for improving undergraduate STEM education and enhancing diversity in the geosciences. It takes advantage of unused berths on UNOLS ships during transits between expeditions. During its 2016 pilot year - which consisted of three transits on three different research vessels in different parts of the country, each with a slightly different focus - the program has gained significant insights into how best to create and structure these opportunities and create impact on individual students. A call for applications resulted in nearly 900 applicants for 30 available spots. Of these applicants, 32% are from minority groups underrepresented in the geosciences (Black, Hispanic, or American Indian) and 20% attend community colleges. The program was able to sail socioeconomically diverse cohorts and include women, veterans, and students with disabilities and from two- and four-year colleges. Twenty-three are underrepresented minorities, 6 attend community colleges, 5 attend an HBCU or tribal college, and many are at HSIs or other MSIs. While longer term impact assessment will have to wait, initial results and 6-month tracking for the first cohort indicate that these kinds of relatively short but intense experiences can indeed achieve significant impacts on students' perception of the geosciences, in their understanding of STEM career opportunities, their desire to work in a geoscience lab setting, and to incorporate geosciences into non-STEM careers. Insights were also gained into the successful makeup of mentor/leader groups, factors to consider in student selection, necessary pre- and post-cruise logistics management, follow-up activities, structure of activities during daily life at sea, increasing student networks and access to mentorships, and leveraging of pre-existing resources and ship-based opportunities

  19. Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3 activation.

    Kiekow, Cíntia J; Figueiró, Fabrício; Dietrich, Fabrícia; Vechia, Luciana Dalla; Pires, Elisa N S; Jandrey, Elisa H F; Gnoatto, Simone C B; Salbego, Christianne G; Battastini, Ana Maria O; Gosmann, Grace


    Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low μM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-κB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Suppression of glioma progression by Egln3.

    Vicki A Sciorra

    Full Text Available Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3, a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

  1. Pancreas Preservation With Viaspan, Celsior, and Custodiol Solutions: An Initial Experience.

    Montiel-Casado, M C; Pérez-Daga, J A; Blanco-Elena, J A; Aranda-Narváez, J M; Sánchez-Pérez, B; Cabello-Díaz, M; Ruiz-Esteban, P; León-Díaz, F J; Gutiérrez-de la Fuente, C; Santoyo-Santoyo, J


    There is still controversy about which preservation solution in pancreas transplantation could be the best. The aim of this study was to analyze our initial experience with Custodiol solution (CuS) compared with Viaspan solution (VS) and Celsior solution (CS) in pancreas transplantation. A retrospective study included 94 consecutive pancreatic transplants, from 2007 until 2015. We compared 3 groups, depending on preservation solution: Viaspan (n = 41), Celsior (n = 40), or Custodiol (n = 13). The primary end point was patient and pancreas survival at 1 year after pancreas transplantation. The recipient and donor characteristics were similar except in cold ischemia time; it was higher with Celsior. No differences were found in postoperative complications and pancreas graft function at 3 months, 6 months, and 1 year (glucose, HbA1c, C-peptide, creatinine). The pancreas and patient survival at 1 year was comparable (pancreas survival: VS, 80%; CS, 90%; CuS, 92%; log-rank, 0.875; and patient survival: VS, 92%; CS, 97%; CuS, 100%; log-rank, 0.9). In our institution, the Custodiol solution in pancreas transplantation presented similar outcomes in terms of postoperative complications, pancreas graft function, and 1-year survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Implementing a robotics curriculum at an academic general surgery training program: our initial experience.

    Winder, Joshua S; Juza, Ryan M; Sasaki, Jennifer; Rogers, Ann M; Pauli, Eric M; Haluck, Randy S; Estes, Stephanie J; Lyn-Sue, Jerome R


    The robotic surgical platform is being utilized by a growing number of hospitals across the country, including academic medical centers. Training programs are tasked with teaching their residents how to utilize this technology. To this end, we have developed and implemented a robotic surgical curriculum, and share our initial experience here. Our curriculum was implemented for all General Surgical residents for the academic year 2014-2015. The curriculum consisted of online training, readings, bedside training, console simulation, participating in ten cases as bedside first assistant, and operating at the console. 20 surgical residents were included. Residents were provided the curriculum and notified the department upon completion. Bedside assistance and operative console training were completed in the operating room through a mix of biliary, foregut, and colorectal cases. During the fiscal years of 2014 and 2015, there were 164 and 263 robot-assisted surgeries performed within the General Surgery Department, respectively. All 20 residents completed the online and bedside instruction portions of the curriculum. Of the 20 residents trained, 13/20 (65 %) sat at the Surgeon console during at least one case. Utilizing this curriculum, we have trained and incorporated residents into robot-assisted cases in an efficient manner. A successful curriculum must be based on didactic learning, reading, bedside training, simulation, and training in the operating room. Each program must examine their caseload and resident class to ensure proper exposure to this platform.

  3. CT-guided spinal injection: initial experience with Sprotte tip needles

    Pua, Uei [Tan Tock Seng Hospital, Department of Diagnostic Radiology, Singapore (Singapore)


    The purpose of this paper is to describe our initial experience and to illustrate the potential benefits of using small caliber (25 and 27 G), noncutting pencil point needles (Sprotte) with single puncture coaxial technique in CT-guided spinal intervention (CTSI). From January 2009 to June 2009, Sprotte needles with single puncture coaxial technique were used in a total of ten patients for selective nerve root block (SNRB), facet joint block, and pars block under CT fluoroscopy (total of 16 target structures). All procedures were performed without conscious sedation, and visual analog scale (VAS) scores were recorded to determine pain related to needle placement. Total CT fluoroscopy time and out-of-plane needle deviation were obtained. Final needle position was documented by contrast injection for SNRBs and image capture for joint space cannulation. Sixteen out of the 16 structures were successfully targeted. No increase in VAS scores associated with needle placement was recorded, after infiltration of local anesthesia. Optimal peri-neurograms were obtained in all cases of SNRB, despite the side-hole opening in the Sprotte needles. Mean CT fluoroscopy time was 2 s (range 2-8 s per structure), and there was no case of out-of-plane needle deviation that required adjustment of the CT gantry. The use of small caliber Sprotte needles in CTSI is technically feasible and represents a potential refinement to current techniques in the management of chronic spinal pain. (orig.)

  4. A nonsurgical endodontics relational research database: the initial six years of experience.

    Iqbal, Mian K; Shukovsky, Deborah Gortler; Wong, Steven; Vohra, Gayatri


    The purpose of this study was to report results of the initial six years of experience utilizing a nonsurgical root canal treatment (NSRCT) database; to compare patient characteristics, operative procedures, and patient outcomes observed in the database to those observed in other studies; and to discuss the potential benefits of a clinical endodontic database. A total of 7,372 NSRCT cases performed by endodontic residents at the University of Pennsylvania from 2000 to 2006 were evaluated. The odds ratio (OR) for caries and trauma being causative agents for NSRCT in

  5. Contrast-enhanced ultrasound in ovarian tumors – diagnostic parameters: method presentation and initial experience



    The aim of this paper is to discuss and illustrate the use of contrast-enhanced ultrasound in evaluating ovarian tumors compared to conventional ultrasound, Doppler ultrasound and the histopathological analysis and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. We present the method and initial experience of our center by analyzing the parameters used in contrast-enhanced ultrasound in 6 patients with ovarian tumors of uncertain etiology. For examination we used a Siemens ultrasound machine with dedicated contrast software and the contrast agent SonoVue, Bracco. The patients underwent conventional ultrasound, Doppler ultrasound and i.v. administration of the contrast agent. The parameters studied were: inflow of contrast (rise time), time to peak enhancement, mean transit time. The series of patients is part of an extensive prospective PhD study aimed at elaborating a differential diagnosis protocol for benign versus malignant ovarian tumors, by validating specific parameters for contrast-enhanced ultrasound. Although the method is currently used with great success in gastroenterology, urology and senology, its validation in gynecology is still in the early phases. Taking into consideration that the method is minimally invasive and much less costly that CT/MRI imaging, demonstrating its utility in oncologic gynecology would be a big step in preoperative evaluation of these cases. PMID:26527912

  6. Robotic liver resection: initial experience with three-arm robotic and single-port robotic technique.

    Kandil, Emad; Noureldine, Salem I; Saggi, Bob; Buell, Joseph F


    Robotic-assisted surgery offers a solution to fundamental limitations of conventional laparoscopic surgery, and its use is gaining wide popularity. However, the application of this technology has yet to be established in hepatic surgery. A retrospective analysis of our prospectively collected liver surgery database was performed. Over a 6-month period, all consecutive patients who underwent robotic-assisted hepatic resection for a liver neoplasm were included. Demographics, operative time, and morbidity encountered were evaluated. A total of 7 robotic-assisted liver resections were performed, including 2 robotic-assisted single-port access liver resections with the da Vinci-Si Surgical System (Intuitive Surgical Sunnyvalle, Calif.) USA. The mean age was 44.6 years (range, 21-68 years); there were 5 male and 2 female patients. The mean operative time (± SD) was 61.4 ± 26.7 minutes; the mean operative console time (± SD) was 38.2 ± 23 minutes. No conversions were required. The mean blood loss was 100.7 mL (range, 10-200 mL). The mean hospital stay (± SD) was 2 ± 0.4 days. No postoperative morbidity related to the procedure or death was encountered. Our initial experience with robotic liver resection confirms that this technique is both feasible and safe. Robotic-assisted technology appears to improve the precision and ergonomics of single-access surgery while preserving the known benefits of laparoscopic surgery, including cosmesis, minimal morbidity, and faster recovery.

  7. Preparing beginning reading teachers: An experimental comparison of initial early literacy field experiences.

    Al Otaiba, Stephanie; Lake, Vickie E; Greulich, Luana; Folsom, Jessica S; Guidry, Lisa


    This randomized-control trial examined the learning of preservice teachers taking an initial Early Literacy course in an early childhood education program and of the kindergarten or first grade students they tutored in their field experience. Preservice teachers were randomly assigned to one of two tutoring programs: Book Buddies and Tutor Assisted Intensive Learning Strategies (TAILS), which provided identical meaning-focused instruction (shared book reading), but differed in the presentation of code-focused skills. TAILS used explicit, scripted lessons, and the Book Buddies required that code-focused instruction take place during shared book reading. Our research goal was to understand which tutoring program would be most effective in improving knowledge about reading, lead to broad and deep language and preparedness of the novice preservice teachers, and yield the most successful student reading outcomes. Findings indicate that all pre-service teachers demonstrated similar gains in knowledge, but preservice teachers in the TAILS program demonstrated broader and deeper application of knowledge and higher self-ratings of preparedness to teach reading. Students in both conditions made similar comprehension gains, but students tutored with TAILS showed significantly stronger decoding gains.

  8. Single-port laparoscopic approach of the left liver: initial experience.

    Camps Lasa, Judith; Cugat Andorrà, Esteban; Herrero Fonollosa, Eric; García Domingo, María Isabel; Sánchez Martínez, Raquel; Vargas Pierola, Harold; Rodríguez Campos, Aurora


    New technological advances have enabled the development of single-port laparoscopic surgery. This approach began with cholecystectomy and subsequently with other abdominal surgeries. However, few publications on laparoscopic liver surgery have described the use of complete single-port access. We present our initial experience of a single-port laparoscopic hepatectomy. Between May 2012 and December 2013, 5 single-port laparoscopic hepatectomies were performed: one for benign disease and four for colorectal liver metastases. The lesions were approached through a 3-5 cm right supraumbilical incision using a single-port access device. All the lesions were located in hepatic segments II or III. Four left lateral sectorectomies and one left hepatectomy were performed. Median operative time was 135 min. No cases were converted to conventional laparoscopic or open surgery. The oral intake began at 18 h. There were no postoperative complications and no patients required blood transfusion. The median hospital stay was 3 days. The degree of satisfaction was very good in 4 cases and good in one. Patients resumed their normal daily activities at 8 days. Single-port laparoscopic hepatectomy is safe and feasible in selected cases and may reduce surgical aggression and offer better cosmetic results. Comparative studies are needed to determine the real advantages of this approach. Copyright © 2014 AEC. Published by Elsevier Espana. All rights reserved.

  9. An initial experience with a digital drainage system during the postoperative period of pediatric thoracic surgery

    Costa, Altair da Silva; Bachichi, Thiago; Holanda, Caio; Rizzo, Luiz Augusto Lucas Martins De


    ABSTRACT Objective: To report an initial experience with a digital drainage system during the postoperative period of pediatric thoracic surgery. Methods: This was a prospective observational study involving consecutive patients, ≤ 14 years of age, treated at a pediatric thoracic surgery outpatient clinic, for whom pulmonary resection (lobectomy or segmentectomy via muscle-sparing thoracotomy) was indicated. The parameters evaluated were air leak (as quantified with the digital system), biosafety, duration of drainage, length of hospital stay, and complications. The digital system was used in 11 children (mean age, 5.9 ± 3.3 years). The mean length of hospital stay was 4.9 ± 2.6 days, the mean duration of drainage was 2.5 ± 0.7 days, and the mean drainage volume was 270.4 ± 166.7 mL. The mean maximum air leak flow was 92.78 ± 95.83 mL/min (range, 18-338 mL/min). Two patients developed postoperative complications (atelectasis and pneumonia, respectively). The use of this digital system facilitated the decision-making process during the postoperative period, reducing the risk of errors in the interpretation and management of air leaks. PMID:28117476

  10. Initial clinical experience using the Echo Navigator~-system during structural heart disease interventions

    Jan; Balzer; Tobias; Zeus; Katharina; Hellhammer; Verena; Veulemans; Silke; Eschenhagen; Eva; Kehmeier; Christian; Meyer; Tienush; Rassaf; Malte; Kelm


    AIM: To present our initial clinical experience using this innovative software solution for guidance of percutaneous structural heart disease interventions.METHODS: Left atrial appendage, atrial septal defect and paravalvular leak closure, transaortic valve repair and Mitra Clip procedures were performed in the catheter laboratory under fluoroscopic and echocardiographic guidance. The two-dimensional and three-dimensional images generated by the transesophageal echocardiography probe were interfaced with the fluoroscopic images in real-time using the Echo Navigator-system.RESULTS:The application of the novel image fusion technology was safe and led to a better appreciation of multimodality imaging guidance due to improved visualization of the complex relationship between catheter devices and anatomical structures.CONCLUSION:The Echo Navigator-system is a feasible and safe tool for guidance of interventional procedures in structural heart disease.This innovative technology may improve confidence of interventional cardiologists in targeting and positioning interventional devices in order to increase safety,accuracy,and efficacy of percutaneous interventions in the catheter laboratory.

  11. Initial experience with personal digital assistant-based reflectance photoplethysmograph for free tissue transfer monitoring.

    Stack, Brendan C; Futran, Neal D; Zang, Billy; Scharf, John E


    Improved microsurgical technique has resulted in a high percentage of successful free tissue transfers. When a tissue transfer fails in the head and neck, however, the results are orocutaneous fistulas, carotid artery exposure, and deformity that adds morbidity, expense, and may delay adjuvant therapy. Postoperative monitoring of tissue perfusion can detect early problems in free tissue transfer that may allow for early intervention and salvage. The authors have demonstrated that reflectance photoplethysmography can detect perfusion changes in free tissue transfer within 5 minutes of a pedicle "insult" intraoperatively. Normative data for viable flaps from various donor sites have been established. The authors now report their initial experience with a newly developed reflectance photoplethysmograph based on a hand-held computer for routine clinical use. Their results are compared with a conventional surveillance protocol that included observation, bleeding to pin prick, and bedside duplex scanning of the vascular pedicle. In a series of 30 free tissue transfers (29 patients), there was one ischemic event (skin paddle loss only), which was detected by the monitor. The monitor was able to predict correctly (one flap) survival of a free tissue transfer even when duplex ultrasonic data were indicative of an absence of perfusion. Personal digital assistant-based photoplethysmography appears to be a promising device for bedside diagnosis of free tissue transfer viability or ischemia.

  12. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Fine Howard A


    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  13. Microglia-glioma cross-talk: a two way approach to new strategies against glioma.

    Arcuri, Cataldo; Fioretti, Bernard; Bianchi, Roberta; Mecca, Carmen; Tubaro, Claudia; Beccari, Tommaso; Franciolini, Fabio; Giambanco, Ileana; Donato, Rosario


    Glioblastoma (GBM) is the most malignant and aggressive among primary brain tumors, characterized by very low life expectancy. In vivo, glioma and glioblastoma in particular contain large numbers of immune cells (myeloid cells) such as microglia and tumour-infiltrating macrophages (or glioma associated macrophages). These glioma-infiltrating myeloid cells comprise up to 30% of total tumor mass and have been suggested to play several roles in glioma progression including proliferation, survival, motility and immunosuppression. Although tumor microglia and macrophages can acquire proinflammatory (M1) phenotype being capable of releasing proinflammatory cytokines, phagocytosing and presenting antigens, their effector immune function in gliomas appears to be suppressed by the acquisition of an anti-inflammatory (M2) phenotype. In the present work we review the microglia-glioma interactions to highlight the close relationship between the two cell types and the factors that can influence their properties (chemokines, cytokines, S100B protein). A future therapeutic possibility might be to simultaneously targeting, for example with nanomedicine, glioma cells and microglia to push the microglia towards an antitumor phenotype (M1) and/or prevent glioma cells from "conditioning" by microglia.

  14. Known glioma risk loci are associated with glioma with a family history of brain tumours

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika


    Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive...

  15. Rising from failure and learning from success: The role of past experience in radical initiative taking

    D. Deichmann (Dirk); J.C.M. van den Ende (Jan)


    markdownabstract__Abstract__ We investigate how the successes and failures of people who initiate radical ideas influence (a) the inclination to take new personal initiatives and (b) the outcome of those initiatives. Using the data of 1,792 radical ideas suggested by 908 employees in a multinationa

  16. 78 FR 73518 - Notice Inviting Suggestions for New Experiments for the Experimental Sites Initiative; Federal...


    ... based experiments designed to test alternative ways of administering the student financial assistance... the suggestions submitted in response to this notice the Secretary will design experiments and... the Congress. ] We are particularly interested in experiments that are designed to improve...

  17. Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma-Tailored Gene Panel.

    Zacher, Angela; Kaulich, Kerstin; Stepanow, Stefanie; Wolter, Marietta; Köhrer, Karl; Felsberg, Jörg; Malzkorn, Bastian; Reifenberger, Guido


    Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) for the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types. Sensitivity and specificity of glioma gene panel NGS for detection of DNA sequence variants and copy number changes were validated by single gene analyses. NGS-based mutation detection was optimized for application on formalin-fixed paraffin-embedded tissue specimens including small stereotactic biopsy samples. NGS data obtained in a retrospective analysis of 121 gliomas allowed for their molecular classification into distinct biological groups, including (i) isocitrate dehydrogenase gene (IDH) 1 or 2 mutant astrocytic gliomas with frequent α-thalassemia/mental retardation syndrome X-linked (ATRX) and tumor protein p53 (TP53) gene mutations, (ii) IDH mutant oligodendroglial tumors with 1p/19q codeletion, telomerase reverse transcriptase (TERT) promoter mutation and frequent Drosophila homolog of capicua (CIC) gene mutation, as well as (iii) IDH wildtype glioblastomas with frequent TERT promoter mutation, phosphatase and tensin homolog (PTEN) mutation and/or epidermal growth factor receptor (EGFR) amplification. Oligoastrocytic gliomas were genetically assigned to either of these groups. Our findings implicate gene panel NGS as a promising diagnostic technique that may facilitate integrated histological and molecular glioma classification.

  18. Clinical and MRI features of supratentorial gliomas with adult-onset epilepsy

    Hashimoto, Takahiro; Yamaura, Akira (Chiba Univ. (Japan). School of Medicine); Watanabe, Osamu


    Although some patients with supratentorial gliomas develop epilepsy in their clinical course, the details of adult-onset epilepsy with gliomas have not been fully evaluated. This paper reports on 15 cases of supratentorial glioma with the sole symptom of adult-onset epilepsy and characterizes their clinical and MRI features. The patients, 5 males and 10 females, developed the first epilepsy at the mean age of 37 years. Generalized seizure was encountered in all cases and focal seizure alone was never seen. Seizure was satisfactorily controlled with anticonvulsants in all except 2 cases. The tumor was located in the frontal lobe (9 cases) or temporal lobe (6 cases). Histologically, there were 12 astrocytomas, 2 glioblastomas, and 1 oligoastrocytoma. Of these, 12 were benign gliomas. Surprisingly, CT scan and MRI revealed tumors larger than predicted. The abnormal intensity region was delineated most prominently on T[sub 2]-weighted SE image and was broader on T[sub 2]-weighted spin echo image than on T[sub 1]-weighted spin echo and inversion recovery image. The authors conclude that gliomas presenting with epilepsy tend to be histologically benign, are predominantly seen in middle-aged women, and are located in the frontal and temporal lobes. Although a tumor may be large enough to be detected on CT scan or MRI, as in the present study, histological examination is needed to establish the diagnosis. Additionally, gliomas with equivocal abnormalities on CT and MRI do evolve despite further neurological deficits, so meticulous evaluation including stereotactic biopsy is the method of choice. Finally, T[sub 2]-weighted SE image in the coronal plane is advocated for patients with adult-onset epilepsy to achieve accurate diagnosis and to initiate early treatment. (author).

  19. Challenges conducting comparative effectiveness research: the Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE experience

    Friedly JL


    Full Text Available Janna L Friedly,1,4 Zoya Bauer,2,4 Bryan A Comstock,3,4 Emily DiMango,5 Assiamira Ferrara,6 Susan S Huang,7 Elliot Israel,8 Jeffrey G Jarvik,2,4 Andrew A Nierenberg,9 Michael K Ong,10 David F Penson,11 Rebecca Smith-Bindman,12 Arthur E Stillman,13 William M Vollmer,6 Stephen M Warren,14 Chunliu Zhan,15 David Chu-Wen Hsia,15 Anne Trontell15 1Department of Rehabilitation Medicine, 2Department of Radiology, 3Department of Biostatistics, 4Comparative Effectiveness, Cost and Outcomes Research Center, University of Washington, Seattle, WA, 5Columbia University Medical Center, New York, NY, 6Kaiser Foundation Research Institute, Oakland, 7Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine School of Medicine, Irvine, CA, 8Harvard Medical School, Pulmonary and Critical Care, Allergy and Immunology, Brigham and Women's Hospital, 9Massachusetts General Hospital, Boston, MA, 10Division of General Internal Medicine & Health Services Research, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 11Vanderbilt University and Tennessee Valley VAHCC, Nashville, TN, 12Departments of Radiology and Biomedical Imaging, Health Policy, Epidemiology and Biostatistics, University of California, San Francisco, SF, 13Emory University, Atlanta, GA, 14Department of Plastic Surgery, Division of Clinical and Translational Research, NYU Langone Medical Center, New York, NY, 15Agency for Healthcare Research and Quality, Rockville, MD, USA Abstract: The Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE program, which includes 12 ongoing comparative effectiveness research (CER trials funded by the Agency for Healthcare Research and Quality under the American Recovery and Reinvestment Act of 2009, has had firsthand experience in dealing with the unique challenges of conducting CER since the trials started in the fall of 2010. This paper will explore the collective experience

  20. Initial experience of occluding special type patent ductus arterioses using the Amplatzer vascular plug

    ZHANG Po; ZHU Xian-yang; WANG Qi-guang; ZHANG Duan-zhen; HAN Xiu-min


    Background Occluders licensed for clinical use are not fit for some special Krichenko E patent ductus arterioses.The Amplatzer vascular plug I (AVP1) has not been licensed for use for closure of patent ductus arteriose.We report our initial experience to occluding special type patent ductus arterioses with the AVP1-a single lobe device of single layer Nitinol mesh for short vessel landing zones.Methods Patients referred with small and long Krichenko E patent ductus arterioses 1 mm to 3 mm in diameter underwent occlusion using AVP1.All cases underwent pre-,intra-and post-procedural echocardiography and chest X-ray at the completion of the procedure,the next day and at a 30-day,3-month and 6-month follow-up visits.Device sizing for device waist diameter and length was based on aortography.Results From April 2008 to June 2012,26 patients with a mean age of (7.6±8.0) years (range 6 months-32 years)and a mean weight of (23.8±14.8) kg (range 7-67 kg) underwent successful patent ductus arteriose closure.The mean ductus diameter was (2.1±0.7) mm (range 1-3 mm).Transpulmonary (22/26) and transaortic approaches (4/26) were used.No persistent patency was observed after 24 hours and after one month.No device displacement,residual flow and iatrogenic coarctation of the aorta were observed after three months and six months.Conclusions The AVP1 makes it easy to close some Krichenko E patent ductus arterioses.Smaller delivery catheter profile and symmetric cylindrical device shape allow for use for small and long Krichenko E patent ductus arterioses 1 mm to 3 mm in diameter and small patients through transaortic approaches.Broader experience is required to further delineate device and patient selection as well as to document its long-term efficacy and safety.

  1. Social and Psychological Predictors of Initial Cigarette Smoking Experience: A Survey in Male College Students.

    Menati, Walieh; Nazarzadeh, Milad; Bidel, Zeinab; Würtz, Morten; Menati, Rostam; Hemati, Rohollah; Yaghoubi, Maryam; Zareimanesh, Elham; Mohammadi, Mohammad Sabour; Akhlaghi Ardekani, Farzad; Tazval, Jafar; Delpisheh, Ali


    Knowledge about social and psychological risk factors for initial cigarette smoking experience (ICSE) is sparse. The present study aimed to estimate the prevalence of ICSE and to examine the psychological and social factors related to ICSE. In a cross-sectional survey, 1,511 male college students were recruited using multistage sampling techniques from four universities located within the city of Ilam, Iran. Self-administered multiple-choice questionnaires were distributed to students from March to June 2013. Risk factors for ICSE were evaluated using logistic regression models. Participants were 22.3 ± 2.4 years of age. ICSE prevalence was 30.6%. In multivariable adjusted analysis, risk taking behavior (odds ratio [OR] = 1.61; 95% confidence interval [CI] = 1.11-2.33), perceived peer smoking prevalence (OR = 2.48; 95% CI = 1.03-5.97), positive thoughts about smoking (OR = 1.06; 95% CI = 1.02-1.10), high self-efficacy (OR = 0.95, 95% CI [0.93, 0.98]), presence in smokers' gathering (OR = 4.45; 95% CI = 2.88-6.81), comity of smokers (OR = 2.56; 95% CI = 1.66, 3.92), very hard access to cigarettes (OR = 2.20; 95% CI = 1.16-4.16), close friends' medium reaction toward smoking (OR = 1.38; 95% CI = 1.02-1.88), and sporting activity (OR = 0.74; 95% CI = 0.56-0.98) were significantly associated with ICSE. This study identified that a combination of psychological and social variables account for up to 78% of the probability of ICSE. The most important protective factor against ICSE was physical activity, whereas the most important risk factor for ICSE was frequent gathering in the presence of smokers.

  2. SU-E-J-181: Magnetic Resonance Image-Guided Radiation Therapy Workflow: Initial Clinical Experience

    Green, O; Kashani, R; Santanam, L; Wooten, H; Li, H; Rodriguez, V; Hu, Y; Mutic, S [Washington University School of Medicine, St. Louis, MO (United States); Hand, T; Victoria, J [ViewRay, Inc., Oakwood Village, OH (United States); Steele, C [Barnes Jewish Hospital, St Louis, MO (United States)


    Purpose: The aims of this work are to describe the workflow and initial clinical experience treating patients with an MRI-guided radiotherapy (MRIGRT) system. Methods: Patient treatments with a novel MR-IGRT system started at our institution in mid-January. The system consists of an on-board 0.35-T MRI, with IMRT-capable delivery via doubly-focused MLCs on three {sup 60} Co heads. In addition to volumetric MR-imaging, real-time planar imaging is performed during treatment. So far, eleven patients started treatment (six finished), ranging from bladder to lung SBRT. While the system is capable of online adaptive radiotherapy and gating, a conventional workflow was used to start, consisting of volumetric imaging for patient setup using visible tumor, evaluation of tumor motion outside of PTV on cine images, and real-time imaging. Workflow times were collected and evaluated to increase efficiency and evaluate feasibility of adding the adaptive and gating features while maintaining a reasonable patient throughput. Results: For the first month, physicians attended every fraction to provide guidance on identifying the tumor and an acceptable level of positioning and anatomical deviation. Average total treatment times (including setup) were reduced from 55 to 45 min after physician presence was no longer required and the therapists had learned to align patients based on soft-tissue imaging. Presently, the source strengths were at half maximum (7.7K Ci each), therefore beam-on times will be reduced after source replacement. Current patient load is 10 per day, with increase to 25 anticipated in the near future. Conclusion: On-board, real-time MRI-guided RT has been incorporated into clinical use. Treatment times were kept to reasonable lengths while including volumetric imaging, previews of tumor movement, and physician evaluation. Workflow and timing is being continuously evaluated to increase efficiency. In near future, adaptive and gating capabilities of the system will

  3. MRI-guided percutaneous laser ablation of small renal cell carcinoma: Initial clinical experience

    Kariniemi, Juho; Ojala, Risto; Hellstroem, Pekka; Sequeiros, Roberto Blanco (Dept. of Radiology, Dept. of Surgery, Oulu Univ. Hospital, Oulu (Finland)), e-mail:


    Background: The number of detected small renal cell carcinomas (RCCs) has been rising, largely due to advances in imaging. Open surgical resection is the standard management of small RCCs; however, imaging-guided percutaneous ablative therapies have emerged as a minimally invasive treatment alternative, especially for patients who are poor candidates for surgery. Purpose: To evaluate the initial clinical experience of magnetic resonance imaging (MRI)-guided percutaneous laser ablation of small RCCs. Material and Methods: Eight patients with 10 tumors were treated with percutaneous MRI-guided laser ablation. All tumors (diameter range 1.5-3.8 cm, mean 2.7 cm) were biopsy-proven RCCs. By using a 0.23 T open MRI system and general anesthesia in patients, one to four (mean 2.6) laser fibers were placed and the tumors were ablated under near real-time MRI control by observing the signal void caused by the temperature change in the heated tissue. The treatment was considered successful if the tumor showed no contrast enhancement at follow-up imaging. Results: All except one tumor were successfully ablated in one session. The first patient treated showed enhancing residual tumor in post-procedural MRI; she has thus far declined retreatment. One complication, a myocardial infarction, occurred; all other patients tolerated the procedure well. No local recurrence was discovered during the follow-up (range 12-30 months, mean 20 months). Conclusion: In this small group of patients with relatively short follow-up period, MRI-guided percutaneous laser ablation proved to be a promising treatment option for small RCCs

  4. Initial experience of percutaneous treatment of mitral regurgitation with MitraClip® therapy in Spain.

    Carrasco-Chinchilla, Fernando; Arzamendi, Dabit; Romero, Miguel; Gimeno de Carlos, Federico; Alonso-Briales, Juan Horacio; Li, Chi-Hion; Mesa, Maria Dolores; Arnold, Roman; Serrador Frutos, Ana María; Pan, Manuel; Roig, Eulalia; Rodríguez-Bailón, Isabel; de la Fuente Galán, Luis; Hernández, José María; Serra, Antonio; Suárez de Lezo, José


    Symptomatic mitral regurgitation has an unfavorable prognosis unless treated by surgery. However, the European registry of valvular heart disease reports that 49% of patients with this condition do not undergo surgery. Percutaneous treatment of mitral regurgitation with MitraClip® has been proved a safe, efficient adjunct to medical treatment in patients with this profile. The objective of the present study is to describe initial experience of MitraClip® therapy in Spain. Retrospective observational study including all patients treated between November 2011 and July 2013 at the 4 Spanish hospitals recording the highest numbers of implantations. A total of 62 patients (77.4% men) were treated, mainly for restrictive functional mitral regurgitation (85.4%) of grade III (37%) or grade IV (63%), mean (standard deviation) ejection fraction 36% (14%), and New York Heart Association functional class III (37%) or IV (63%). Device implantation was successful in 98% of the patients. At 1 year, 81.2% had mitral regurgitation ≤ 2 and 90.9% were in New York Heart Association functional class ≤ II. One periprocedural death occurred (sepsis at 20 days post-implantation) and another 3 patients died during follow-up (mean, 9.1 months). Two patients needed a second implantation due to partial dehiscence of the first device and 2 others underwent heart transplantation. In Spain, MitraClip® therapy has principally been aimed at patients with functional mitral regurgitation, significant systolic ventricular dysfunction, and high surgical risk. It is considered a safe alternative treatment, which can reduce mitral regurgitation and improve functional capacity. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  5. Transperineal prostate biopsy with ECHO-MRI fusion. Biopsee system. Initial experience.

    Romero-Selas, E; Cuadros, V; Montáns, J; Sánchez, E; López-Alcorocho, J M; Gómez-Sancha, F


    The aim of this study is to present our initial experience with the stereotactic echo-MRI fusion system for diagnosing prostate cancer. Between September 2014 and January 2015, we performed 50 prostate biopsies using the stereotactic echo-MRI fusion system. The 3-Tesla multiparameter MR images were superimposed using this image fusion system on 3D echo images obtained with the Biopsee system for the exact locating of areas suspected of prostate cancer. The lesions were classified using the Prostate Imaging Report and Date System. We assessed a total of 50 patients, with a mean age of 63 years (range, 45-79), a mean prostate-specific antigen level of 8 ng/mL (range, 1.9-20) and a mean prostate volume of 52mL (range, 12-118). Prostate cancer was diagnosed in 69% of the patients and intraepithelial neoplasia in 6%. The results of the biopsy were negative for 24% of the patients. The results of the biopsy and MRI were in agreement for 62% of the patients; however, 46% also had a tumour outside of the suspicious lesion. We diagnosed 46% anterior tumours and 33% apical tumours. One patient had a haematuria, another had a haematoma and a third had acute urine retention. Multiparametric prostatic MRI helps identify prostate lesions suggestive of cancer. The Biopsee echo-MRI fusion system provides for guided biopsy and increases the diagnostic performance, reducing the false negatives of classical biopsies and increasing the diagnosis of anterior tumours. Transperineal access minimises the risk of prostatic infection and sepsis. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Initial Australian experience with high dose indium-111 pentreotide therapy in progressive, symptomatic neuroendocrine tumours

    Hicks, R.J.; Keady, M.A.; Johnson, V. [The Peter McCallum Cancer Institute, Melbourne, VIC (Australia). Department of Nuclear Medicine and PET


    Full text: Neuroendocrine tumours variably express somatostatin receptors enabling imaging using somatostatin analogues, including In-111 pentreotide. Due to the emission of Auger electrons in the decay of In-1 11, there is the potential to use this agent for therapy. Based on favourable experience with high dose In-111 pentreotide therapy a the University of Rotterdam, a prospective trial of this treatment was performed in 6 patients with progressive, symptomatic neuroendocrine tumours (carcinoid in 4 patients and glucagonoma in 2 patients). Patients were selected based on the presence of uptake at multiple sites on In-1 11 pentreotide scanning with intensity equal to or greater than splenic activity. Follow-up of haematology, endocrine and renal function was performed and serial imaging correlation of index lesions was performed. Three treatments of approximately 6.5 GBq of In-111 pentreotide were administered to each patient over 3-5 months. One pt with bone metastases from carcinoid had an initial flare in symptoms 1 week following treatment but subsequent palliation which lasted 6 months before requiring local radiotherapy. The three remaining carcinoid patients had symptomatic improvement and reduced 5-HIAA levels when abnormal at baseline. Both patients with glucagonoma had symptomatic improvement and reduction in glucagon levels. No patients had evidence of disease progression up to 6 months post-treatment in index lesions with high In-1 11 pentreotide uptake. One lesion with low uptake progressed despite regression in other lesions with high uptake in the same patient Minor transient lymphopaenia was seen following treatment but no clinically significant toxicity was noted. These preliminary results complement European data suggesting good palliation from high dose In-111 pentreotide therapy in patients with high somatostatin receptor expression

  7. Initial experience in Brazil with the Helex septal occluder for percutaneous occlusion of atrial septal defects

    Pedra Carlos A.C.


    Full Text Available OBJECTIVE: To evaluate the initial clinical experience with the Helex septal occluder for percutaneous closure of atrial septal defects. METHODS: Ten patients underwent the procedure, 7 patients with ostium secundum atrial septal defects (ASD with hemodynamic repercussions and 3 patients with pervious foramen ovale (PFO and a history of stroke. Mean age was 33.8 years and mean weight was 55.4 kg. Mean diameter by transesophageal echocardiography and mean stretched ASD diameter were 11.33 ± 3.3mm, and 15.2 ± 3.8mm, respectively. The Qp/Qs ratio was 1.9 ± 0.3 in patients with ASD. RESULTS: Eleven occluders were placed because a patient with 2 holes needed 2 devices. It was necessary to retrieve and replace 4 devices in 3 patients. We observed immediate residual shunt (< 2mm in 4 patients with ASD, and in those with patent foramen ovale total occlusion of the defect occurred. No complications were noted, and all patients were discharged on the following day. After 1 month, 2 patients with ASD experienced trivial residual shunts (1mm. In 1 patient, we observed mild prolapse in the proximal disk in the right atrium, without consequences. CONCLUSION: The Helex septal occluder was safe and effective for occluding small to moderate atrial septal defects. Because the implantation technique is demanding, it requires specific training of the operator. Even so, small technical failures may occur in the beginning of the learning curve, but they do not involve patient safety.

  8. Initial experience with the Codman Certas adjustable valve in the management of patients with hydrocephalus

    Watt Sara


    Full Text Available Abstract Background A new adjustable valve, the Codman CertasTM valve for treatment of hydrocephalus was introduced into clinical practice in January 2011. It has 8 different settings with an opening pressure varying from 36 to over 400 mm H2O at a flow rate of 20 mL/h. The 8th setting is designed to provide a "virtual off" function. The objective of this report is to describe the initial clinical experience with the CertasTM valve and evaluate clinical usage with the main focus on the portable adjustment device - Therapeutic Management System (TMS, the “virtual off” setting and compatibility with magnetic resonance imaging (MRI. Findings Forty-two patients with hydrocephalus from different etiologies were treated with the CertasTM adjustable shunt system. Data regarding implantation procedures, the use of the TMS system, x-ray imaging, and MRI procedures were recorded prospectively. All patients had clinical follow-up at four weeks after implantation and every three months until a stable clinical condition was obtained. The mean time for follow-up was 8.6 months (1–16.6. Seventy-one adjustments were performed with the TMS, 12 were problematic. Twenty-nine MRI procedures were performed and did not cause accidental resetting. Five patients were treated with the "virtual off" function for a period. Conclusions We found the CertasTM valve valuable in the treatment of hydrocephalus, usability of the TMS was high because it is small and portable, but in some cases we experienced adjustment problems with the first procedures performed by a surgeon, indicating that there is a learning curve. The "virtual off" function provided a possibility of treating over-drainage without the need for shunt ligation or other invasive procedures.

  9. Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience.

    Ntourakis, Dimitrios; Memeo, Ricardo; Soler, Luc; Marescaux, Jacques; Mutter, Didier; Pessaux, Patrick


    Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.

  10. Single-incision laparoscopic colectomy without using special articulating instruments: an initial experience

    Trakarnsanga Atthaphorn


    Full Text Available Abstract Background Single-incision laparoscopic colectomy (SILC was introduced as a novel minimally invasive technique. The benefits of this technique include reducing number of the incision and cosmetic improvement. Unlike the conventional laparoscopic colectomy, majority of previously reported SILC need to be performed using special curved or articulated instruments. The purpose of this study is to demonstrate our initial experience of SILC, which could be performed using the standard laparoscopic instruments. Material and methods Retrospective review of 14 patients who underwent SILC at Siriraj Hospital from May to December 2010, patient's demographic data, perioperative outcomes, early postoperative complications and pathological data were collected and analyzed. Results The mean age of all patients was 60 years. The most common operation with SILC was sigmoidectomy (n = 9, followed by right hemicolectomy (n = 2, left hemicolectomy (n = 1, anterior resection (n = 1, and total colectomy (n = 1. The trocar insertion techniques were multi-fascial incision using regular port (n = 11 and GelPOINT® (n = 3. The mean operative time was 155 minutes (range 90-280 and the mean estimate blood loss was 32.1 mL (range 10-100. All patients were successfully operated without conversion. The mean length of hospital stay was 9 days (range 5-20. There was no mortality. The pathological results revealed colorectal cancer (n = 12, neoplastic polyp (n = 1 and Familial adenomatous polyposis (FAP (n = 1. The mean number of lymph nodes retrieval was 16.6 (range 3-34. Conclusion SILC can successfully and safely be performed with standard laparoscopic instruments. This technique might be an alternative procedure to conventional laparoscopic colectomy with better cosmetic result.

  11. Initial experience with extreme angle cervical screw for treatment of trauma and cervical spondylosis.

    Mehta, Ankit I; Babu, Ranjith; Bagley, Carlos A; Grossi, Peter M; Gottfried, Oren N


    In this study, we have described our initial experience and surgical technique of extreme angle screw placement in the cervical and upper thoracic spine of a cohort of patients undergoing posterior fusion. This extreme angle screw facilitates rod placement without need for any coronal contouring of the rod or offset connectors despite the varied entry site locations for posterior instrumentation and the different trajectories and pathways of these screws. From ruary 2011 to July 2011, extreme angle screws were placed in twenty consecutive adult patients who underwent posterior cervical, occipital-cervical or cervical-thoracic fusions. The primary diagnosis was cervical spondylotic myelopathy (13), trauma (4), and pseudoarthrosis with stenosis (3). Eight patients had gross instability. A total of 196 screws were placed; half of the cases involved instrumentation at or within the C3-7 segments (10) and the others included constructs extending to occipital bone, C2, T1, or T2 (10). Of all twenty cases, there were no perioperative hardware complications. At long-term follow-up, two patients required reoperation, one for hardware failure and the other for single level symptomatic pseudoarthrosis. We conclude that extreme angle screw use in the posterior cervical spine provides an evolution in posterior instrumentation that maximizes the biomechanical strength of a construct, allows for easy rod placement, and may improve the restoration of sagittal alignment. Overall, extreme angle screws facilitate rod placement even for screws offset from the natural plane of the rod, thereby avoiding the need for coronal contouring or placement of offset connectors.

  12. Pneumatic reduction of intussusception in children at Korle Bu Teaching Hospital: An initial experience

    Yaw Boateng Mensah


    Full Text Available Background: Intussusception is a common abdominal emergency in children which necessitates prompt diagnosis and management. Nonsurgical methods of managing this condition are rapidly gaining popularity with fluoroscopic-guided pneumatic reduction being one of such methods that has been used with great success in many countries. We present our initial experience with fluoroscopic-guided pneumatic reduction of intussusception at Korle Bu Teaching Hospital which is also the first time the technique has been used in Ghana. Materials and Methods: A total of 18 children were enrolled in the study between August 2007 and February 2008 at Korle Bu Teaching Hospital, Accra, Ghana. Patients were given air enema under fluoroscopic-guidance using locally assembled equipment. The intraluminal pressure was monitored with a pressure gauge and was not permitted to go above 120 mmHg. A total of three attempts of 3 min each were allowed. Results: There were 12 males and 6 females. The average age of the patients was 8.3 months (SD= 3 months. Twelve (67% of the cases were reduced successfully while 6 (33% failed to reduce. A majority of those that did not reduced had symptoms for at least 2 days. Bowel perforation occurred in three (16.7% cases. Conclusion: Pneumatic reduction of intussusception is a cost-effective and rapid method of management of intussusception. It however has limitations like high reported rate of bowel perforation and limited ability to identify lead points. The benefits however seem to outweigh these challenges, such as fluoroscopic-guided pneumatic reduction has a very high success rate. Fluoroscopic guided pneumatic reduction should be considered as one of the primary modes of reduction in Ghana and other neighbouring countries that are yet to practice it.

  13. Robotic-assisted laparoscopic partial nephrectomy: initial experience in Brazil and a review of the literature

    Carlo Camargo Passerotti


    Full Text Available CONTEXT AND PURPOSE: Partial nephrectomy has become the standard of care for renal tumors less than 4 cm in diameter. Controversy still exists, however, regarding the best surgical approach, especially when minimally invasive techniques are taken into account. Robotic-assisted laparoscopic partial nephrectomy (RALPN has emerged as a promising technique that helps surgeons achieve the standards of open partial nephrectomy care while offering a minimally invasive approach. The objective of the present study was to describe our initial experience with robotic-assisted laparoscopic partial nephrectomy and extensively review the pertinent literature. MATERIALS AND METHODS: Between August 2009 and February 2010, eight consecutive selected patients with contrast enhancing renal masses observed by CT were submitted to RALPN in a private institution. In addition, we collected information on the patients' demographics, preoperative tumor characteristics and detailed operative, postoperative and pathological data. In addition, a PubMed search was performed to provide an extensive review of the robotic-assisted laparoscopic partial nephrectomy literature. RESULTS: Seven patients had RALPN on the left or right sides with no intraoperative complications. One patient was electively converted to a robotic-assisted radical nephrectomy. The operative time ranged from 120 to 300 min, estimated blood loss (EBL ranged from 75 to 400 mL and, in five cases, the warm ischemia time (WIT ranged from 18 to 32 min. Two patients did not require any clamping. Overall, no transfusions were necessary, and there were no intraoperative complications or adverse postoperative clinical events. All margins were negative, and all patients were disease-free at the 6-month follow-up. CONCLUSIONS: Robotic-assisted laparoscopic partial nephrectomy is a feasible and safe approach to small renal cortical masses.Further prospective studies are needed to compare open partial nephrectomy with

  14. New similarity search based glioma grading

    Haegler, Katrin; Brueckmann, Hartmut; Linn, Jennifer [Ludwig-Maximilians-University of Munich, Department of Neuroradiology, Munich (Germany); Wiesmann, Martin; Freiherr, Jessica [RWTH Aachen University, Department of Neuroradiology, Aachen (Germany); Boehm, Christian [Ludwig-Maximilians-University of Munich, Department of Computer Science, Munich (Germany); Schnell, Oliver; Tonn, Joerg-Christian [Ludwig-Maximilians-University of Munich, Department of Neurosurgery, Munich (Germany)


    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone. (orig.)

  15. Immunoglobulin genes implicated in glioma risk.

    Pandey, Janardan P; Kaur, Navtej; Costa, Sandra; Amorim, Julia; Nabico, Rui; Linhares, Paulo; Vaz, Rui; Viana-Pereira, Marta; Reis, Rui M


    Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.

  16. Percutaneous transcatheter closure of atrial septal defects: initial single-centre experience and follow-up results. Initial experience with three-dimensional echocardiography.

    De Ridder, Serge; Suttorp, Maarten-Jan; Ernst, Sjef M P G; Six, Jacob A; Mannaerts, Herman F J; Kamp, Otto; Plokker, Thijs H W M; Jaarsma, Wybren


    Registry to report our single-centre experience in closing defects of the atrial septum. Between 1996 and 2001, transcatheter device closure of significant atrial septal defects was performed in 32 adults (mean age 45.1 years, range from 15 to 76 years), using different device types. Six patients had a patent foramen ovale (PFO) and 26 patients had a secundum atrial septal defect (ASD II). Defects were selected by means of two-dimensional transoesophageal echocardiography (2D TOE). For 12 defects additional three-dimensional transoesophageal echocardiography (3D TOE) was performed. Mean balloon-stretched diameter was 19.3 mm (range from 11 to 24 mm). A device was successfully placed in all PFO patients (100%) without complications at follow-up. Successful immediate device placement occurred in 24 out of 26 ASD patients. Two immediate placement failures, 1 device embolisation and 1 device non-fixation, occurred and required urgent surgery. There was 1 patient with pericardial effusion after the intervention, requiring pericardiocentesis. Three late placement failures occurred: 2 device embolisations and 1 device dislocation. Clinical success after 3 to 6 months follow-up, defined as the absence of shunt or small shunt, was achieved in all 6 PFO patients and in 21 out of 23 ASD patients (1 device embolisation, requiring surgery, occurred before follow-up was completed). Two patients with significant shunt, 1 late device dislocation and 1 late device embolisation, underwent elective surgery. For patient selection, 3D TOE proved useful in the evaluation of large and/or complex defects. Transcatheter device closure of carefully selected atrial septal defects is an alternative to surgery. Although the results are promising, surgical back-up is often needed.

  17. The role of extracellular matrix in glioma invasion: a cellular Potts model approach.

    Rubenstein, Brenda M; Kaufman, Laura J


    In this work, a cellular Potts model based on the differential adhesion hypothesis is employed to analyze the relative importance of select cell-cell and cell-extracellular matrix (ECM) contacts in glioma invasion. To perform these simulations, three types of cells and two ECM components are included. The inclusion of explicit ECM with an inhomogeneous fibrous component and a homogeneously dispersed afibrous component allows exploration of the importance of relative energies of cell-cell and cell-ECM contacts in a variety of environments relevant to in vitro and in vivo experimental investigations of glioma invasion. Simulations performed here focus chiefly on reproducing findings of in vitro experiments on glioma spheroids embedded in collagen I gels. For a given range and set ordering of energies associated with key cell-cell and cell-ECM interactions, our model qualitatively reproduces the dispersed glioma invasion patterns found for most glioma cell lines embedded as spheroids in collagen I gels of moderate concentration. In our model, we find that invasion is maximized at intermediate collagen concentrations, as occurs experimentally. This effect is seen more strongly in model gels composed of short collagen fibers than in those composed of long fibers, which retain significant connectivity even at low density. Additional simulations in aligned model matrices further elucidate how matrix structure dictates invasive patterns. Finally, simulations that allow invading cells to both dissolve and deposit ECM components demonstrate how Q-Potts models may be elaborated to allow active cell alteration of their surroundings. The model employed here provides a quantitative framework with which to bound the relative values of cell-cell and cell-ECM interactions and investigate how varying the magnitude and type of these interactions, as well as ECM structure, could potentially curtail glioma invasion.

  18. Greening of a Campus through Waste Management Initiatives: Experience from a Higher Education Institution in Thailand

    Tangwanichagapong, Siwaporn; Nitivattananon, Vilas; Mohanty, Brahmanand; Visvanathan, Chettiyappan


    Purpose: This paper aims to describe the effects of 3R (reduce, reuse and recycle) waste management initiatives on a campus community. It ascertains the environmental attitudes and opinions of the residents and investigates their behavioral responses to waste management initiatives. Practical implications for enhancing sustainable waste management…

  19. Project Description Advanced Fuel Cycle Initiative AFC-2A and AFC-2B Experiments

    AFCI AFC-2A and AFC-2B Experiments Project Executi


    The proposed AFC-2A and AFC-2B irradiation experiments are a continuation of the AFC-1 fuel test series currently in progress in the ATR. This document discusses the experiments and the planned activities that will take place.

  20. Molecular Therapeutic Targets for Glioma Angiogenesis

    Shingo Takano


    Full Text Available Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, v3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4 results in a nonfunctioning vasculature and could be another important target distinct from VEGF.

  1. Genetic characterization of adult infratentorial gliomas.

    Miwa, Tomoru; Hirose, Yuichi; Sasaki, Hikaru; Ikeda, Eiji; Yoshida, Kazunari; Kawase, Takeshi


    Adult infratentorial gliomas are rare and have not been well studied. We therefore conducted genetic analysis of those tumors to see if there was any characteristic that could be relevant in clinical management and understanding of tumorigenesis. Nineteen adult infratentorial gliomas were analyzed for chromosomal aberration by comparative genomic hybridization, and for expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry. The most frequent chromosomal aberration was the gain of 7p, and five of the seven cerebellar or fourth ventricle malignant gliomas had that aberration. However, the gain of 7q, the characteristic abnormality of supratentorial astrocytomas commonly associated with the gaining of 7p, was observed only in 1 of 11 adult infratentorial astrocytic tumors. Combined losses of 1p and 19q, the genetic hallmark of oligodendroglioma, were not observed. Results of immunohistochemistry of p53 and EGFR were comparable to those reported in supratentorial gliomas. Our findings might suggest the presence of distinct tumorigenic pathway in adult infratentorial gliomas.

  2. Sensitivity of Interstitial combined Chemotherapy against Glioma

    WANG Ming-sheng; LIN Jian-ying; ZHOU Guo-sheng; ZHANG Xin-zhong


    Objective To investigate the inhibitory effects of combination chemotherapy of Carboplatin(CBP) ,Teniposide (Vm-26) ,Methasquin(MTX),and Nimodipine(NIM) on glioma,and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells,and to compare the sensitivity of glioma cells to administration of CBP,Vm-26, MTX, and NIM with that of the administration of CBP + NIM, Vm-26 + NIM, MTX + NIM, CBP + Vm-26 + MTX, or CBP + Vm-26 + MTX + NIM respectively. Results The inhibition rate of CBP + Vm-26 + MTX + NIM combination administration against glioma cells was 96.64%,which was higher than that of CBP + NIM (69.03%), Vm-26 + NIM (71.53%), MTX + NIM (52. 75% ), CBP + Vm-26 + MTX(78.59%)(P<0.01),and the dosage of CBP,Vm-26,and MTX was declined to 1/10 ~ 1/100 that of respective use of CBP,Vm-26,and MTX. Conclusions The curative effects of combination administration of CBP,Vm-26, MTX, and NIM was much better than that of respective administration,suggesting a higher inhibition rate and a lower dosage use.

  3. Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

    Holz David


    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

  4. Initial Experience of Transurethral Resection with Pediatric Resectoscope for Incomplete Anterior Urethral Stricture

    Won Seok Jang


    Full Text Available Purpose Endoscopic urethrotomy is an alternative method in treatment of urethral stricture. However, it have high recurrence rate because of the remained fibrotic tissue. Removal of the fibrotic tissue can maintain the patency of the urethral lumen after the procedure. We report the therapeutic efficacy of our initial experience using pediatric resectoscope for treating anterior urethral stricture in 16 cases. Materials and Methods From January 2009 to April 2011, transurethral resection with pediatric resectoscope was primarily performed on 16 patients with anterior urethral stricture. Retrograde urethrography, uroflowmetry, postvoid residual volume, IPSS score and QoL score were performed preoperatively. We used 11.5Fr pediatric resectoscope (Wolf and monopolar electrosurgical generator. The stricture was incised under vision at the 12 o'clock location or the site of maximum scar tissue or narrowing in asymmetric strictures for working space. After incision, transurethral resection with pediatric resectoscope was performed to all scar tissues. Monopolar cutting current was set on 45 watt and coagulation current was set on 30 watt, fulgurate mode. Postoperatively, drainage of the bladder was performed for 7 days using an 18F latex catheter. Patients were followed up by IPSS score, QoL score, uroflowmetry and postvoid residual volume. Results Successful results without recurrence were achieved in 11 of 16patients. Postoperative urethral dilation had been performed average 2.4 times (0∼6 times. When we classified the results by etiology, the number of successful results in strictures with a trauma, iatrogenic, or unknown cause was 5 (7/11, 3 (3/4 and 1 (1/1, respectively. In 5 patients who failed treatment, we repeated transurethral resection with pediatric resectoscope in 1 patient, and periodic urethral dilation in 4 patients. No operative complications occurred in any patients. Conclusions Transurethral resection with pediatric resectoscope

  5. Supporting ITM Missions by Observing System Simulation Experiments: Initial Design, Challenges and Perspectives

    Yudin, V. A.; England, S.; Matsuo, T.; Wang, H.; Immel, T. J.; Eastes, R.; Akmaev, R. A.; Goncharenko, L. P.; Fuller-Rowell, T. J.; Liu, H.; Solomon, S. C.; Wu, Q.


    We review and discuss the capability of novel configurations of global community (WACCM-X and TIME-GCM) and planned-operational (WAM) models to support current and forthcoming space-borne missions to monitor the dynamics and composition of the Ionosphere-Thermosphere-Mesosphere (ITM) system. In the specified meteorology model configuration of WACCM-X, the lower atmosphere is constrained by operational analyses and/or short-term forecasts provided by the Goddard Earth Observing System (GEOS-5) of GMAO/NASA/GSFC. With the terrestrial weather of GEOS-5 and updated model physics, WACCM-X simulations are capable to reproduce the observed signatures of the perturbed wave dynamics and ion-neutral coupling during recent (2006-2013) stratospheric warming events, short-term, annual and year-to-year variability of prevailing flows, planetary waves, tides, and composition. With assimilation of the NWP data in the troposphere and stratosphere the planned-operational configuration of WAM can also recreate the observed features of the ITM day-to-day variability. These "terrestrial-weather" driven whole atmosphere simulations, with day-to-day variable solar and geomagnetic inputs, can provide specification of the background state (first guess) and errors for the inverse algorithms of forthcoming NASA ITM missions, such as ICON and GOLD. With two different viewing geometries (sun-synchronous, for ICON and geostationary for GOLD) these missions promise to perform complimentary global observations of temperature, winds and constituents to constrain the first-principle space weather forecast models. The paper will discuss initial designs of Observing System Simulation Experiments (OSSE) in the coupled simulations of TIME-GCM/WACCM-X/GEOS5 and WAM/GIP. As recognized, OSSE represent an excellent learning tool for designing and evaluating observing capabilities of novel sensors. The choice of assimilation schemes, forecast and observational errors will be discussed along with challenges

  6. Myocardial stress perfusion magnetic resonance: initial experience in a pediatric and young adult population using regadenoson

    Noel, Cory V. [Baylor College of Medicine, Department of Pediatric Cardiology, Houston, TX (United States); Texas Children' s Hospital, Department of Pediatric Cardiology, Houston, TX (United States); Krishnamurthy, Ramkumar; Krishnamurthy, Rajesh [Texas Children' s Hospital, Department of Radiology, Houston, TX (United States); Moffett, Brady [Texas Children' s Hospital, Department of Pharmacology, Houston, TX (United States)


    Dipyridamole and adenosine are traditional pharmacological stressors for myocardial perfusion. Regadenoson, a selective adenosine A2A agonist, has a lower side effect profile with lower incidence of bronchospasm and bradycardia. There is a growing need for myocardial perfusion assessment within pediatrics. There is no report on the utility of regadenoson as a stress agent in children. To observe the safety and feasibility of regadenoson as a pharmacologic stressor for perfusion cardiac MR in a pilot cohort of pediatric patients weighing more than 40 kg who have congenital heart disease and pediatric acquired heart disease. We reviewed our initial experience with regadenoson stress cardiac MR in 31 pediatric patients 15.8 ± 1.7 years (range 12-22 years) with congenital heart disease and acquired heart disease. Mean patient weight was 60 ± 15 kg (range of 40-93 kg). All patients underwent cardiac MR because of concern for ischemia. The cohort included a heterogeneous group of patients at a pediatric institution with potential risk for ischemia. Subjects' heart rate and blood pressure were monitored and pharmacologic stress was induced by injection of 400 mcg of regadenoson. We evaluated their hemodynamic response and adverse effects using changes in vital signs and onset of symptoms. A pediatric cardiologist and radiologist qualitatively assessed myocardial perfusion and viability images. One child was unable to complete the stress perfusion portion of the examination, but did complete the remaining portion of the CMR. Resting heart rate was 72 ± 14 beats per minute (bpm) and rose to peak of 124 ± 17 bpm (95 ± 50% increase, P < 0.005) with regadenoson. Image quality was considered good or diagnostic in all cases. Three patients had irreversible perfusion defects. Four patients had reversible perfusion defects. Nine of the patients underwent cardiac catheterization with angiography and the findings showed excellent agreement. Regadenoson might be a safe and

  7. Initial experiences of implementation of functional integration (FI) in LEPRA India projects in Orissa.

    Rao, V Prabhakara; Bhuskade, R A; Raju, M Sathi; Rao, P V Ranganadha; Desikan, K V


    In 2000, the Government of the State of Orissa (population 37 million) in India decided to introduce functional integration for the control of leprosy, in place of the long-established vertical programme, using the general health services and the primary health care system. This paper describes the initial (9 months) experience of implementing this strategy in two projects run by LEPRA India. One of these, in the district of Koraput, was established in 1991 and covers a population of 1.5 million people. The other, in Kalahandi district, started in 1997 and covers a population of 600,000. Both projects operate under difficult conditions with regard to terrain, the use of numerous tribal languages, illiteracy, water shortage, poor roads and communications. The preparatory phase included intensive health education of the public on leprosy, using a wide range of educational media and techniques. At the same time, LEPRA India supported the Government in the training and orientation of trainers, medical officers, primary health care staff and female health workers at village level. In all, over 2000 were trained. This paper describes all aspects of the implementation of functional integration in these two areas. In the 9-month period, 4207 suspect cases were referred to medical officers by health workers, but only 256 (6%) were confirmed as having leprosy. There were 169 confirmed self-reporting cases. Despite the clearly understood intention to involve primary health staff in case detection, 67% of all cases were in fact detected by LEPRA India, possibly due to overlapping attendance at clinics by vertical and general staff. There is obviously a need for further training of the general staff since only 6% of cases referred by them were confirmed as having leprosy. Steps must also be taken to ensure that the emphasis on case detection, confirmation and treatment shifts from the vertical to the general health staff. The supply of anti-leprosy drugs and steroids to primary

  8. E-learning course: Basis of Harvest and Preservation of Tissues – design and initial experience

    Pavel Měřička


    Full Text Available Background: The design and initial experience with the e-learning course “Basis of Harvest and Preservation of Tissues” used as a support of an elective subject is presented. The aim of the e-learning course was to enable the students to learn the theoretical principles of the subject individually and to present the gained knowledge at the final seminar. Methods: All functions of the course were operated in Moodle, local application of the Charles University in Prague, Faculty of Medicine in Hradec Králové. The course was divided into 3 main topics corresponding with topics of lectures: 1. Principles of tissue and organ donation, 2. Low temperature preservation of cells, tissues and organs, 3. Quality and safety assurance in practice of tissue and procurement establishments. A test consisting of 5 questions selected randomly from the bank of questions followed each topic. If the student answers correctly at least 3 questions he is allowed to pass to the next topic. The fourth topic “Basic processes in the tissue establishment and principles of their validation” was added into the electronic version as a tool for repeating and improving of knowledge. The fifth topic was represented by a database for uploading theses presented by students at the final seminar. The final test consisted of 15 questions (5 ones from each basic topic. It was necessary to answer correctly at least 10 questions to receive a certificate of completing the course. Results: The course was put into operation during the summer term of the academic year 2012/2013. To the date 15 of September the total of 23 students enrolled (17, i.e. all students of the elective subject in the Czech version, 2 students of this subject in the English version, 2 postgraduate students and 2 medical doctors. All enrolled students used the course for on-line learning, downloading, or printing course study materials. All undergraduate students were obliged to use it for preparation

  9. An initial experience with a digital drainage system during the postoperative period of pediatric thoracic surgery.

    Costa, Altair da Silva; Bachichi, Thiago; Holanda, Caio; Rizzo, Luiz Augusto Lucas Martins De


    To report an initial experience with a digital drainage system during the postoperative period of pediatric thoracic surgery. This was a prospective observational study involving consecutive patients, ≤ 14 years of age, treated at a pediatric thoracic surgery outpatient clinic, for whom pulmonary resection (lobectomy or segmentectomy via muscle-sparing thoracotomy) was indicated. The parameters evaluated were air leak (as quantified with the digital system), biosafety, duration of drainage, length of hospital stay, and complications. The digital system was used in 11 children (mean age, 5.9 ± 3.3 years). The mean length of hospital stay was 4.9 ± 2.6 days, the mean duration of drainage was 2.5 ± 0.7 days, and the mean drainage volume was 270.4 ± 166.7 mL. The mean maximum air leak flow was 92.78 ± 95.83 mL/min (range, 18-338 mL/min). Two patients developed postoperative complications (atelectasis and pneumonia, respectively). The use of this digital system facilitated the decision-making process during the postoperative period, reducing the risk of errors in the interpretation and management of air leaks. Relatar a experiência inicial com um sistema de drenagem digital no pós-operatório de cirurgia torácica pediátrica. Estudo observacional e prospectivo envolvendo pacientes consecutivos do ambulatório de cirurgia torácica pediátrica da instituição, com idade até 14 anos, e com indicação de ressecção pulmonar (lobectomia e/ou segmentectomia através de toracotomia poupadora muscular). Os parâmetros avaliados foram perda aérea (quantificada com o sistema digital), biossegurança, tempo de drenagem, tempo de internação e complicações. O sistema digital foi utilizado em 11 crianças, com média de idade de 5,9 ± 3,3 anos. A média do tempo de internação foi de 4,9 ± 2,6 dias, a de tempo de drenagem foi de 2,5 ± 0,7 dias, e a de volume de drenagem foi de 270,4 ± 166,7 ml. A média da perda aérea máxima foi de 92,78 ± 95,83 ml

  10. Characterizing Design Cognition of High School Students: Initial Analyses Comparing Those with and without Pre-Engineering Experiences

    Wells, John; Lammi, Matthew; Gero, John; Grubbs, Michael E.; Paretti, Marie; Williams, Christopher


    Reported in this article are initial results from of a longitudinal study to characterize the design cognition and cognitive design styles of high school students with and without pre-engineering course experience over a 2-year period, and to compare them with undergraduate engineering students. The research followed a verbal protocol analysis…

  11. The Relationship of a Pilot's Educational Background, Aeronautical Experience and Recency of Experience to Performance In Initial Training at a Regional Airline

    Shane, Nancy R.

    The purpose of this study was to determine how a pilot's educational background, aeronautical experience and recency of experience relate to their performance during initial training at a regional airline. Results show that variables in pilots' educational background, aeronautical experience and recency of experience do predict performance in training. The most significant predictors include years since graduation from college, multi-engine time, total time and whether or not a pilot had military flying experience. Due to the pilot shortage, the pilots entering regional airline training classes since August 2013 have varied backgrounds, aeronautical experience and recency of experience. As explained by Edward Thorndike's law of exercise and the law of recency, pilots who are actively using their aeronautical knowledge and exercising their flying skills should exhibit strong performance in those areas and pilots who have not been actively using their aeronautical knowledge and exercising their flying skills should exhibit degraded performance in those areas. Through correlation, chi-square and multiple regression analysis, this study tests this theory as it relates to performance in initial training at a regional airline.

  12. Treatment of malignant glioma using hyperthermia*

    Jiahang Sun; Mian Guo; Hengyuan Pang; Jingtao Qi; Jinwei Zhang; Yunlong Ge


    Thirty pathological y diagnosed patients with grade III-IV primary or recurrent malignant glioma (tumor diameter 3-7 cm) were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com-bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. During 3 months after hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper-thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80%of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra-dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.

  13. Ki-67 overexpression in WHO grade II gliomas is associated with poor postoperative seizure control.

    Yuan, Yang; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shuang, Liu; Yingjun, Fan; Qiao, Zhou; Yanwu, Yang; Qing, Mao


    Seizures are the most common initial symptom in patients with low-grade gliomas, and approximately 30% of these patients still suffer from epilepsy after gross-total resection of the tumour. We examined the relationship between the overexpression of ki-67 in WHO grade II gliomas and seizure control. A series of 93 histologically confirmed WHO grade II glioma tissues were analysed through immunohistochemical staining for ki-67 expression. Follow-up visits regarding seizure control were scheduled at 12 months. The Engel classification was used to categorise patients' seizure status. Of the 93 patients analysed, 65 (66.3%) patients initially presented with seizures. A total of 36 patients were diagnosed with WHO grade II oligodendrogliomas, 29 patients had oligoastrocytomas and 28 patients had astrocytomas. Ki-67 was over-expressed in 15 patients. One year after surgery poor seizure control was observed in 11 of these patients. In contrast, low ki-67 expression (seizure control was observed in 36 patients (difference between ki-67 over- and low expression groups P = 0.002). Logistic regression analysis revealed that patients with gross-total resection achieved better seizure control while ki-67 overexpression and age below 38 years were poor seizure control factors explained of the variance of seizure outcome (OR: 0.382, 4.354 and 1.822, respectively). In WHO grade II gliomas, Ki-67 is a molecular marker which predicts poor seizure control of glioma patients after the resection of the tumour. Gross-total resection, ki-67 overexpression and age below 38 years significantly affect seizure prognosis. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Initial experiments on the effectiveness of telephone access to government services

    Cloete, Jacob PL


    Full Text Available - and post-experiment interviews and an observed experiment. The experiments were performed at the Department of Labour in Pretoria, South Africa, in November 2003. Unscreened participants were solicited from the queue of UIF applicants. 14 callers used..., a number of conclusions were reached. Although transaction- completion rates were comparable for the speech-input and DTMF systems, users were much more comfortable with the speech-based system as reflected in somewhat higher user-satisfaction...

  15. Characteristics of gliomas in patients with somatic IDH mosaicism.

    Bonnet, Charlotte; Thomas, Laure; Psimaras, Dimitri; Bielle, Franck; Vauléon, Elodie; Loiseau, Hugues; Cartalat-Carel, Stéphanie; Meyronet, David; Dehais, Caroline; Honnorat, Jérôme; Sanson, Marc; Ducray, François


    IDH mutations are found in the majority of adult, diffuse, low-grade and anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier disease and Maffucci syndrome are two enchondromatosis syndromes characterized by the development of multiple benign cartilaginous tumors due to post-zygotic acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis patients sometimes develop gliomas. The aim of the present study was to determine whether gliomas in enchondromatosis patients might also result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH mutated gliomas, enchondromatosis gliomas were frequently located in the frontal lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21 %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p mosaicism and that the timing of IDH mutation acquisition might affect the location and molecular characteristics of gliomas. Early acquisition of IDH mutations could shift gliomagenesis towards the brainstem thereby mimicking the regional preference of histone mutated gliomas.

  16. [Surgical treatment of chiasmal gliomas in children].

    Helcl, F


    Chiasmal gliomas are rare brain tumors occurring especially in children. Their proper treatment is still controversial and consists of surgery, radiotherapy and chemotherapy. Surgical removal of these tumors can usually be only partial or subtotal and radiotherapy frequently follows. There are supporters of surgical approach, as well as its enemies. The author has been engaged in problems of optimal treatment of this entity for more than 10 years. He is offering a review of knowledge from the literature concerning surgical treatment of this disease in children. The great majority of articles in the literature are dealing with retrospective analysis of relatively small series of patients usually treated in single neurosurgical department and the surgical treatment is enclosed like a part of combined therapy. Articles dealing only with surgical treatment of chiasmal gliomas are few and reviews determining the contemporary role of surgery of this entity are also lacking. This was the main impulse for writing this compilation. The short history of surgical therapy is reviewed. Some new trends of this therapy are also mentioned (microsurgery, Cavitron Ultrasonic Surgical Aspirator and peroperative use of visual evoked potentials). Up to date criteria for surgical treatment of chiasmal gliomas in children are given-exploration of chiasmal region and performing a biopsy in all cases, radical surgery only in extrinsic gliomas of the chiasmal region and conservative surgical approach to intrinsic chiasmal gliomas. It is emphasized that the significance of obstructive hydrocephalus in this entity has not been fully estimated till now, as well as the role of shunting procedures. Surgical treatment remains, nevertheless, an important armamentarium in the management of chiasmal gliomas in children. (Ref. 20.)

  17. Molecular Alterations of KIT Oncogene in Gliomas

    Ana L. Gomes


    Full Text Available Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK, is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117 immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17 and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH and quantitative real-time PCR (qRT-PCR were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179 of cases, namely in 25% (1/4 of pilocytic astrocytomas, 25% (5/20 of diffuse astrocytomas, 20% (1/5 of anaplastic astrocytomas, 19.5% (15/77 of glioblastomas and one third (3/9 of anaplastic oligoastrocytomas. Only 5.7% (2/35 of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0–22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24 of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK

  18. Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma.

    Agnihotri, Sameer; Aldape, Kenneth D; Zadeh, Gelareh


    Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1-mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.

  19. Sensitivity Experiments of an Eastward-Moving Southwest Vortex to Initial Perturbations

    王智; 高坤


    Whether the initial conditions contain pronounced mesoscale signals is important to the simulation of the southwest vortex. An eastward-moving southwest vortex is simulated using the PSU/NCAR MM5. A modest degree of success is achieved, but the most serious failure is that the formation and displacement of the simulated vortex in its early phase are about fourteen hours later than the observed vortex. Considering the relatively sparse data on the mesoscale vortex and in an attempt to understand the cause of the forecast failure, an adjoint model is used to examine the sensitivity of the southwest vortex to perturbations of initial conditions. The adjoint sensitivity indicates how small perturbations of model variables at the initial time in the model domain can influence the vortex. A large sensitivity for zonal wind is located under 400 hPa, a large sensitivity for meridional wind is located under 500 hPa, a large sensitivity for temperature is located between 500 and 900 hPa, and almost all of the large sensitivity areas are located in the southwestern area. Based on the adjoint sensitivity results, perturbations are added to initial conditions to improve the simulation of the southwest vortex. The results show that the initial conditions with perturbations can successfully simulate the formation and displacement of the vortex; the wind perturbations added to the initial conditions appear to be a cyclone circulation under the middle level of the atmosphere in the southwestern area with an anticyclone circulation to its southwest; a water vapor perturbation added to initial conditions can strengthen the vortex and the speed of its displacement.

  20. Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma

    Oren J Becher


    Full Text Available Diffuse Intrinsic Pontine Glioma (DIPG is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of six and eight. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab, as well as to potentially treat them in the clinic. This review will detail the initial strides towards modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Lastly, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients.

  1. Molecular targeting for malignant gliomas (Review).

    Kondo, Yasuko; Hollingsworth, Emporia F; Kondo, Seiji


    With tendency to invade rapidly in the brain, malignant gliomas are very resistant to conventional therapies including radiation and chemotherapy. Recent advances in genetic and molecular techniques have made it possible to define characteristic molecular profiles of malignant gliomas. Based on the list of the molecules closely related to glioblastoma tissues, we reviewed strategies targeting them. Target molecules extensively studied include EGFR, PTEN, telomerase and signal pathway modulators for Ras/Raf/MAPK and PI3K/Akt/mTOR pathways. Therapies targeting specific molecules may result in killing tumor cells effectively while keeping normal cells intact.

  2. Using bioluminescence imaging in glioma research.

    Luwor, Rodney B; Stylli, Stanley S; Kaye, Andrew H


    Glioblastoma multiforme (GBM) is the most common malignant brain tumour and has the worst prognosis. Over the last decade, the use of bioluminescence imaging technology has rapidly become widespread to further understand the mechanisms that drive GBM development and progression. Pre-clinical evaluation and optimisation of therapeutic efficacy in GBM research has also utilised this simple non-invasive technology. Here we summarise recent advances made in glioma biology and therapeutic intervention using bioluminescence imaging. This review also describes the current knowledge regarding the use of luciferase-based reporters in examining the role of specific cancer signalling cascades that promote glioma progression.

  3. Reproducibility of scratch assays is affected by the initial degree of confluence: Experiments, modelling and model selection.

    Jin, Wang; Shah, Esha T; Penington, Catherine J; McCue, Scott W; Chopin, Lisa K; Simpson, Matthew J


    Scratch assays are difficult to reproduce. Here we identify a previously overlooked source of variability which could partially explain this difficulty. We analyse a suite of scratch assays in which we vary the initial degree of confluence (initial cell density). Our results indicate that the rate of re-colonisation is very sensitive to the initial density. To quantify the relative roles of cell migration and proliferation, we calibrate the solution of the Fisher-Kolmogorov model to cell density profiles to provide estimates of the cell diffusivity, D, and the cell proliferation rate, λ. This procedure indicates that the estimates of D and λ are very sensitive to the initial density. This dependence suggests that the Fisher-Kolmogorov model does not accurately represent the details of the collective cell spreading process, since this model assumes that D and λ are constants that ought to be independent of the initial density. Since higher initial cell density leads to enhanced spreading, we also calibrate the solution of the Porous-Fisher model to the data as this model assumes that the cell flux is an increasing function of the cell density. Estimates of D and λ associated with the Porous-Fisher model are less sensitive to the initial density, suggesting that the Porous-Fisher model provides a better description of the experiments.

  4. Seventh Fleet field training exercise : Fleet Battle Experiment Kilo : fires initiatives final report

    Schacher, G. E.; Pilnick, Steve; Irvine, Nelson; Gallup, Shelley


    Fleet Battle Experiment Kilo was conducted during Seventh Fleet exercise Tandem Thrust 03. During the Field Training Exercise phase, testing of Time Sensitive Targets processes using the Joint Fires Network was carried out. This report contains results obtained on contributions made by the Joint Fires Network to Navy Time Sensitive Targeting and experiment lessons learned. NA

  5. Eating at worksites in Nordic countries: national experiences and policy initiatives

    Jørgensen, Michael Søgaard; Arsky, Gunn Helene; Brandhøj, Mia


    with healthier worksite eating schemes based on employee participation can change the worksite eating substantially, also at blue-collar worksites. However, the dissemination to other worksites not participating in experiments seems limited. There is need for more research in the embedding of experiments...

  6. Initial Results on Neutralized Drift Compression Experiments (NDCX-IA) for High Intensity Ion Beam

    Roy, Prabir K; Baca, David; Bieniosek, Frank; Coleman, Joshua E; Davidson, Ronald C; Efthimion, Philip; Eylon, Shmuel; Gilson, Erik P; Grant Logan, B; Greenway, Wayne; Henestroza, Enrique; Kaganovich, Igor D; Leitner, Matthaeus; Rose, David; Sefkow, Adam; Sharp, William M; Shuman, Derek; Thoma, Carsten H; Vanecek, David; Waldron, William; Welch, Dale; Yu, Simon


    Ion beam neutralization and compression experiments are designed to determine the feasibility of using compressed high intensity ion beams for high energy density physics (HEDP) experiments and for inertial fusion power. To quantitatively ascertain the various mechanisms and methods for beam compression, the Neutralized Drift Compression Experiment (NDCX) facility is being constructed at Lawrence Berkeley National Laboratory (LBNL). In the first compression experiment, a 260 KeV, 25 mA, K+ ion beam of centimeters size is radially compressed to a mm size spot by neutralization in a meter-long plasma column and beam peak current is longitudinally compressed by an induction velocity tilt core. Instrumentation, preliminary results of the experiments, and practical limits of compression are presented. These include parameters such as emittance, degree of neutralization, velocity tilt time profile, and accuracy of measurements (fast and spatially high resolution diagnostic) are discussed.

  7. The anti-tumor effects of calorie restriction are correlated with reduced oxidative stress in ENU-induced gliomas

    Megan A. Mahlke


    Full Text Available The anti-tumor effects of calorie restriction (CR and the possible underlying mechanisms were investigated using ethylnitrosourea (ENU-induced glioma in rats. ENU was given transplacentally at gestational day 15, and male offspring were used in this experiment. The brain from 4-, 6-, and 8-month-old rats fed either ad libitum (AL or calorie-restricted diets (40% restriction of total calories compared to AL rats was studied. Tumor burden was assessed by comparing the number and size of gliomas present in sections of the brain. Immunohistochemical analysis was used to document lipid peroxidation [4-hydroxy-2-nonenal (HNE and malondialdehyde (MDA], protein oxidation (nitrotyrosine, glycation and AGE formation [methylglyoxal (MG and carboxymethyllysine (CML], cell proliferation activity [proliferating cell nuclear antigen (PCNA], cell death [single-stranded DNA (ssDNA], presence of thioredoxin 1 (Trx1, and presence of heme oxygenase-1 (HO-1 associated with the development of gliomas. The results showed that the number of gliomas did not change with age in the AL groups; however, the average size of the gliomas was significantly larger in the 8-month-old group compared to that of the younger groups. Immunopositivity was observed mainly in tumor cells and reactive astrocytes in all histological types of ENU-induced glioma. Immunopositive areas for HNE, MDA, nitrotyrosine, MG, CML, HO-1, and Trx1 increased with the growth of gliomas. The CR group showed both reduced number and size of gliomas, and tumors exhibited less accumulation of oxidative damage, decreased formation of glycated end products, and a decreased presence of HO-1 and Trx1 compared to the AL group. Furthermore, gliomas of the CR group showed less PCNA positive and more ssDNA positive cells, which are correlated to the retarded growth of tumors. Interestingly, we also discovered that the anti-tumor effects of CR were associated with decreased hypoxia-inducible factor-1α (HIF-1α levels

  8. 4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

    Ku, Bo Mi [Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751 (Korea, Republic of); Ryu, Hyung Won [Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture Life Science, Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Lee, Yeon Kyung; Ryu, Jinhyun; Jeong, Joo Yeon; Choi, Jungil [Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751 (Korea, Republic of); Cho, Hee Jun [Department of Microbiology, Research Institute of Life Science, College of Natureal Sciences, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Park, Ki Hun, E-mail: [Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture Life Science, Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Kang, Sang Soo, E-mail: [Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751 (Korea, Republic of)


    Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, and tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.

  9. Lymphoid Cell-Glioma Cell Interaction Enhances Cell Coat Production by Human Gliomas: Novel Suppressor Mechanism

    Dick, Steven J.; Macchi, Beatrice; Papazoglou, Savvas; Oldfield, Edward H.; Kornblith, Paul L.; Smith, Barry H.; Gately, Maurice K.


    Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

  10. PAR1 inhibition suppresses the self-renewal and growth of A2B5-defined glioma progenitor cells and their derived gliomas in vivo

    Auvergne, R.; Wu, C.; Connell, A.


    Glioblastoma (GBM) remains the most common and lethal intracranial tumor. In a comparison of gene expression by A2B5-defined tumor-initiating progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain, we found that the F2R gene encoding PAR1 was differentially overex...... the importance of PAR1 to the self-renewal and tumorigenicity of A2B5-defined glioma TPCs; as such, the abrogation of PAR1-dependent signaling pathways may prove a promising strategy for gliomas.[on SciFinder (R)]...

  11. Assessment of pain experience in adults and children after bracket bonding and initial archwire insertion

    Marcio José da Silva Campos


    Full Text Available INTRODUCTION: Ninety five percent of orthodontic patients routinely report pain, due to alterations in the periodontal ligament and surrounding soft tissues, with intensity and prevalence varying according to age. OBJECTIVE: This study aimed to assess toothache and buccal mucosal pain in adults and children during two initial phases of the orthodontic treatment. METHODS: The intensity of toothache and buccal mucosal pain reported by 20 patients, 10 children (11-13 years and 10 adults (18-37 years was recorded with the aid of a Visual Analog Scale (VAS, during 14 days - 7 days with bonded brackets only and 7 days with the initial archwire inserted. RESULTS: There was no significant difference in pain intensity among adults and children. After bracket bonding, 50% of the children and 70% of the adults reported pain. 70% of both groups reported pain after initial archwire insertion. While adults reported constant, low intensity, buccal mucosal pain, the children showed great variation of pain intensity, but with a trend towards decreasing pain during the assessment period. After initial archwire insertion the peaks of toothache intensity and prevalence occurred 24 hours in children and 48 hours in adults. CONCLUSIONS: In general, children reported pain less frequently than adults did, though with greater intensity.

  12. English as an Additional Language and Initial Teacher Education: Views and Experiences from Northern Ireland

    Skinner, Barbara


    This paper addresses training for teaching English as an Additional Language (EAL) at initial teacher education (ITE) level in Northern Ireland. This small-scale qualitative study describes 15 primary and post-primary teachers' perspectives on their preparation for teaching EAL in Northern Ireland. It explores reflections on EAL content in ITE…

  13. Robotics in hepatobiliary surgery-initial experience, first reported case series from India

    S. Goja


    Conclusion: This initial series adds to existing data on the feasibility of robotic hepatobiliary cases with inherent advantages of minimal invasive surgery, however with limitation of availability and use of devices like cavitron ultrasonic surgical aspirator (CUSA and higher operative cost.

  14. Experiments with Metadata-Derived Initial Values and Linesearch Bundle Adjustment in Architectural Photogrammetry

    Börlin, N.; Grussenmeyer, P.


    According to the Waldhäusl and Ogleby (1994) "3 x 3 rules", a well-designed close-range architectural photogrammetric project should include a sketch of the project site with the approximate position and viewing direction of each image. This orientation metadata is important to determine which part of the object each image covers. In principle, the metadata could be used as initial values for the camera external orientation (EO) parameters. However, this has rarely been used, partly due to convergence problem for the bundle adjustment procedure. In this paper we present a photogrammetric reconstruction pipeline based on classical methods and investigate if and how the linesearch bundle algorithm of Börlin et al. (2004) and/or metadata can be used to aid the reconstruction process in architectural photogrammetry when the classical methods fail. The primary initial values for the bundle are calculated by the five-point algorithm by Nistér (Stewénius et al., 2006). Should the bundle fail, initial values derived from metadata are calculated and used for a second bundle attempt. The pipeline was evaluated on an image set of the INSA building in Strasbourg. The data set includes mixed convex and non-convex subnetworks and a combination of manual and automatic measurements. The results show that, in general, the classical bundle algorithm with five-point initial values worked well. However, in cases where it did fail, linesearch bundle and/or metadata initial values did help. The presented approach is interesting for solving EO problems when the automatic orientation processes fail as well as to simplify keeping a link between the metadata containing the plan of how the project should have become and the actual reconstructed network as it turned out to be.

  15. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones.

    Benedetta Leuner

    Full Text Available Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute or once daily for 14 consecutive days (chronic and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated

  16. The Association between Some Nutrients and Adult Gliomas: A Case-Control Study of Adult Gliomas

    M Shayanfar


    Full Text Available Abestract Background & aim: It has been estimated that about 30–40 percent of all cancers could be prevented by diet and lifestyle. In the present study, associations between food groups and some nutrients were studied in adult glioma. Methods: In the present hospital-based case-control study which took place in Tehran, Iran, from 2010 to 2012, socio-economic information, demographics, lifestyle factors, health and dietary intakes of 128 patients with glioma as cases, and 256 healthy controls, were collected through interviews and questionnaires. Logistic regression was used to estimate odds ratios. SPSS version 19 was used for all statistical analyses. Results: After adjusting for potential confounders, inverse associations between calcium intake and adult glioma and vitamin C were observed. (Highest tertile versus lowest: OR = 0.20, 95% CI = 0.87-0.46, P for trend = 0.001 and vitamin C (OR = 0.34, 95% CI = 0.15-0.76, P for trend = 0.002. In addition, we observed elevated ORs for highest vs. lowest tertile of cholesterol intake (OR = 2.78, 95% CI = 1.29-5.99, P for trend = 0.061. We observed no significant associations with adult glioma for intakes of total fat, carbohydrate, protein, vitamin A, vitamin E and beta carotene. Conclusion: the results showed that intake of calcium and vitamin C may possibly prevent glioma in adults. Key words: Gliomas, Adult, Ca, Vitamin C

  17. Abnormal expressions of proliferating cell nuclear antigen and P27 protein in brain glioma


    BACKGROUND: Both proliferating cell nuclear antigen and P27 protein are important factors to regulate cell cycle. While, the combination of them can provide exactly objective markers to evaluate prognosis of patients with brain glioma needs to be further studied based on pathological level.OBJECTIVE: To observe the expressions of proliferating cell nuclear antigen and P27 protein in both injured and normal brain glioma tissues and analyze the effect of them on onset and development of brain glioma.DESIGN: Case contrast observation.SETTING: Department of Neurosurgery, the Second Affiliated Hospital of Xi'an Jiaotong University.PARTICIPANTS: A total of 63 patients with brain glioma were selected from Department of Neurosurgery,the Second Affiliated Hospital of Xi'an Jiaotong University from July 1996 to June 2000. There were 38 males and 25 females and their ages ranged from 23 to 71 years. Based on pathological classification and grading standards of brain glioma, patients were divided into grade Ⅰ - tⅡ (n =30) and grade Ⅲ - Ⅳ (n =33). All cases received one operation but no radiotherapy and chemiotherapy before operation. Sample tissues were collected from tumor parenchyma. Non-neoplastic brain tissues were collected from another 12 non-tumor subjects who received craniocerebral trauma infra-decompression and regarded as the control group. There were 10 males and 2 females and their ages ranged from 16 to 54 years. The experiment had got confirmed consent from local ethic committee and the collection was provided confirmed consent from patients and their relatives. All samples were restained with HE staining so as to diagnose as the brain glioma.While, all patients with brain glioma received radiotherapy after operation and their survival periods were followed up.METHODS: Primary lesion wax of brain glioma was cut into serial sections and stained with S-P immunohistochemical staining. Brown substance which was observed in tumor nucleus was regarded as the

  18. mir-300 promotes self-renewal and inhibits the differentiation of glioma stem-like cells

    Zhang, Daming


    MicroRNAs (miRNAs) are small noncoding RNAs that have been critically implicated in several human cancers. miRNAs are thought to participate in various biological processes, including proliferation, cell cycle, apoptosis, and even the regulation of the stemness properties of cancer stem cells. In this study, we explore the potential role of miR-300 in glioma stem-like cells (GSLCs). We isolated GSLCs from glioma biopsy specimens and identified the stemness properties of the cells through neurosphere formation assays, multilineage differentiation ability analysis, and immunofluorescence analysis of glioma stem cell markers. We found that miR-300 is commonly upregulated in glioma tissues, and the expression of miR-300 was higher in GSLCs. The results of functional experiments demonstrated that miR-300 can enhance the self-renewal of GSLCs and reduce differentiation toward both astrocyte and neural fates. In addition, LZTS2 is a direct target of miR-300. In conclusion, our results demonstrate the critical role of miR-300 in GSLCs and its functions in LZTS2 inhibition and describe a new approach for the molecular regulation of tumor stem cells. © 2014 Springer Science+Business Media.

  19. The Effect of Temozolomide/Poly(lactide-co-glycolide (PLGA/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior

    Anhua Wu


    Full Text Available In this study, we investigated the effects of temozolomide (TMZ/Poly (lactide-co-glycolide(PLGA/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.

  20. Next generation experiments and models for shock initiation and detonation of solid explosives

    Tarver, C M


    Current phenomenological hydrodynamic reactive flow models, such as Ignition and Growth and Johnson- Tang-Forest, when normalized to embedded gauge and laser velocimetry data, have been very successful in predicting shock initiation and detonation properties of solid explosives in most scenarios. However, since these models use reaction rates based on the compression and pressure of the reacting mixture, they can not easily model situations in which the local temperature, which controls the local reaction rate, changes differently from the local pressure. With the advent of larger, faster, parallel computers, microscopic modeling of the hot spot formation processes and Arrhenius chemical kinetic reaction rates that dominate shock initiation and detonation can now be attempted. Such a modeling effort can not be successful without nanosecond or better time resolved experimental data on these processes. The experimental and modeling approaches required to build the next generation of physically realistic reactive flow models are discussed.

  1. Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment

    Álvarez, V; Cárcel, S; Castel, J; Cebrián, S; Cervera, A; Conde, C A N; Dafni, T; Dias, T H V T; Díaz, J; Egorov, M; Esteve, R; Evtoukhovitch, P; Fernandes, L M P; Ferrario, P; Ferreira, A L; Freitas, E D C; Gehman, V M; Gil, A; Goldschmidt, A; Gómez, H; Gómez-Cadenas, J J; González-Díaz, D; Gutiérrez, R M; Hauptman, J; Morata, J A Hernando; Herrera, D C; Iguaz, F J; Irastorza, I G; Jinete, M A; Labarga, L; Laing, A; Liubarsky, I; Lopes, J A M; Lorca, D; Losada, M; Luzón, G; Marí, A; Martín-Albo, J; Martínez, A; Miller, T; Moiseenko, A; Monrabal, F; Monteiro, C M B; Mora, F J; Moutinho, L M; Vidal, J Muñoz; da Luz, H Natal; Navarro, G; Nebot, M; Nygren, D; Oliveira, C A B; Palma, R; Pérez, J; Aparicio, J L Pérez; Renner, J; Ripoll, L; Rodríguez, A; Rodríguez, J; Santos, F P; Santos, J M F dos; Segui, L; Serra, L; Shuman, D; Simón, A; Sofka, C; Sorel, M; Toledo, J F; Tomás, A; Torrent, J; Tsamalaidze, Z; Vázquez, D; Veloso, J F C A; Villar, J A; Webb, R; White, J T; Yahlali, N


    NEXT-DEMO is a large scale prototype and demonstrator of the NEXT-100 High Pressure Xenon Gas TPC, which will search for the neutrinoless double beta decay of Xe-136 using 100-150 kg of enriched xenon gas. The apparatus was built to prove the expected performance of NEXT-100, namely, energy resolution better than 1% FWHM at 2.5 MeV and event topological reconstruction. In this paper we describe the operation and initial results of the detector.

  2. Seeding Entrepreneurship Across Campus Early Implementation Experiences of the Kauffman Campuses Initiative

    Lara Hulsey; Linda Rosenberg; Benita Kim


    Entrepreneurship has long been a fundamental aspect of American society, serving as an important contributor to economic growth. However, only recently has entrepreneurship begun to develop as an academic field in U.S. colleges and universities. The Ewing Marion Kauffman Foundation launched the Kauffman Campuses Initiative in eight U.S. universities to encourage campuswide expansion of entrepreneurship programs and activities. This report provides a cross-site analysis of implementation exper...

  3. Initiating an Action Research Programme for University EFL Teachers: Early Experiences and Responses

    Anne Burns


    Full Text Available Accounts of how teacher educators begin to plan, develop, and support action research programmes for language teachers are rare, as are descriptions of the responses of the teachers who participate. This article documents and analyses the initial processes of introducing and supporting a new programme of action research for language teachers at the Universidad Chileno-Británica de Cultura (UCBC in Santiago, Chile. To evaluate the setting up of the programme and how the teachers have perceived it in its early stages, the authors, who are the programme facilitators, have conducted a meta- study. Data include workshop and meeting recordings, workshop observation notes, a reflective account, and a teacher questionnaire. The findings indicate that the teachers value the input and collaboration provided by an initial workshop, and subsequent meetings and discussions, very highly, but that issues of time, student involvement, and academic literature are areas for further debate and development. The article ends by drawing out the broader implications for UCBC and for others wishing to initiate similar action research programmes.

  4. Kynurenic acid synthesis by human glioma

    Vezzani, A; Gramsbergen, J B; Versari, P;


    Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40...

  5. Genetics and pharmacogenomics of diffuse gliomas

    Thuijl, H.F. van; Ylstra, B.; Wurdinger, T.; Nieuwenhuizen, D. van; Heimans, J.J.; Wesseling, P.; Reijneveld, J.C.


    Rapidly evolving techniques for analysis of the genome provide new opportunities for cancer therapy. For diffuse gliomas this has resulted in molecular markers with potential for personalized therapy. Some drugs that utilize pharmacogenomics are currently being tested in clinical trials. In melanoma

  6. Mean Diffusional Kurtosis in Patients with Glioma

    Tietze, A.; Hansen, Mikkel Bo; Østergaard, Leif


    , and the contralateral normal appearing white and grey matter of 34 patients (22 high-grade, 12 low-grade gliomas). MK’ and MD in different grades were compared using a Wilcoxon rank-sum test. Receiver Operating Characteristic curves and the area under the curve were calculated to determine the diagnostic accuracy of MK...

  7. Changing incidence and improved survival of gliomas

    Ho, Vincent K. Y.; Reijneveld, Jaap C.; Enting, Roeline; Bienfait, Henri P.; Robe, Pierre; Baumert, Brigitta G.; Visser, Otto


    BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma

  8. Neuromyelitis Optica Lesion Mimicking Brainstem Glioma

    J Gordon Millichap


    Full Text Available A 12-year-old girl who presented with weakness of the left extremities and right sided sixth cranial nerve palsy had neuromyelitis optica (NMO mistaken for brainstem glioma on MRI, in a report from Brain Research Institute, Yonsei University College of Medicine,Seoul, Republic of KoreaNeuromyelitis Optica, Optic-Spinal Syndrome, Spectroscopy.

  9. Hormone replacement therapy and risk of glioma

    Andersen, Lene; Friis, Søren; Hallas, Jesper;


    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  10. Surgical strategies for glioma involving language areas

    ZHANG Zhong; JIANG Tao; XIE Jian; LIU Fu-sheng; LI Shou-wei; QIAO Hui; WANG Zhong-cheng


    Background Successful treatment of gliomas in or adjacent to language areas constitutes a major challenge to neurosurgery. The present study was performed to evaluate the procedure of language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia when performed prior to resective glioma surgery.Methods Thirty patients with gliomas and left-hemisphere dominance and, who underwent language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia before resective glioma surgery, were analyzed retrospectively. All patients had tumors in or adjacent to cortical language areas. The brain lesions were removed according to anatomic-functional boundaries with preservation of areas of language function. Both preoperative and postoperative functional findings were evaluated.Results Intraoperative language areas were detected in 20 patients but not in four patients. Language mapping failure for reasons attributable to the anaesthesia or to an intraoperative increase in intracranial pressure occurred in six cases.Seven patients presented with moderate or severe language deficits after six months of follow-up. Total resection was achieved in 14 cases, near-total resection in 12 cases and subtotal resection in four cases.Conclusions Intraoperative cortical electrical stimulation is an accurate and safe approach to identification of the language cortex. Awake craniotomy intraoperative cortical electrical stimulation, in combination with presurgical neurological functional imaging to identify the anatomic-functional boundaries of tumor resection, permits extensive tumor excision while preserving normal language function and minimizing the risk of postoperative language deficits.

  11. Initial Experience of Laparoendoscopic Single-Site Radical Prostatectomy Requiring Well-Equipped Appliances and a Skilled Technique

    Joo Yong Lee


    Full Text Available We report an initial experience in laparoendoscopic single-site radical prostatectomy (LESSRP using a homemade single-port device for prostate cancer. A 63-year-old man was diagnosed with prostate cancer. The patient underwent LESSRP using an Alexis® wound retractor, which was inserted through an umbilical incision. A homemade single-port device was made by fixing a 61/2 surgical glove to the retractor’s outer ring and securing the glove finger to the end of 4 trocars with a tie. Using the flexible laparoscopic and rigid instruments, LESSRP was performed using a procedure similar to conventional laparoscopic radical prostatectomy (LRP. In the current case, we could not perform complete LESSRP, so we report our initial experience and consider the reason why laparoendoscopic single-site surgery was converted to conventional LRP.

  12. Initiation of Addiction Treatment and Access to Services: Young Adults' Accounts of Their Help-Seeking Experiences.

    Wagner, Vincent; Bertrand, Karine; Flores-Aranda, Jorge; Acier, Didier; Brunelle, Natacha; Landry, Michel; Brochu, Serge


    Substance addiction in young adults is particularly problematic. Yet, much remain at stake in understanding the specifics of this population's access to services. The objective of this study is to explore young adults' initiation of substance misuse treatment. Our study sample was composed of 35 individuals aged 18 to 30 with problematic psychoactive substance use who have been identified in criminal courts, hospital emergency departments, and Health and Social Services Centers in Québec (Canada). A thematic analysis was performed on the 62 semi-structured interviews conducted with participants. Three components emerged. First, personal elements-expectations, individual motivations, perceptions of use, and capacity to control it-influence initiation of substance misuse treatment. Second, family and peers have noticeable influences. Finally, system characteristics and prior care experiences also shape the process. Consideration should be given to tailor interventions that can reach young adults and encourage them to initiate appropriate care.

  13. Outcome of MRI-guided vacuum-assisted breast biopsy – initial experience at Institute of Oncology Ljubljana, Slovenia

    Zebic-Sinkovec, Marta; Hertl, Kristijana; Kadivec, Maksimiljan; Cavlek, Mihael; Podobnik, Gasper; Snoj, Marko


    Background. Like all breast imaging modalities MRI has limited specificity and the positive predictive value for lesions detected by MRI alone ranges between 15 and 50%. MRI guided procedures (needle biopsy, presurgical localisation) are mandatory for suspicious findings visible only at MRI, with potential influence on therapeutic decision. The aim of this retrospective study was to evaluate our initial clinical experience with MRI-guided vacuum-assisted breast biopsy as an alternative to sur...

  14. An Experience-Based Learning Framework: Activities for the Initial Development of Sustainability Competencies

    Caniglia, Guido; John, Beatrice; Kohler, Martin; Bellina, Leonie; Wiek, Arnim; Rojas, Christopher; Laubichler, Manfred D.; Lang, Daniel


    Purpose: This paper aims to present an experience-based learning framework that provides a bottom-up, student-centered entrance point for the development of systems thinking, normative and collaborative competencies in sustainability. Design/methodology/approach: The framework combines mental mapping with exploratory walking. It interweaves…

  15. Initial Clinical Experience With Surgical Technique of Robot-assisted Transperitoneal Laparoscopic Partial Nephrectomy

    Cheng-Kuang Yang


    Conclusion: Robot-assisted LPN is feasible and may be a viable alternative to open or LPN in selected patients with small exophytic renal tumors. Compared with standard LPN, the robotic assisted LPN approach with precise renal reconstruction under a safe warm ischemia time is feasible and can be easily adopted by those with experience in robot-assisted surgery.

  16. Initial tensile test results from J316 stainless steel irradiated in the HFIR spectrally tailored experiment

    Pawel, J.E.; Grossbeck, M.L.; Rowcliffe, A.F. [Oak Ridge National Lab., TN (United States)] [and others


    The objective of this work is to determine the effects of neutron irradiation on the mechanical properties of austenitic stainless steel alloys. In this experiment, the spectrum has been tailored to reduce the thermal neutron flux and achieve a He/dpa level near that expected in a fusion reactor.

  17. Experiences of Student Speech-Language Pathology Clinicians in the Initial Clinical Practicum: A Phenomenological Study

    Nelson, Lori A.


    Speech-language pathology literature is limited in describing the clinical practicum process from the student perspective. Much of the supervision literature in this field focuses on quantitative research and/or the point of view of the supervisor. Understanding the student experience serves to enhance the quality of clinical supervision. Of…

  18. Initial experience with transperitoneal laparoscopic nephrectomy in an Irish hospital setting.

    Forde, J C


    Laparoscopic nephrectomy has gained widespread acceptance as a treatment for both benign and malignant conditions and is becoming increasingly popular in Irish hospitals. We report a single surgeon, single centre experience with 20 consecutive laparoscopic nephrectomies comparing them to 20 open cases performed prior to the establishment of a laparoscopic service.

  19. Initiation of subduction at Atlantic-type margins: Insights from laboratory experiments

    Faccenna, Claudio; Giardini, Domenico; Davy, Philippe; Argentieri, Alessio


    We have performed scaled lithospheric experiments to simulate the behavior of a ocean-continent plate system subjected to compressional strain over a geological timescale. Experiments have been constructed using sand and silicone putty, representing the brittle upper crust and the ductile lower crust/upper mantle, respectively; the layers floated on glucose syrup simulating the asthenosphere. Compressional stress is achieved by displacing a piston at constant velocity perpendicular to the plate margin. We investigate the influence of four parameters: (1) the negative buoyancy of oceanic lithosphere, (2) the horizontal body forces between continent and ocean, and (3) the brittle and (4) the ductile strength of the passive margin. Two numbers express the importance of these parameters: the Argand number (Ar), representing the ratio between the body force of continent and its integrated strength, and the buoyancy number (F), representing the ratio between the buoyancy force of ocean and its ductile resistance. We obtain three scenarios. In experiments with Ar 3 and F 1 the continent collapses toward the ocean, producing back-arc extension and subduction, simulating the post-Alpine Neogene evolution of the Mediterranean area. In experiments with Ar 3 and F > 1 the passive margin slowly evolves toward trench nucleation with the formation of a viscous mantle instability. We conclude that the latter model can be applied to the evolution of Atlantic-type margins, where there is evidence of this ongoing process.

  20. Investigating the Impact of Mediated Learning Experiences on Cooperative Peer Communication during Group Initiatives

    White, Robert; Dinos, Sokratis


    This study investigates how structured Mediated Learning Experiences may improve peer-cooperative communication within problem-solving task exercises. Two groups (n = 22) of Year 8 students (mean age 13 +/- 5 months) were randomly selected to participate in this study. The study began with two one-hour sessions of activity-based problem-solving…

  1. An Experience-Based Learning Framework: Activities for the Initial Development of Sustainability Competencies

    Caniglia, Guido; John, Beatrice; Kohler, Martin; Bellina, Leonie; Wiek, Arnim; Rojas, Christopher; Laubichler, Manfred D.; Lang, Daniel


    Purpose: This paper aims to present an experience-based learning framework that provides a bottom-up, student-centered entrance point for the development of systems thinking, normative and collaborative competencies in sustainability. Design/methodology/approach: The framework combines mental mapping with exploratory walking. It interweaves…

  2. Teachers' Experiences of a Single-Sex Initiative in a Co-Education School

    Gray, Colette; Wilson, Joanne


    Argued to "raise boys' grades" and "boost boys' academic achievement", single-sex classes in coeducation schools is one strategy among a plethora aimed at raising standards. This paper explores the experiences of teachers in one coeducation post-primary school that sought to raise academic performance, particularly among boys, and to improve…

  3. A dual functional fluorescent probe for glioma imaging mediated by blood-brain barrier penetration and glioma cell targeting.

    Ma, Hongwei; Gao, Zhiyong; Yu, Panfeng; Shen, Shun; Liu, Yongmei; Xu, Bainan


    Glioma is a huge threat for human being because it was hard to be completely removed owing to both the infiltrating growth of glioma cells and integrity of blood brain barrier. Thus effectively imaging the glioma cells may pave a way for surgical removing of glioma. In this study, a fluorescent probe, Cy3, was anchored onto the terminal of AS1411, a glioma cell targeting aptamer, and then TGN, a BBB targeting peptide, was conjugated with Cy3-AS1411 through a PEG linker. The production, named AsT, was characterized by gel electrophoresis, (1)H NMR and FTIR. In vitro cellular uptake and glioma spheroid uptake demonstrated the AsT could not only be uptaken by both glioma and endothelial cells, but also penetrate through endothelial cell monolayer and uptake by glioma spheroids. In vivo, AsT could effectively target to glioma with high intensity. In conclusion, AsT could be used as an effective glioma imaging probe.

  4. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

    Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)


    Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

  5. IL-13Ra2- and glioma stem cell-pulsed dendritic cells induce glioma cell death in vitro

    Ying Wang; Ruifan Xie; Hongquan Niu; Ting Lei


    Objective Gliomas are the most common malignant tumors in the central nervous system. Despite mul-tiple therapies including surgery, chemotherapy, and radiotherapy, the prognosis of patients remains poor. Immunotherapy is an alternative method of treating glioma, and the use of dendritic cel vaccines is one of the promising treatment options. However, there is no specific tumor cel antigen that can trigger dendritic cel s (DCs). IL-13Ra2 is a specific antigen expressed in glioma cel s; in the current study, we have at-tempted to explore whether IL-13Ra2 could be the antigen that triggers DCs and to envisage its application as potential therapy for glioma. Methods The expression of IL-13Ra2 was detected in U251 glioma cel lines and primary glioma tissues using dif erent methods. DCs from human blood were isolated and pulsed with recombinant IL-13Ra2, fol-lowing which the cytotoxicity of these DCs on glioma cel s was detected and analyzed. Results About 55.9% human glioma tissue cel s expressed IL-13Ra2, while normal brain tissue cel s did not show any expression. DC vaccines loaded with IL-13Ra2, glioma cel antigen, and brain tumor stem cel (BTSC) antigen could significantly stimulate the proliferation of T lymphocytes and induce cel death in the glioma tissue. Compared to other groups, DC vaccines loaded with BTSC antigen showed the strongest ability to activate cytotoxic T lymphocytes (CTLs), while the glioma cel antigen group showed no significant dif erence. Conclusion IL-13Ra2, which is expressed in gliomas and by glioma stem cel s, as wel as IL-13Ra2 could prove to be potential antigens for DC vaccine-based immunotherapy.

  6. Graduate Medical Education as a Lever for Collaborative Change: One Institution's Experience with a Campuswide Patient Safety Initiative.

    Vath, Richard J; Musso, Mandi W; Rabalais, Lauren S; Dunbar, Alston; Hosea, Stephen; Johnson, Angela C; Bolton, Michael; Rhynes, Vernon K; Caffery, Terrell S; Tynes, L Lee; Mantzor, Savarra; Miller, Bahnsen; Calongne, Laurinda L


    The 2013 closure of a public hospital in Baton Rouge, LA transformed graduate medical education (GME) at Our Lady of the Lake Regional Medical Center (OLOL). Administrators were tasked with incorporating residents into patient safety and quality improvement initiatives to fulfill regulatory obligations. This report outlines our experiences as we built these patient safety and quality improvement initiatives in a rapidly expanding independent academic medical center. We joined the Alliance of Independent Academic Medical Centers (AIAMC) to meet and learn from national peers. To fulfill the scholarly activity requirement of the AIAMC's National Initiative IV, we formed a multidisciplinary team to develop a patient safety education project. Prioritized monthly team meetings allowed for project successes to be celebrated and circulated within the organization. The public-private partnership that more than quadrupled the historic size of GME at OLOL has, in the past 2 years, led to the development of an interdisciplinary team. This team has expanded to accommodate residency program leadership from across the campus. Our National Initiative IV project won a national award and inspired several follow-up initiatives. In addition, this work led to the formation of a Patient Safety and Clinical Quality Improvement fellowship that matched its first fellow in 2015. Through the commitment and support of hospital and medical education leaders, as well as a focus on promoting cultural change through scholarly activity, we were able to greatly expand patient safety and quality improvement efforts in our institution.

  7. Fostering of Less Commonly Taught Language Initiatives — The Minnesota Experience

    Leonard Anthony Polakiewicz


    Full Text Available First, let me express my sincere gratitude to NCOLCTL for awarding me this prestigious recognition bearing the name of a man who was responsible for many important initiatives and contributions relating to the promotion of the interests of LCTLs. Although for the past 36 years I have been teaching Russian and Polish, in my discussion today I will focus mainly on Polish, the less common of my less commonly taught languages. We can view the future of LCTLs in two ways: paraphrasing Anton Chekhov—one is the view that everything passes and nothing matters; the other view is that nothing passes and everything matters. If we are guided by the first outlook in assessing the present and future status of LCTLs we will conclude that despite all of our initiatives to promote and safeguard the interests of LCTLs, in the final analysis developments beyond our control will threaten the survival of LCTLs as part of institutionalized curriculum at many institutions. Thus, all of our efforts will prove to be in vain.

  8. Initial 10-year Experience of Sperm Cryopreservation Services for Cancer Patients

    Hong-Chiang Chang


    Full Text Available Offering sperm cryopreservation to preserve the fertility of male cancer patients is a relatively recent service in Asia. This study analyzed the types of cancer, timing of collection, sperm quality, and utilization for reproductive services by patients during a 10-year period at a medical center in Taiwan. A total of 75 oncology patients elected to freeze sperm for fertility preservation at our medical center during the initial 10 years of the availability of this service. The mean age of the patients was 25.7 years. Storage was discontinued in 13 (17% patients and their survival duration was 13.1 ±11.1 months. The utilization rate of sperm cryo-preservation was 2.8% (75/2642. The types of cancer varied, with leukemia (35%, lymphoma (25%, and testicular cancer (13% comprising the largest groups. A significantly lower sperm count was found in patients with chronic myelogenous leukemia, suggesting the need for earlier sperm collection after initiation of cancer treatment. Only three (4% patients utilized their specimens for reproductive purposes. There was no clinical pregnancy during the study period, although one biochemical pregnancy was achieved. The low rates of sperm cryostorage for fertility preservation in cancer patients in this study suggest that there is a need for greater emphasis of this option for male oncology patients whose fertility is likely to be affected by chemotherapeutic treatment.

  9. The Accelerating Access Initiative: experience with a multinational workplace programme in Africa.

    Van der Borght, S; Janssens, V; Schim van der Loeff, M F; Kajemba, A; Rijckborst, H; Lange, J M A; Rinke de Wit, T F


    A multinational company with operations in several African countries was committed to offer antiretroviral treatment to its employees and their dependants. The Accelerating Access Initiative (AAI), an initiative of six pharmaceutical companies and five United Nations' agencies, offered the possibility of obtaining brand antiretroviral drugs (ARVs) at 10% of the commercial price. PharmAccess, a foundation aimed at removing barriers to AIDS treatment in Africa, helped to establish an HIV policy and treatment guidelines, and a workplace programme was rolled out from September 2001. Private sector employers in Africa are keen to take more responsibility in HIV prevention and AIDS care. An important hurdle for African employers remains the price and availability of ARVs. The programme encountered various hurdles, among them the need for multiple contracts with multiple companies, complex importation procedures, taxes levied on ARVs, lack of support from pharmaceutical companies in importation and transportation, slow delivery of the drugs, lack of institutional memory in pharmaceutical companies and government policies excluding the company from access to ARVs under the AAI. The launch of the AAI enabled this multinational company to offer access to ARVs to its employees and dependants. The private sector should have access to these discounted drugs under the AAI. A network of local AAI offices should be created to assist in logistics of drugs ordering, purchase and clearance. No taxes should be levied on ARVs.

  10. Radiopurity control in the NEXT-100 double beta decay experiment: procedures and initial measurements

    Alvarez, V; Bettini, A; Borges, F I G M; Carcel, S; Castel, J; Catala, J M; Cebrian, S; Cervera, A; Conde, C A N; Dafni, T; Dias, T H V T; Diaz, J; Egorov, M; Esteve, R; Evtoukhovitch, P; Fernandes, L M P; Ferrario, P; Ferreira, A L; Ferrer-Ribas, E; Freitas, E D C; Gehman, V M; Gil, A; Giomataris, I; Goldschmidt, A; Gomez, H; Gomez-Cadenas, J J; Gonzalez, K; Gonzalez-Diaz, D; Gutierrez, R M; Hauptman, J; Morata, J A Hernando; Herrera, D C; Herrero, V; Iguaz, F J; Irastorza, I G; Kalinnikov, V; Labarga, L; Liubarsky, I; Lopes, J A M; Lorca, D; Losada, M; Luzon, G; Mari, A; Martin-Albo, J; Martinez, A; Miller, T; Moiseenko, A; Monrabal, F; Monteiro, C M B; Monzo, J M; Mora, F J; Moutinho, L M; Vidal, J Munoz; da Luz, H Natal; Navarro, G; Nebot, M; Nygren, D; Oliveira, C A B; de Solorzano, A Ortiz; Palma, R; Perez, J; Aparicio, J L Perez; Renner, J; Ripoll, L; Rodriguez, A; Rodriguez, J; Santos, F P; Santos, J M F dos; Segui, L; Serra, L; Shuman, D; Simon, A; Sofka, C; Sorel, M; Toledo, J F; Tomas, A; Torrent, J; Tsamalaidze, Z; Vazquez, D; Velicheva, E; Veloso, J F C A; Villar, J A; Webb, R C; Weber, T; White, J; Yahlali, N


    The Neutrino Experiment with a Xenon TPC (NEXT) is intended to investigate the neutrinoless double beta decay of 136Xe, which requires a severe suppression of potential backgrounds. An extensive screening and material selection process is underway for NEXT since the control of the radiopurity levels of the materials to be used in the experimental set-up is a must for rare event searches. First measurements based on Glow Discharge Mass Spectrometry and gamma-ray spectroscopy using ultra-low background germanium detectors at the Laboratorio Subterr\\'aneo de Canfranc (Spain) are described here. Activity results for natural radioactive chains and other common radionuclides are summarized, being the values obtained for some materials like copper and stainless steel very competitive. The implications of these results for the NEXT experiment are also discussed.

  11. Role of laser myringotomy in a pediatric otolaryngology practice: initial experience

    Shah, Udayan K.


    A new technology (OtoLAM) to fenestrate the tympanic membrane with the carbon dioxide laser (CO2), in the office or the operating room, has been introduced over the last three years. While not new conceptually, this product offers the ability to easily create a precise window into the middle ear using a portable system. Controversy regarding the indications and benefits of this technique, amplified by the costs of the system and the marketing of the technology prior to extensive clinical testing, has plagued the clinical application of this technology. We report our experience over the past year with this system in a busy pediatric otolaryngology practice. Laser fenestration of the tympanic membrane has been useful for the insertion of tympanostomy tubes, and for the minimally invasive evaluation of the middle ear. Our small experience to date reveals that there is a limited role for laser tympanic membrane fenestration in a busy pediatric otolaryngology practice.

  12. Shock initiation behavior of PBXN-9 determined by gas gun experiments

    Sanchez, Nathaniel J [Los Alamos National Laboratory; Gustavsen, Richard L [Los Alamos National Laboratory; Hooks, Daniel E [Los Alamos National Laboratory


    The shock to detonation transition was evaluated in the HMX based explosive PBXN-9 by a series of light-gas gun experiments. PBXN-9 consists of 92 wt% HMX, 2wt% Hycar 4054 & 6 wt% dioctyl adipate with a density of 1.75 g/cm{sup 3} and 0.8% voids. The experiments were designed to understand the specifics of wave evolution and the run distance to detonation as a function of input shock pressure. These experiments were conducted on gas guns in order to vary the input shock pressure accurately. The primary diagnostics were embedded magnetic gauges, which are based on Faraday's law of induction, and Photon Doppler Velocimetry (PDV). The run distance to detonation vs. shock pressure, or 'Pop plot,' was redefined as log(X*) = 2.14-1.82 log(P), which is substantially different than previous data. The Hugoniot was refined as U{sub s} = 2.32 + 2.21 U{sub p}. This data will be useful for the development of predictive models for the safety and performance of PBXN-9 along with providing increased understanding of HMX based explosives in varying formulations.

  13. Metabolomic Screening of Tumor Tissue and Serum in Glioma Patients Reveals Diagnostic and Prognostic Information

    Lina Mörén


    Full Text Available Glioma grading and classification, today based on histological features, is not always easy to interpret and diagnosis partly relies on the personal experience of the neuropathologists. The most important feature of the classification is the aimed correlation between tumor grade and prognosis. However, in the clinical reality, large variations exist in the survival of patients concerning both glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers for a more reliable classification of glioma tumors as well as for prognosis. We analyzed relative metabolite concentrations in serum samples from 96 fasting glioma patients and 81 corresponding tumor samples with different diagnosis (glioblastoma, oligodendroglioma and grade (World Health Organization (WHO grade II, III and IV using gas chromatography-time of flight mass spectrometry (GC-TOFMS. The acquired data was analyzed and evaluated by pattern recognition based on chemometric bioinformatics tools. We detected feature patterns in the metabolomics data in both tumor and serum that distinguished glioblastomas from oligodendrogliomas (ptumor = 2.46 × 10−8, pserum = 1.3 × 10−5 and oligodendroglioma grade II from oligodendroglioma grade III (ptumor = 0.01, pserum = 0.0008. Interestingly, we also found patterns in both tumor and serum with individual metabolite features that were both elevated and decreased in patients that lived long after being diagnosed with glioblastoma compared to those who died shortly after diagnosis (ptumor = 0.006, pserum = 0.004; AUROCCtumor = 0.846 (0.647–1.000, AUROCCserum = 0.958 (0.870–1.000. Metabolic patterns could also distinguish long and short survival in patients diagnosed with oligodendroglioma (ptumor = 0.01, pserum = 0.001; AUROCCtumor = 1 (1.000–1.000, AUROCCserum = 1 (1.000–1.000. In summary, we found different metabolic feature patterns in tumor tissue and serum for glioma diagnosis, grade and survival, which indicates that

  14. Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas


    Childhood Mixed Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

  15. Human glioma growth is controlled by microRNA-10b.

    Gabriely, Galina; Yi, Ming; Narayan, Ravi S; Niers, Johanna M; Wurdinger, Thomas; Imitola, Jaime; Ligon, Keith L; Kesari, Santosh; Esau, Christine; Stephens, Robert M; Tannous, Bakhos A; Krichevsky, Anna M


    MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. ©2011 AACR


    Hirst, Theodore C.; Vesterinen, Hanna M.; Conlin, Samantha; Egan, Kieren J.; Antonic, Ana; McLean, Aaron Lawson; Macleod, Malcolm R.; Whittle, Ian R.; Grant, Robin; Brennan, Paul M.; Sena, Emily S.


    INTRODUCTION: The development of new therapeutics is often characterised by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We set out to test the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in rodent models of glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a 9-point quality checklist. We calculated median survival ratios and used random effects meta-analysis to provide estimates of efficacy. We explored the effects of study design and quality and searched for evidence of publication bias. RESULTS: We found 194 publications using gene therapy in experimental glioma, describing 427 experiments involving 6366 animals. Overall, genetherapy improved median survival by 1.60 fold (95%CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for observed differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity and we observedsimilar findings in a subset of data limited to the most common genetherapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment forglioma. Nevertheless, we have identified areas for improvement in conduct and reporting of such studies. Further work should focus on genes of interest in paradigms that recapitulate human disease. This may improve the translation of such therapies into the clinic.

  17. Tumor Microenvironment and Angiogenic Blood Vessels Dual-Targeting for Enhanced Anti-Glioma Therapy.

    Hu, Quanyin; Kang, Ting; Feng, Jingxian; Zhu, Qianqian; Jiang, Tianze; Yao, Jianhui; Jiang, Xinguo; Chen, Jun


    Advances in active targeting drug delivery system (DDS) have revolutionized glioma diagnosis and therapy. However, the lack of the sufficient targets on glioma cells and limited penetration capability of DDS have significantly compromised the treatment efficacy. In this study, by taking advantages of the abundant extracellular matrix-derived heparan sulfate proteoglycan (HSPG) and enhanced tumor penetration ability mediated by neuropilin-1 (NRP-1) protein, we reported the ATWLPPR and CGKRK peptide dual-decorated nanoparticulate DDS (designated AC-NP) to achieve angiogenic blood vessels and tumor microenvironment dual-targeting effect. The resulted AC-NP displayed the particle size of 123 ± 19.47 nm. Enhanced cellular association of AC-NP was achieved on HUVEC cells and U87MG cells. AC-NP was internalized via caveolin- and lipid raft-mediated mechanism with the involvement of energy and lysosome in HUVEC cells and via caveolin- and lipid raft-mediated pathway with the participation of energy, microtubulin, and lysosome in U87MG cells. After loading with anticancer drug, paclitaxel (PTX), the enhanced apoptosis induction and antiproliferative activity were achieved by AC-NP. Furthermore, in vitro U87MG tumor spheroids assays showed a deeper penetration and an enhanced inhibitory effect against the U87MG tumor spheroids achieved by AC-NP. In vivo animal experiment showed that decoration of AC peptide on the nanoparticulate DDS resulted in extensive accumulation at glioma site and improved anti-glioma efficacy. Collectively, the results suggested that AC-NP holds great promise to serve as an effective tumor blood vessel and tumor microenvironment dual-targeting DDS with enhanced penetration capability, holding great potential in improving anti-glioma efficacy.

  18. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    Shanshan Wang


    Full Text Available Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS. The complexity of glioma, especially the existence of the blood-brain barrier (BBB, makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications.

  19. Slit2/Robo1 signaling in glioma migration and invasion.

    Xu, Yun; Li, Wen-Liang; Fu, Li; Gu, Feng; Ma, Yong-Jie


    Slit2/Robo1 is a conserved ligand-receptor system, which greatly affects the distribution, migration, axon guidance and branching of neuron cells. Slit2 and its transmembrane receptor Robo1 have different distribution patterns in gliomas. The expression of Slit2 is at very low levels in pilocytic astrocytoma, fibrillary astrocytoma and glioblastoma, while Robo1 is highly expressed in different grades of gliomas at both mRNA and protein levels. Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Although the specific mechanisms of tumor-suppressive effect of Slit2/Robo1 have not been elucidated, it has been proved that Slit2/Robo1 signaling inhibits glioma cell migration and invasion by inactivation of Cdc42-GTP. With the research development on the molecular mechanisms of Slit2/Robo1 signaling in glioma invasion and migration, Slit2/Robo1 signaling may become a potential target for glioma prevention and treatment.

  20. Initial experience with optical-CT scanning of RadBall Dosimeters

    Oldham, M; Clift, C; Thomas, A; Farfan, E; Foley, T; Jannik, T; Adamovics, J; Holmes, C; Stanley, S, E-mail: Mark.Oldham@Duke.ed


    The RadBall dosimeter is a novel device for providing 3-D information on the magnitude and distribution of contaminant sources of unknown radiation in a given hot cell, glovebox, or contaminated room. The device is presently under evaluation by the National Nuclear Lab (NNL, UK) and the Savannah River National Laboratory (SRNL, US), for application as a diagnostic device for such unknown contaminants in the nuclear industry. A critical component of the technique is imaging the dose distribution recorded in the RadBall using optical-CT scanning. Here we present our initial investigations using the Duke Mid-sized Optical-CT Scanner (DMOS) to image dose distributions deposited in RadBalls exposed to a variety of radiation treatments.

  1. Antimicrobial Resistance Control Strategies: A Coordinated Research Initiative Experience in the Asia Pacific Region.

    Lapierre, Lisette; Asenjo, Gabriela; Vergara, Constanza; Cornejo, Javiera


    The objective was to gather information on the status of antimicrobial surveillance in the Asia Pacific region and suggest control strategies. Twenty-one economies of the Asia Pacific region participated in this initiative. A survey was conducted on antimicrobial use and surveillance throughout the region. A workshop was carried out to create awareness about the issue and discuss the implementation of control strategies. Based on the survey results and workshop conclusions, it can be established that there is better understanding of the implications of antimicrobial resistance in the human medicine area. Only few economies take actions to control antimicrobial resistance on a veterinary/agricultural level. To confront antimicrobial resistance, it is critical to raise awareness; cooperation between all countries is needed to apply international standards, to be able to have harmonized public policies. Countries must align and improve their systems for surveillance and monitoring of antimicrobial resistance in human, animals, and the environment.

  2. Robotic pulmonary lobectomy for lung cancer treatment: program implementation and initial experience

    Ricardo Mingarini Terra

    Full Text Available ABSTRACT Objective: To describe the implementation of a robotic thoracic surgery program at a public tertiary teaching hospital and to analyze its initial results. Methods: This was a planned interim analysis of a randomized clinical trial aimed at comparing video-assisted thoracoscopic surgery and robotic surgery in terms of the results obtained after pulmonary lobectomy. The robotic surgery program developed at the Instituto do Câncer do Estado de São Paulo, in the city of São Paulo, Brazil, is a multidisciplinary initiative involving various surgical specialties, as well as anesthesiology, nursing, and clinical engineering teams. In this analysis, we evaluated the patients included in the robotic lobectomy arm of the trial during its first three months (from April to June of 2015. Results: Ten patients were included in this analysis. There were eight women and two men. The mean age was 65.1 years. All of the patients presented with peripheral tumors. We performed right upper lobectomy in four patients, right lower lobectomy in four, and left upper lobectomy in two. Surgical time varied considerably (range, 135-435 min. Conversion to open surgery or video-assisted thoracoscopic surgery was not necessary in any of the cases. Intraoperative complications were not found. Only the first patient required postoperative transfer to the ICU. There were no deaths or readmissions within the first 30 days after discharge. The only postoperative complication was chest pain (grade 3, in two patients. Pathological examination revealed complete tumor resection in all cases. Conclusions: When there is integration and proper training of all of the teams involved, the implementation of a robotic thoracic surgery program is feasible and can reduce morbidity and mortality.

  3. Initial Thomson Scattering Survey of Local Helicity Injection and Ohmic Plasmas at the Pegasus Toroidal Experiment

    Schlossberg, D. J.; Bodner, G. M.; Bongard, M. W.; Fonck, R. J.; Winz, G. R.


    A multipoint Thomson scattering diagnostic has recently been installed on the Pegasus ST. The system utilizes a frequency-doubled Nd:YAG laser (λ0 ~ 532 nm), spectrometers with volume phase holographic gratings, and a gated, intensified CCD camera. It provides measurements of Te and ne at 8 spatial locations for each spectrometer once per discharge. A new multiple aperture and beam dump system has been implemented to mitigate interference from stray light. This system has provided initial measurements in the core region of plasmas initiated by local helicity injection (LHI), as well as conventional Ohmic L- and H-mode discharges. Multi-shot averages of low-density (ne ~ 3 ×1018 m-3) , Ip ~ 0 . 1 MA LHI discharges show central Te ~ 75 eV at the end of the helicity injection phase. Ip ~ 0 . 13 MA Ohmic plasmas at moderate densities (ne ~ 2 ×1019 m-3) have core Te ~ 150 eV in L-mode. Generally, these plasmas do not reach transport equilibrium in the short 25 ms pulse length available. After an L-H transition, strong spectral broadening indicates increasing Te, to values above the range of the present spectrometer system with a high-dispersion VPH grating. Near-term system upgrades will focus on deploying a second spectrometer, with a lower-dispersion grating capable of measuring the 0.1-1.0 keV range. The second spectrometer system will also increase the available number of spatial channels, enabling study of H-mode pedestal structure. Work supported by US DOE Grant DE-FG02-96ER54375.

  4. Multi-frequency harmonic arrays: initial experience with a novel transducer concept for nonlinear contrast imaging.

    Forsberg, Flemming; Shi, William T; Jadidian, Bahram; Winder, Alan A


    Nonlinear contrast imaging modes such as second harmonic imaging (HI) and subharmonic imaging (SHI) are increasingly important for clinical applications. However, the performance of currently available transducers for HI and SHI is significantly constrained by their limited bandwidth. To bypass this constraint, a novel transducer concept termed multi-frequency harmonic transducer arrays (MFHA's) has been designed and a preliminary evaluation has been conducted. The MFHA may ultimately be used for broadband contrast enhanced HI and SHI with high dynamic range and consists of three multi-element piezo-composite sub-arrays (A-C) constructed so the center frequencies are 4f(A) = 2f(B) = f(C) (specifically 2.5/5.0/10.0 MHz and 1.75/3.5/7.0 MHz). In principle this enables SHI by transmitting on sub-array C receiving on B and, similarly, from B to A as well as HI by transmitting on A receiving on B and, likewise, from B to C. Initially transmit and receive pressure levels of the arrays were measured with the elements of each sub-array wired in parallel. Following contrast administration, preliminary in vitro HI and SHI signal-to-noise ratios of up to 40 dB were obtained. In conclusion, initial design and in vitro characterization of two MFHA's have been performed. They have an overall broad frequency bandwidth of at least two octaves. Due to the special design of the array assembly, the SNR for HI and SHI was comparable to that of regular B-mode and better than commercially available HI systems. However, further research on multi-element MFHA's is required before their potential for in vivo nonlinear contrast imaging can be assessed.

  5. Promoter hypomethylation regulates CD133 expression in human gliomas

    Kouichi Tabu; Ken Sasai; Taichi Kimura; Lei Wang; Eiko Aoyanagi; Shinji Kohsaka; Mishie Tanino; Hiroshi Nishihara; Shinya Tanaka


    Brain tumor-initiating cells (BTICs) have been enriched using antibodies against the cell surface protein CD133;however,the biological relevance and the regulatory mechanism of CD133 expression in human gliomas are not yet understood.In this study,we initially demonstrated that CD133 was overexpressed in high-grade human glioblastomas where CD133-positive cells were focally observed as a micro-cluster.In addition,CD133 transcripts with exon 1A,1B,or 1C were predominantly expressed in glioblastomas.To elucidate the mechanism regulating this aberrant expression of CD133,three proximal promoters (P1,P2,and P3) containing a CpG island were isolated.In U251MG and T98Gglioblastoma cells,the P1 region flanking exon 1A exhibited the highest activity among the three promoters,and this activity was significantly inactivated by in vitro methylation.After treatment with the demethylating agent 5-azacytidine and/or the histone deacetylase inhibitor valproic acid,the expression level of CD133 mRNA was significantly restored in glioma cells.Importantly,hypomethylation of CpG sites within the P1,P2,and P3 regions was observed by bisulfite sequencing in human glioblastoma tissues with abundant CD133 mRNA.Taken together,our results indicate that DNA hypomethylation is an important determinant of CD133 expression in glioblastomas,and this epigenetic event may be associated with the development of BTICs expressing CD133.

  6. Conceptual design of initial opacity experiments on the national ignition facility

    Heeter, R. F.; Bailey, J. E.; Craxton, R. S.; Devolder, B. G.; Dodd, E. S.; Garcia, E. M.; Huffman, E. J.; Iglesias, C. A.; King, J. A.; Kline, J. L.; Liedahl, D. A.; McKenty, P. W.; Opachich, Y. P.; Rochau, G. A.; Ross, P. W.; Schneider, M. B.; Sherrill, M. E.; Wilson, B. G.; Zhang, R.; Perry, T. S.


    Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative-convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures eV and electron densities 21~\\text{cm}-3$ . The iron will be probed using continuum X-rays emitted in a ps, diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design, of the NIF beams deliver 500 kJ to the mm diameter hohlraum, and the remaining directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.

  7. SU-E-E-05: Initial Experience On Physics Rotation of Radiological Residents

    Zhang, J; Williams, D; DiSantis, D; Hardy, P; Oates, M [University of Kentucky, Lexington, KY (United States)


    Purpose: The new ABR core exam integrates physics into clinical teaching, with an emphasis on understanding image quality, image artifacts, radiation dose and patient safety for each modality and/or sub-specialty. Accordingly, physics training of radiological residents faces a challenge. A traditional teaching of physics through didactic lectures may not fully fulfill this goal. It is also difficult to incorporate physics teaching in clinical practice due to time constraints. A dedicated physics rotation may be a solution. This study is to evaluate a full week physics workshop developed for the first year radiological residents. Methods: The physics rotation took a full week. It included three major parts, introduction lectures, hand-on experiences and observation of technologist operation. An introduction of basic concepts was given to each modality at the beginning. Hand-on experiments were emphasized and took most of time. During hand-on experiments, residents performed radiation measurements, studied the relationship between patient dose and practice (i.e., fluoroscopy), investigated influence of acquisition parameters (i.g., kV, mAs) on image quality, and evaluated image quality using phantoms A physics test before and after the workshop was also given but not for comparison purpose. Results: The evaluation shows that the physics rotation during the first week of residency in radiology is preferred by all residents. The length of a full week of physics workshop is appropriate. All residents think that the intensive workshop can significantly benefit their coming clinical rotations. Residents become more comfortable regarding the use of radiation and counseling relevant questions such as a pregnant patient risk from a CE PE examination. Conclusion: A dedicated physics rotation, assisting with didactic lectures, may fulfill the requirements of physics of the new ABR core exam. It helps radiologists deeply understand the physics concepts and more efficiently use

  8. Initial experience in setting up a medical student first responder scheme in South Central England.

    Seligman, William H; Ganatra, Sameer; England, David; Black, John J M


    Prehospital emergency medicine (PHEM) is a recently recognised subspecialty of emergency medicine, and anaesthetics, intensive care and acute medicine, in the UK, and yet it receives little to no mention in many undergraduate medical curricula. However, there is growing interest in PHEM among medical students and junior doctors. Several programmes are in existence across the UK that serve to provide teaching and exposure of prehospital care to medical students and junior doctors. However, relatively few students are able to gain significant first-hand experience of treating patients in the prehospital phase. In this short report, we discuss our experience of launching the student first responder (SFR) scheme across three counties in the Thames Valley. Medical students are trained by the regional ambulance service and respond to life-threatening medical emergencies in an ambulance response vehicle. The scheme is likely to benefit the ambulance service by providing a wider pool of trained volunteer first responders able to attend to emergency calls, to benefit patients by providing a quick response at their time of need, and to benefit medical students by providing first-hand experience of medical emergencies in the community. In its first 15 months of operation, SFRs were dispatched to 343 incidents. This scheme can serve as a training model for other ambulance services and medical schools across the UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  9. Initial Results from the Radiation Dosimetry Experiment (RaD-X) Balloon Flight Mission

    Mertens, Christopher J.


    The NASA Radiation Dosimetry Experiment (RaD-X) high-altitude balloon mission was successfully launched from Fort Sumner, New Mexico USA on 25 September, 2015. Over 15 hours of science data were obtained from four dosimeters at altitudes above about 25 km. The four dosimeters flown on the RaD-X science payload are a Hawk version 3.0 Tissue Equivalent Proportional Counter (TEPC) manufactured by Far West Technologies, a Liulin dosimeter-spectrometer produced by the Solar Research and Technology Institute, Bulgarian Academy of Sciences, a total ionizing dose detector manufactured by Teledyne Microelectronic Technologies, and the RaySure detector provided by the University of Surrey.

  10. [Initial experiences with the new environmental medicine course in graduate education].

    Nemitz, B


    The "master of environmental medicine" is a new medical subspeciality in Germany. Specialised physicians can qualify for it, if they have spent at least an additional period of 1.5 years at a recognized institution in the field. Furthermore the attendance of a 200 hours comprehensive specialist's training course is required. Preliminary experience with this comprehensive course, as offered by our institution (Academy of Occupational and Environmental Medicine, Berlin, Germany) is lined out. Additionally, details of the curriculum, which was specifically designed for this purpose by our institution, are given. The results of an evaluation-procedure (questionnaire) among those participants, who completed the first parts of the course, are discussed.

  11. Strain localization and evolving kinematic efficiency of initiating strike-slip faults within wet kaolin experiments

    Hatem, Alexandra E.; Cooke, Michele L.; Toeneboehn, Kevin


    Using wet kaolin experiments, we document the evolution of strain localization during strike-slip fault maturation under variable boundary conditions (pre-existing fault, depth of and distribution of basal shear). While the nature of the basal shear influences strain localization observed at the clay surface, similarities between experiments reveal a general conceptual model of strain accommodation. First, shear strain is accommodated as distributed shear (Stage 0), then by development of echelon faults (Stage I), then by interaction, lengthening and propagation of those echelon faults (Stage II) and, finally, by slip along through-going fault (Stage III). Stage II serves as a transitory period when the system reorganizes after sufficient strain localization. Here, active fault system complexity is maximized as faults link producing apparent rotation of active fault surfaces without material rotation. As the shear zone narrows, off-fault deformation decreases while fault slip and kinematic efficiency increases. We quantify kinematic efficiency as the ratio of fault slip to applied displacement. All fault systems reach a steady-state efficiency in excess of 80%. Despite reducing off-fault deformation, the through-going fault maintains <1.5 cm structural irregularities (i.e., stepovers), which suggests that small (<3 km) stepovers may persist along mature, efficient faults in the crust.

  12. Application of Radar Reflectivity Factor in Initializing Cloud-Resolving Mesoscale Model. Part Ⅱ: Numerical Simulation Experiments

    LIU Hongya; XU Haiming; XUE Jishan; HU Zhijin; SHEN Tongli


    Microphysics elements and vertical velocity retrieved were incorporated using the nudging method into the initial data assimilation of GRAPES (Global/Regional Assimilation and Prediction System) model.Simulation experiments indicated that nudging technique was effective in forcing the model forecast gradually consistent to the observations, yielding the thermodynamically and dynamically balanced analysis field. As viewed from the simulation results, water vapor is vital to precipitation, and it is a governing factor for the amount and duration of precipitation. The initial cloud water, rain water, and vertical velocity determine the strength distribution of convection and precipitation at the beginning time of forecast; the horizontal wind field steers the motion of the mesoscale weather system embedded in and impacts the position of precipitation zone to a large extent. The simulation experiments show that the influence of the initial retrieval data on prediction weakens with the increase of forecast time, and within the first hour of forecast, the retrieval data have an important impact on the evolution of the weather system, but its influence becomes trivial after the first three hours. Changing the nudging coefficient and the integral time-spacing of numerical model will bring some influences to the results. Herein only one radar reflectivity was used, the radar observations did not cover the whole model domain, and some empirical parameters were used in the retrieval method, therefore some differences still lie between simulation and observation to a certain extent, and further studies on several aspects are expected.

  13. Combined laparoscopic and thoracoscopic Ivor Lewis esophagectomy for esophageal cancer: initial experience from China

    LI Hui; HU Bin; YOU Bin; MIAO Jin-bai; FU Yi-li; CHEN Qi-rui


    Background Minimally invasive lvor Lewis esophagectomy was usually performed with either hand-sewn or circular stapler anastomosis through a small thoracotomy or using a side-to-side stapler anastomotic technique.This study aimed to present our initial results of lvor Lewis esophagectomy using a circular-stapled anastomosis with transoral anvil technique.Methods Six patients with esophageal cancer underwent minimally invasive lvor Lewis esophagectomy with an intrathoracic circular-stapled end-to-end anastomosis.The abdominal portion was operated on laparoscopically,and the thoracic portion was done using thoracoscopic techniques.A 25 mm anvil connected to a 90 cm long delivery tube was introduced transorally to the esophageal stump in a tilted position,the anvil head was then connected to circular stapler.The anastomosis was completed under direct thoracoscopic view.Results A total of six patients in this report successfully underwent total laparoscopic and thoracoscopic lvor Lewis esophagectomy with a circular-stapled anastomosis using a transoral anvil.They were five male and one female patients,and had a mean age of 55 years (range,38-69 years).The thoracic and abdominal operations were successfully performed without any intraoperative complications or conversion to laparotomy or thoracotomy.The passage of the anvil head was technically easy and successful in all six cases.The mean overall operative time was (260±42) minutes (range,220-300 minutes),and the mean estimated blood loss was (520±160) ml (range,130-800 ml).Patients resumed a liquid oral diet on postoperative day seven.The median length of hospital stay was 17 days (range,9-25 days).The postoperative pathological diagnosis was esophageal squamous cell carcinoma in five patients and esophageal small cell carcinoma in one patient.Tumors were staged as T2N0M0 in three cases,T2N1M0 in one case,and T3N0M0 in two cases.During the mean follow-up of 2.5 months (range,2-4months),there were no intraoperative

  14. Intent at day case laparoscopic cholecystectomy in Owerri, Nigeria: Initial experiences

    Christopher Nonso Ekwunife


    Full Text Available Background and Objective: Laparoscopic cholecystectomy has been the default operation for cholelithiasis at Federal Medical Centre, Owerri for the past 2 years and the outcomes have been good. The duration of post operative stay has been decreasing. We therefore initiated a preliminary 2-year prospective study in May 2010 to determine the feasibility of carrying out day case laparoscopic cholecystectomy in our hospital. Materials and Methods: Patients undergoing laparoscopic cholecystectomy were included in the study if they satisfied the following criteria: Age < 65 years, body mass index < 35 kg/m 2 , American Society of Anaesthesiology physical status class I and II, patient residence within 20 km radius of the hospital, patient acceptance of the procedure and absence of previous complicated upper abdominal surgery. Results: Twelve patients (10 females, 2 males were worked up with the intent of achieving same-day discharge of the patients. Five of the patients (41.7% were discharged on the day of operation. The reasons for overnight stay included inadequate pain control, insertion of drain and patient wishes. There was no conversion to open surgery, no major complications and no case of readmission to the hospital. Conclusions: Day case laparoscopic cholecystectomy in our environment could be safely promoted but will depend on improved facilities and patient enlightenment.

  15. Local Control of Perivascular Malignant Liver Lesions Using Percutaneous Irreversible Electroporation: Initial Experiences

    Eller, Achim, E-mail:; Schmid, Axel, E-mail: [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Radiology (Germany); Schmidt, Joachim, E-mail: [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Anesthesiology (Germany); May, Matthias, E-mail:; Brand, Michael, E-mail:; Saake, Marc, E-mail:; Uder, Michael, E-mail:; Lell, Michael, E-mail: [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Radiology (Germany)


    PurposeThis study was designed to assess efficacy and safety in the treatment of perivascular malignant liver lesions using percutaneous, computed tomography (CT)-guided irreversible electroporation (IRE).MethodsFourteen patients (mean age 58 ± 11 years) with 18 malignant liver lesions were consecutively enrolled in this study. IRE was performed in patients not eligible for surgery and lesions abutting large vessels or bile ducts. Follow-up exams were performed using multislice-CT (MS-CT) or MRI.ResultsMedium lesion diameter was 20 ± 5 mm. Ten of 14 (71 %) were successfully treated with no local recurrence to date (mean follow-up 388 ± 160 days). One case left initial tumor control unclear and additional RFA was performed 4 weeks after IRE. Complications occurred in 4 of 14 (29 %) cases. In one case, intervention was terminated and abdominal bleeding required laparotomy. In two cases, a postinterventional hematothorax required intervention. In another case, abdominal bleeding could be managed conservatively. No complications related to the bile ducts occurred.ConclusionsPercutaneous IRE seems to be effective in perivascular lesions but is associated with a higher complication rate compared with thermoablative techniques.

  16. [Telecommunication--a medium for improving prenatal diagnosis and gynecologic ultrasound diagnosis? Initial experiences].

    Sohn, C; Beldermann, F; Wallwiener, D; Lepold, H; Bastert, G


    To establish the requirements for real-time transfer of an ultrasound examination via telecommunication network the following tests were performed: The ultrasound data were transferred from the video out of an ultrasound system to a basis terminal of the German Telekom. Simultaneously, an external video camera filmed the positioning and movements of the ultrasound transducer, and the verbal comments were recorded. These informations were transmitted to Karlsruhe and London, where they were rerouted to the examination room in Heidelberg. Here the informations were received on a Telecom reception unit/terminal and compared directly with the initial signal. The quality was sufficient if the moving ultrasound images and the camera image of the transducer as well as the oral comment were transmitted over 2 parallel ISDN lines. The delay to a real-time transmission of the examination process is only in the range of milliseconds. If only one ISDN line is used, the image quality is unsatisfactory, three parallel lines do not bring significant improvement of image quality. Telemedicine seems a new possibility to bring the knowledge of specialized centers to the practicing gynaecologists thus avoiding unnecessary referrals. Still unanswered, however, are the problem of liability, data protection and costs.

  17. Initial operating experience of the 12-MW La Ola photovoltaic system.

    Ellis, Abraham; Lenox, Carl (SunPower Corporation, Richmond, CA); Johnson, Jay; Quiroz, Jimmy Edward; Schenkman, Benjamin L.


    The 1.2-MW La Ola photovoltaic (PV) power plant in Lanai, Hawaii, has been in operation since December 2009. The host system is a small island microgrid with peak load of 5 MW. Simulations conducted as part of the interconnection study concluded that unmitigated PV output ramps had the potential to negatively affect system frequency. Based on that study, the PV system was initially allowed to operate with output power limited to 50% of nameplate to reduce the potential for frequency instability due to PV variability. Based on the analysis of historical voltage, frequency, and power output data at 50% output level, the PV system has not significantly affected grid performance. However, it should be noted that the impact of PV variability on active and reactive power output of the nearby diesel generators was not evaluated. In summer 2011, an energy storage system was installed to counteract high ramp rates and allow the PV system to operate at rated output. The energy storage system was not fully operational at the time this report was written; therefore, analysis results do not address system performance with the battery system in place.

  18. Can we reduce the burden of depression? The Australian experience with beyondblue: the national depression initiative.

    Hickie, Ian


    Throughout the Asia Pacific region, there is an urgent need to reduce the burden of depression by increasing depression awareness, reducing stigma and dismantling those social barriers that prevent full participation by people with depression. This paper describes the development and early achievements of the Australian depression initiative, beyondblue. A review of the key priorities of beyondblue and their impacts during the first three years of operation (2001-03). Key achievements include: the degree of national recognition of beyondblue; size and scope of media impact; growth in website utilisation; increased reporting of the community's recognition of people with depression; genuine reforms in life insurance and income protection; development of a new national consumer and carer organisation; establishment of major population-based preventative and early intervention programs; system-wide reform of primary care-based mental health services; national educational program uptake by general practitioners; and, development of key awareness and intervention programs for use in schools and the workplace. In its first three years of operation, beyondblue has had a major impact on depression awareness in Australia and demonstrable gains have been made in reducing stigma and major social barriers. A pre-existing national mental health policy and implementation plan, a substantial funding base and participation by key political, media and community leaders have been essential elements of its short-term success. Its longer-term impact will now depend on more sustainable community and business partnerships as well as the growth of a more influential consumer and carer voice.

  19. Intraoperative perfusion contrast echocardiography. Initial experience during coronary artery bypass grafting.

    Kabas, J S; Kisslo, J; Flick, C L; Johnson, S H; Craig, D M; Stanley, T E; Smith, P K


    Intraoperative evaluation of the effectiveness of myocardial revascularization has been limited by an inability to assess regional myocardial perfusion. Microbubbles of sonicated diatrizoate sodium and diatrizoate meglumine (Renografin) have been an effective echocardiographic contrast agent and have been employed clinically during cardiac catheterization. This recent development in contrast-enhanced two-dimensional echocardiography permits real-time imaging of transmural myocardial blood flow but has not been evaluated in the operating room. This study represents the initial surgical application of this directed technique and was designed to evaluate the safety and efficacy of intraoperative perfusion contrast echocardiography in assessing the results of coronary artery bypass grafting. Twenty men with significant coronary artery disease ranging in age from 49 to 73 years were studied. Direct contrast agent injection into completed saphenous vein bypass grafts caused the myocardium supplied by each graft to be well delineated and provided a tomographic view of contrast distribution. The enhanced region was well correlated with the size and distribution of the native vessel. Rapid contrast washout (less than 20 seconds) indicated satisfactory regional perfusion. Contrast echocardiography prolonged the operation less than 10 minutes and did not result in any perioperative complications.

  20. Participation in ICZM initiatives: critical aspects and lessons learnt from the Mediterranean and Black Sea experiences.

    Soriani, Stefano; Buono, Fabrizia; Tonino, Marco; Camuffo, Monica


    Public participation is recognized as a necessary tool to ensure a successful implementation of Integrated Coastal Zone Management (ICZM) strategies and plans. This paper, based on the experiences carried out in the Mediterranean and in the Black Sea within the EU FP7 project PEGASO, presents some critical aspects and lessons learnt regarding participation in ICZM projects. The research shows that data availability, the complexity of data interpretation, an inadequate legal and cultural framework and the difficulties in promoting integration of all the components of coastal management within short term projects are all elements that if not properly considered since the beginning of the participatory process may hinder public participation effectiveness. Moreover the definition of the spatial scale of coastal phenomenon as well as the discrepancy between the local scale of coastal governance and the complex multi-scale nature of coastal systems remain highly critical aspects to be addressed.


    Mærsk-Møller, Hans Martin; Jørgensen, Bo Nørregaard


    papers and collective results on Software Product Line Engineering (SPLE) in the context of small teams. This paper remedies this situation by providing experiences from a successful approach of applying software product line engineering in a small team. We conduct a transition from single......-system production to Software Product Line (SPL) in the domain of greenhouse climate control systems. The domain contains inherent variabilities and extensive commonalities between the products in scope, which makes it a prime candidate for SPLE - besides having good business prospects. The transitioning to SPLE...... an existing methodology, PuLSETM, drew advantages of NetBeans Rich Client Platform, and based the product line on the existing application....

  2. Significance of assessment experiences during initial teacher training in physical education

    Wagner dos Santos


    Full Text Available Abstract This study investigates how students in the final semester of their teacher training program (licensure at the Center of Physical Education and Sports (CEFD, Espírito Santo Federal University, Brazil, (reinterpret their assessment experiences, an integral component of their teacher training. It employs the narrative as a theoretical and methodological perspective, and it utilizes student portfolios, as well as focus groups and semi-structured individual interviews as inputs for data generation. Ten students in their eighth, or final, semester participated in this study. These were the total respondents to a "call for volunteers" among the 2014 graduating class. The results suggest that the students believe the assessment processes of their teaching practices in physical education are disjointed. They feel that the disciplines that allow them to review their own performance during teacher training are more efficient and play a stronger role in their education.

  3. Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil

    Fábio Sândoli de Brito Jr


    Full Text Available Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial. The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment.

  4. Experimental warming delays autumn senescence in a boreal spruce bog: Initial results from the SPRUCE experiment

    Richardson, Andrew; Furze, Morgan; Aubrecht, Donald; Milliman, Thomas; Nettles, Robert; Krassovski, Misha; Hanson, Paul


    Phenology is considered one of the most robust indicators of the biological impacts of global change. In temperate and boreal regions, long-term data show that rising temperatures are advancing spring onset (e.g. budburst and flowering) and delaying autumn senescence (e.g. leaf coloration and leaf fall) in a wide range of ecosystems. While warm and cold temperatures, day length and insolation, precipitation and water availability, and other factors, have all been shown to influence plant phenology, the future response of phenology to rising temperatures and elevated CO2 still remains highly uncertain because of the challenges associated with conducting realistic manipulative experiments to simulate future environmental conditions. At the SPRUCE (Spruce and Peatland Responses Under Climatic and Environmental Change) experiment in the north-central United States, experimental temperature (0 to +9° C above ambient) and CO2 (ambient and elevated) treatments are being applied to mature, and intact, Picea mariana-Sphagnum spp. bog communities in their native habitat through the use of ten large (approximately 12 m wide, 10 m high) open-topped enclosures. We are tracking vegetation green-up and senescence in these chambers, at both the individual and whole-community level, using repeat digital photography. Within each chamber, digital camera images are recorded every 30 minutes and uploaded to the PhenoCam ( project web page, where they are displayed in near-real-time. Image processing is conducted nightly to extract quantitative measures of canopy color, which we characterize using Gcc, the green chromatic coordinate. Data from a camera mounted outside the chambers (since November 2014) indicate strong seasonal variation in Gcc for both evergreen shrubs and trees. Shrub Gcc rises steeply in May and June, and declines steeply in September and October. By comparison, tree Gcc rises gradually from March through June, and declines gradually from

  5. Simple electrical model and initial experiments for intra-body communications.

    Gao, Y M; Pun, S H; Du, M; Mak, P U; Vai, M I


    Intra-Body Communication(IBC) is a short range "wireless" communication technique appeared in recent years. This technique relies on the conductive property of human tissue to transmit the electric signal among human body. This is beneficial for devices networking and sensors among human body, and especially suitable for wearable sensors, telemedicine system and home health care system as in general the data rates of physiologic parameters are low. In this article, galvanic coupling type IBC application on human limb was investigated in both its mathematical model and related experiments. The experimental results showed that the proposed mathematical model was capable in describing the galvanic coupling type IBC under low frequency. Additionally, the calculated result and experimental result also indicated that the electric signal induced by the transmitters of IBC can penetrate deep into human muscle and thus, provide an evident that IBC is capable of acting as networking technique for implantable devices.

  6. UNIX trademark in high energy physics: What we can learn from the initial experiences at Fermilab

    Butler, J.N.


    The reasons why Fermilab decided to support the UNIX operating system are reviewed and placed in the content of an overall model for high energy physics data analysis. The strengths and deficiencies of the UNIX environment for high energy physics are discussed. Fermilab's early experience in dealing with a an open'' multivendor environment, both for computers and for peripherals, is described. The human resources required to fully exploit the opportunities are clearly growing. The possibility of keeping the development and support efforts within reasonable bounds may depend on our ability to collaborate or at least to share information even more effectively than we have in the past. 7 refs., 4 figs., 5 tabs.

  7. Hepatobilio-pancreatic robotic surgery: initial experience from a single center institute.

    Quijano, Yolanda; Vicente, Emilio; Ielpo, Benedetto; Duran, Hipolito; Diaz, Eduardo; Fabra, Isabel; Malave, Luis; Ferri, Valentina; Plaza, Carlos; Lindemann, Jan Lammel; D'Andrea, Vito; Caruso, Riccardo


    The use of robotic surgery in the hepatobilio-pancreatic (HBP) field is still limited. Our aim is to present our early experience of robotic liver resection. A retrospective review of robotic pancreatic and liver resection was performed at Sanchinarro University hospital from October 2010 to April 2016. Since the beginning of the robotic program in our center, 22 hepatic procedures and 45 pancreatic robotic procedures have been performed. Of the 21 patients subjected to liver resection, 13 (65%) were for malignancy. There were two left hepatectomies, one right hepatectomy, one associated liver partition and portal vein ligation staged procedure (both steps by robotic approach), three bisegmentectomies and three segmentectomies, eight wedge resections, and three pericystectomies. The mean operating time was 282 min. The overall conversion rate and postoperative complication rate were 4.7 and 19%, respectively. The mean length of hospital stay was 13.4 days (range 4-64 days). Of the 45 patients subjected to pancreatic resection, 22 were male and 23 female. The average age of all patients was 62 years (range 31-82 years). The mean operating room (OR) time was 370 min (120-780 min). Among the procedures performed were 15 pancreatico-duodenectomies, 19 distal pancreatectomies, and 11 enucleations. All procedures in the HBP area were R0. Our early experience shows that robotic surgery is a safe and feasible procedure in the HBP area. The complication and mortality rates are comparable to those of open surgery, but with the advantages of minimally invasive surgery.

  8. Assessment of Initial Test Conditions for Experiments to Assess Irradiation Assisted Stress Corrosion Cracking Mechanisms

    Busby, Jeremy T [ORNL; Gussev, Maxim N [ORNL


    Irradiation-assisted stress corrosion cracking is a key materials degradation issue in today s nuclear power reactor fleet and affects critical structural components within the reactor core. The effects of increased exposure to irradiation, stress, and/or coolant can substantially increase susceptibility to stress-corrosion cracking of austenitic steels in high-temperature water environments. . Despite 30 years of experience, the underlying mechanisms of IASCC are unknown. Extended service conditions will increase the exposure to irradiation, stress, and corrosive environment for all core internal components. The objective of this effort within the Light Water Reactor Sustainability program is to evaluate the response and mechanisms of IASCC in austenitic stainless steels with single variable experiments. A series of high-value irradiated specimens has been acquired from the past international research programs, providing a valuable opportunity to examine the mechanisms of IASCC. This batch of irradiated specimens has been received and inventoried. In addition, visual examination and sample cleaning has been completed. Microhardness testing has been performed on these specimens. All samples show evidence of hardening, as expected, although the degree of hardening has saturated and no trend with dose is observed. Further, the change in hardening can be converted to changes in mechanical properties. The calculated yield stress is consistent with previous data from light water reactor conditions. In addition, some evidence of changes in deformation mode was identified via examination of the microhardness indents. This analysis may provide further insights into the deformation mode under larger scale tests. Finally, swelling analysis was performed using immersion density methods. Most alloys showed some evidence of swelling, consistent with the expected trends for this class of alloy. The Hf-doped alloy showed densification rather than swelling. This observation may be

  9. Endoscopic endonasal skull base approach for parasellar lesions: Initial experiences, results, efficacy, and complications

    Shigetoshi Yano


    Full Text Available Background: Endoscopic surgery is suitable for the transsphenoidal approach; it is minimally invasive and provides a well-lit operative field. The endoscopic skull base approach through the large opening of the sphenoid sinus through both nostrils has extended the surgical indication for various skull base lesions. In this study, we describe the efficacy and complications associated with the endoscopic skull base approach for extra- or intradural parasellar lesions based on our experiences. Methods: Seventy-four cases were treated by an endoscopic skull base approach. The indications for these procedures included 55 anterior extended approaches, 10 clival approaches, and 9 cavernous approaches. The operations were performed through both the nostrils using a rigid endoscope. After tumor removal, the skull base was reconstructed by a multilayered method using a polyglactin acid (PGA sheet. Results: Gross total resection was achieved in 82% of pituitary adenomas, 68.8% of meningiomas, and 60% of craniopharyngiomas in anterior extended approach and in 83.3% of chordomas in clival approach, but only in 50% of the tumors in cavernous approach. Tumor consistency, adhesion, and/or extension were significant limitations. Visual function improvements were achieved in 37 of 41 (90.2% cases. Cerebrospinal fluid (CSF leakage (9.5%, infections (5.4%, neural injuries (4.1%, and vascular injuries (2.7% were the major complications. Conclusions: Our experiences show that the endoscopic skull base approach is a safe and effective procedure for various parasellar lesions. Selection of patients who are unlikely to develop complications seems to be an important factor for procedure efficacy and good outcome.

  10. Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing

    Bruno Monteiro Tavares Pereira

    Full Text Available CONTEXT AND OBJECTIVE: Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. DESIGN AND SETTING: Retrospective study at Universidade Estadual de Campinas. METHODS: Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. RESULTS: A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3 teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7, or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22% and 21% of the total calls. CONCLUSION: Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

  11. Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing.

    Pereira, Bruno Monteiro Tavares; Calderan, Thiago Rodrigues Araújo; Silva, Marcos Tadeu Nolasco da; Silva, Antonio Carlos da; Marttos, Antonio Carlos; Fraga, Gustavo Pereira


    Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. Retrospective study at Universidade Estadual de Campinas. Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3) teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7), or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22% and 21% of the total calls. Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

  12. Health-related quality of life in stable, long-term survivors of low-grade glioma

    F.W. Boele; L. Douw; J.C. Reijneveld; R. Robben; M.J.B. Taphoorn; N.K. Aaronson; J.J. Heimans; M. Klein


    Purpose: Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoa

  13. Health-related quality of life in stable, long-term survivors of low-grade glioma

    Boele, F.W.; Douw, L.; Reijneveld, J.C.; Robben, R.; Taphoorn, M.J.B.; Aaronson, N.K.; Heimans, J.J.; Klein, M.


    Purpose: Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or

  14. Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma : a prospective longitudinal study

    Froklage, F E; Oosterbaan, L J; Sizoo, E M; de Groot, M; Bosma, I; Sanchez, E; Douw, L; Heimans, J J; Reijneveld, J C; Lagerwaard, F J; Buter, J; Uitdehaag, B M J; Klein, M; Postma, T J


    Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally,

  15. The Role of Model and Initial Condition Error in Numerical Weather Forecasting Investigated with an Observing System Simulation Experiment

    Prive, Nikki C.; Errico, Ronald M.


    A series of experiments that explore the roles of model and initial condition error in numerical weather prediction are performed using an observing system simulation experiment (OSSE) framework developed at the National Aeronautics and Space Administration Global Modeling and Assimilation Office (NASA/GMAO). The use of an OSSE allows the analysis and forecast errors to be explicitly calculated, and different hypothetical observing networks can be tested with ease. In these experiments, both a full global OSSE framework and an 'identical twin' OSSE setup are utilized to compare the behavior of the data assimilation system and evolution of forecast skill with and without model error. The initial condition error is manipulated by varying the distribution and quality of the observing network and the magnitude of observation errors. The results show that model error has a strong impact on both the quality of the analysis field and the evolution of forecast skill, including both systematic and unsystematic model error components. With a realistic observing network, the analysis state retains a significant quantity of error due to systematic model error. If errors of the analysis state are minimized, model error acts to rapidly degrade forecast skill during the first 24-48 hours of forward integration. In the presence of model error, the impact of observation errors on forecast skill is small, but in the absence of model error, observation errors cause a substantial degradation of the skill of medium range forecasts.

  16. Visual exploratory analysis of integrated chromosome 19 proteomic data derived from glioma cancer stem-cell lines based on novel nonlinear dimensional data reduction techniques

    Lespinats, Sylvain; Pinker-Domenig, Katja; Meyer-Bäse, Uwe; Meyer-Bäse, Anke


    Chromosome 19 is known to be linked to neurodegeneration and many cancers. Glioma-derived cancer stem cells (GSCs) are tumor-initiating cells and may be refractory to radiation and chemotherapy and thus have important implications for tumor biology and therapeutics. The analysis and interpretation of large proteomic data sets requires the development of new data mining and visualization approaches. Traditional techniques are insufficient to interpret and visualize these resulting experimental data. The emphasis of this paper lies in the presentation of novel approaches for the visualization, clustering and projection representation to unveil hidden data structures relevant for the accurate interpretation of biological experiments. These qualitative and quantitative methods are applied to the proteomic analysis of data sets derived from the GSCs. The achieved clustering and visualization results provide a more detailed insight into the expression patterns for chromosome 19 proteins.

  17. Initial Surgical Experience with Aortic Valve Repair: Clinical and Echocardiographic Results

    da Costa, Francisco Diniz Affonso; Colatusso, Daniele de Fátima Fornazari; da Costa, Ana Claudia Brenner Affonso; Balbi Filho, Eduardo Mendel; Cavicchioli, Vinicius Nesi; Lopes, Sergio Augusto Veiga; Ferreira, Andrea Dumsch de Aragon; Collatusso, Claudinei


    Introduction Due to late complications associated with the use of conventional prosthetic heart valves, several centers have advocated aortic valve repair and/or valve sparing aortic root replacement for patients with aortic valve insufficiency, in order to enhance late survival and minimize adverse postoperative events. Methods From March/2012 thru March 2015, 37 patients consecutively underwent conservative operations of the aortic valve and/or aortic root. Mean age was 48±16 years and 81% were males. The aortic valve was bicuspid in 54% and tricuspid in the remaining. All were operated with the aid of intraoperative transesophageal echocardiography. Surgical techniques consisted of replacing the aortic root with a Dacron graft whenever it was dilated or aneurysmatic, using either the remodeling or the reimplantation technique, besides correcting leaflet prolapse when present. Patients were sequentially evaluated with clinical and echocardiographic studies and mean follow-up time was 16±5 months. Results Thirty-day mortality was 2.7%. In addition there were two late deaths, with late survival being 85% (CI 95% - 68%-95%) at two years. Two patients were reoperated due to primary structural valve failure. Freedom from reoperation or from primary structural valve failure was 90% (CI 95% - 66%-97%) and 91% (CI 95% - 69%-97%) at 2 years, respectively. During clinical follow-up up to 3 years, there were no cases of thromboembolism, hemorrhage or endocarditis. Conclusions Although this represents an initial series, these data demonstrates that aortic valve repair and/or valve sparing aortic root surgery can be performed with satisfactory immediate and short-term results. PMID:27556321

  18. Reflectance confocal microscopy-guided laser ablation of basal cell carcinomas: initial clinical experience.

    Sierra, Heidy; Yélamos, Oriol; Cordova, Miguel; Chen, Chih-Shan Jason; Rajadhyaksha, Milind


    Laser ablation offers a procedure for precise, fast, and minimally invasive removal of superficial and early nodular basal cell carcinomas (BCCs). However, the lack of histopathological confirmation has been a limitation toward widespread use in the clinic. A reflectance confocal microscopy (RCM) imaging-guided approach offers cellular-level histopathology-like feedback directly on the patient, which may then guide and help improve the efficacy of the ablation procedure. Following an ex vivo benchtop study (reported in our earlier papers), we performed an initial study on 44 BCCs on 21 patients in vivo, using a pulsed erbium:ytterbium aluminum garnet laser and a contrast agent (aluminum chloride). In 10 lesions on six patients, the RCM imaging-guided detection of either presence of residual tumor or complete clearance was immediately confirmed with histopathology. Additionally, 34 BCCs on 15 patients were treated with RCM imaging-guided laser ablation, with immediate confirmation for clearance of tumor (no histopathology), followed by longer-term monitoring, currently in progress, with follow-up imaging (again, no histopathology) at 3, 6, and 18 months. Thus far, the imaging resolution appears to be sufficient and consistent for monitoring efficacy of ablation in the wound, both immediately postablation and subsequently during recovery. The efficacy results appear to be promising, with observed clearance in 19 cases of 22 cases with follow-ups ranging from 6 to 21 months. An additional 12 cases with 1 to 3 months of follow-ups has shown clearance of tumor but a longer follow-up time is required to establish conclusive results. Further instrumentation development will be necessary to cover larger areas with a more automatically controlled instrument for more uniform, faster, and deeper imaging of margins. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  19. Initial clinical experience with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO).

    Tuan, J; Vischioni, B; Fossati, P; Srivastava, A; Vitolo, V; Iannalfi, A; Fiore, M R; Krengli, M; Mizoe, J E; Orecchia, R


    We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35-37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21-74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70-74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy.

  20. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience

    Jian Zhou; Yi-Feng He; Yu-Qi Wang; Zhao-You Tang; Jia Fan; Zheng Wang; Zhi-Quan Wu; Shuang-Jian Qiu; Xiao-Wu Huang; Yao Yu; Jian Sun; Yong-Sheng Xiao


    AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune(R), rapamycin) in a consecutive cohort of 248 liver allograft recipients.METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT.RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT.Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable.CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

  1. Conceptual design of initial opacity experiments on the national ignition facility

    Heeter, R.  F.; Bailey, J.  E.; Craxton, R.  S.; DeVolder, B.  G.; Dodd, E.  S.; Garcia, E.  M.; Huffman, E.  J.; Iglesias, C.  A.; King, J.  A.; Kline, J.  L.; Liedahl, D.  A.; McKenty, P.  W.; Opachich, Y.  P.; Rochau, G.  A.; Ross, P.  W.; Schneider, M.  B.; Sherrill, M.  E.; Wilson, B.  G.; Zhang, R.; Perry, T.  S.


    Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures${\\geqslant}150$ eV and electron densities${\\geqslant}7\\times 10^{21}~\\text{cm}^{-3}$. The iron will be probed using continuum X-rays emitted in a${\\sim}200$ ps,${\\sim}200~\\unicode[STIX]{x03BC}\\text{m}$diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design

  2. Challenges in Drug Discovery for Neurofibromatosis Type 1-Associated Low-Grade Glioma

    Cora Antoinette Ricker


    Full Text Available Neurofibromatosis type 1 (NF1 is an autosomal dominant disorder that results from germline mutations of the NF1 gene, creating a predisposition to low-grade gliomas (pilocytic astrocytoma; PA in young children. Insufficient data and resources represent major challenges to identifying the best possible drug therapies for children with this tumor. Herein, we summarize the currently-available cell lines, genetically-engineered mouse models, and therapeutic targets for these low-grade gliomas (LGGs. Conspicuously absent are human tumor-derived cell lines or patient-derived xenograft models for NF1-LGG. New collaborative initiatives between patients and their families, research groups and pharmaceutical companies are needed to create transformative resources and broaden the knowledge base relevant to identifying cooperating genetic drivers and possible drug therapeutics for this common pediatric brain tumor.

  3. Initial experience in 115 patients with the retrievable Cook Celect vena cava filter.

    Doody, O; Given, M F; Kavnoudias, H; Street, M; Thomson, K R; Lyon, S M


    The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14-267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78-211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14-267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow-up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

  4. [A new balloon-expandable plastic endoprosthesis. Initial report of experience with the malleable thermostent].

    Beck, A


    A new system of balloon-expandable stents for different purposes is presented. A special plastic material that can be shaped by a hot balloon technique or other internal or external heating modalities has been developed. The plastic material - a distant derivative of polyurethane - is caprolactone, which is soft from 52 degrees C to 70 degrees C. Using balloon techniques, the "thermo-stent" can be modeled to suit the form of the vessels, the bile ducts or the bronchial tree, as required. The balloon can be heated simply by means of a warm NaCl solution, electric matter in the balloon itself or microwaves. The plastic material can even be heated directly, which is especially beneficial if the stent needs to be thicker, e.g. in the bronchial tree, by an electric network within the plastic material, which heats the material to the necessary temperature by electric current. When the balloon is cooled after the dilatation the new form, the plastic has been modeled to is maintained exactly. The advantages of this thermo-stent will be the perfect adaptation to every individual situation in the intraluminal vessels, the bile ducts, and even the bronchi. The problems encountered hitherto with conventional metallic stents, e.g. high thrombogenicity, risk of metal intoxication or metallic rupture of filaments, have not be seen so far in animal experiments.

  5. Initial SAM Calibration Gas Experiments on Mars: Quadrupole Mass Spectrometer Results and Implications

    Franz, Heather B.; Trainer, Melissa G.; Malespin, Charles A.; Mahaffy, Paul R.; Atreya, Sushil K.; Becker, Richard H,; Benna, Mehdi; Conrad, Pamela G.; Eigenbrode, Jennifer L.; Freissinet, Caroline; hide


    The Sample Analysis at Mars (SAM) instrument suite of the Mars Science Laboratory (MSL) Curiosity rover is equipped to analyze both martian atmospheric gases and volatiles released by pyrolysis of solid surface materials, with target measurements including chemical and isotopic composition (Mahaffy et al., 2012). To facilitate assessment of instrument performance and validation of results obtained on Mars, SAM houses a calibration cell containing CO2, Ar, N2, Xe, and several fluorinated hydrocarbon compounds (Franz et al., 2014; Mahaffy et al., 2012). This report describes the first two experiments utilizing this calibration cell on Mars and gives results from analysis of data acquired with the SAM Quadrupole Mass Spectrometer (QMS). These data support the accuracy of isotope ratios obtained with the QMS (Conrad et al., 2016; Mahaffy et al., 2013) and provide ground-truth for reassessment of analytical constants required for atmospheric measurements, which were reported in previous contributions (Franz et al., 2015, 2014). The most significant implication of the QMS data involves reinterpretation of pre-launch contamination previously believed to affect only CO abundance measurements (Franz et al., 2015) to affect N2 abundances, as well. The corresponding adjustment to the N2 calibration constant presented here brings the atmospheric volume mixing ratios for Ar and N2 retrieved by SAM into closer agreement with those reported by the Viking mission (Owen et al., 1977; Oyama and Berdahl, 1977).

  6. Use of natural user interfaces for image navigation during laparoscopic surgery: initial experience.

    Sánchez-Margallo, Francisco M; Sánchez-Margallo, Juan A; Moyano-Cuevas, José L; Pérez, Eva María; Maestre, Juan


    Surgical environments require special aseptic conditions for direct interaction with the preoperative images. We aim to test the feasibility of using a set of gesture control sensors combined with voice control to interact in a sterile manner with preoperative information and an integrated operating room (OR) during laparoscopic surgery. Two hepatectomies and two partial nephrectomies were performed by three experienced surgeons in a porcine model. The Kinect, Leap Motion, and MYO armband in combination with voice control were used as natural user interfaces (NUIs). After surgery, surgeons completed a questionnaire about their experience. Surgeons required <10 min training with each NUI. They stated that NUIs improved the access to preoperative patient information and kept them more focused on the surgical site. The Kinect system was reported as the most physically demanding NUI and the MYO armband in combination with voice commands as the most intuitive and accurate. The need to release one of the laparoscopic instruments in order to use the NUIs was identified as the main limitation. The presented NUIs are feasible to directly interact in a more intuitive and sterile manner with the preoperative images and the integrated OR functionalities during laparoscopic surgery.

  7. Initial SAM calibration gas experiments on Mars: Quadrupole mass spectrometer results and implications

    Franz, Heather B.; Trainer, Melissa G.; Malespin, Charles A.; Mahaffy, Paul R.; Atreya, Sushil K.; Becker, Richard H.; Benna, Mehdi; Conrad, Pamela G.; Eigenbrode, Jennifer L.; Freissinet, Caroline; Manning, Heidi L. K.; Prats, Benito D.; Raaen, Eric; Wong, Michael H.


    The Sample Analysis at Mars (SAM) instrument suite of the Mars Science Laboratory (MSL) Curiosity rover is equipped to analyze both martian atmospheric gases and volatiles released by pyrolysis of solid surface materials, with target measurements including chemical and isotopic composition (Mahaffy et al., 2012). To facilitate assessment of instrument performance and validation of results obtained on Mars, SAM houses a calibration cell containing CO2, Ar, N2, Xe, and several fluorinated hydrocarbon compounds (Franz et al., 2014; Mahaffy et al., 2012). This report describes the first two experiments utilizing this calibration cell on Mars and gives results from analysis of data acquired with the SAM Quadrupole Mass Spectrometer (QMS). These data support the accuracy of isotope ratios obtained with the QMS (Conrad et al., 2016; Mahaffy et al., 2013) and provide ground-truth for reassessment of analytical constants required for atmospheric measurements, which were reported in previous contributions (Franz et al., 2015, 2014). The most significant implication of the QMS data involves reinterpretation of pre-launch contamination previously believed to affect only CO abundance measurements (Franz et al., 2015) to affect N2 abundances, as well. The corresponding adjustment to the N2 calibration constant presented here brings the atmospheric volume mixing ratios for Ar and N2 retrieved by SAM into closer agreement with those reported by the Viking mission (Owen et al., 1977; Oyama and Berdahl, 1977).

  8. Initial experience with a group presentation of study results to research participants

    Bent Stephen


    Full Text Available Abstract Background Despite ethical imperatives, informing research participants about the results of the studies in which they take part is not often performed. This is due, in part, to the costs and burdens of communicating with each participant after publication of the results. Methods Following the closeout and publication of a randomized clinical trial of saw palmetto for treatment of symptoms of benign prostatic hyperplasia, patients were invited back to the research center to participate in a group presentation of the study results. Results Approximately 10% of participants attended one of two presentation sessions. Reaction to the experience of the group presentation was very positive among the attendees. Conclusion A group presentation to research participants is an efficient method of communicating study results to those who desire to be informed and was highly valued by those who attended. Prospectively planning for such presentations and greater scheduling flexibility may result in higher attendance rates. Trial Registration Number #NCT00037154

  9. Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression.

    Xiao, Jinsong; Liu, Li; Zhong, Zian; Xiao, Cheng; Zhang, Junjian


    Mangiferin, a flavonoid extracted from the leaves of the Anacardiaceae plant, the mango tree, has physiological activity and pharmacological effects in many aspects. The present study aimed to clarify the effect of mangiferin on proliferation and apoptosis of glioma cells and the mechanism of these curative effects of mangiferin. In this experiment, we detected the proliferation using 3-(4,5-dimethylthylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Then, cell apoptosis of U87 glioma cells was measured with the Annexin V-FITC/propidium iodide (PI) apoptosis detection kit, DAPI staining assay and the caspase-3 and caspase-9 activity assay kit. Next, quantitative real-time PCR and gelatin zymography were used to analyze the expression of microRNA-15b (miR-15b) and matrix metalloproteinase-9 (MMP-9), respectively. MMP-9 agonist, miR-15b mimics and anti-miR-15b mimics were added to the U87 glioma cells for elucidating the mechanisms involved in the curative effects of mangiferin. In the present study, mangiferin notably restrained the proliferation and increased the apoptosis of the U87 glioma cells. Meanwhile, mangiferin specifically promoted the expression of miR-15b and suppressed the level of MMP-9 in the U87 glioma cells. miR-15b regulated the expression of MMP-9 in the U87 glioma cells. MMP-9 agonist and anti-miR‑15b reduced the curative effects of mangiferin in the U87 glioma cells. In summary, mangiferin regulates proliferation and apoptosis in glioma cells by induction of miR-15b and inhibition of MMP-9 expression.

  10. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

    Christian Hendrich


    Full Text Available The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications For this purpose, the clinical-radiological progress of a total of 101 patients with various bone healing disturbances was documented (surveillance study. The study included 37 necrosis of the head of the femur, 32 avascular necroses/bone marrow edema of other localization, 12 non-unions, 20 other defects. The application of BMAC was performed in the presence of osteonecrosis via a local injection as part of a core decompression (n=72 or by the local adsorption of intra-operative cellular bone substitution material (scaffold incubated with BMAC during osteosynthesis (n=17 or in further surgery (n=12. After an average of 14 months (2-24 months, the patients were re-examined clinically and radiologically and interviewed. Further surgery was necessary in 2 patients within the follow-up period. These were due to a progression of a collapsed head of the femur with initial necrosis in ARCO Stage III, as well as inadequate new bone formation with secondary loss of correction after periprosthetic femoral fracture. The latter healed after repeated osteosynthesis plus BMAC application without any consequences. Other than these 2 patients, no further complications were observed. In particular, no infections, no excessive new bone formation, no induction of

  11. Establishing a health demographic surveillance site in Bhaktapur district, Nepal: initial experiences and findings

    Aryal Umesh


    Full Text Available Abstract Background A health demographic surveillance system (HDSS provides longitudinal data regarding health and demography in countries with coverage error and poor quality data on vital registration systems due to lack of public awareness, inadequate legal basis and limited use of data in health planning. The health system in Nepal, a low-income country, does not focus primarily on health registration, and does not conduct regular health data collection. This study aimed to initiate and establish the first HDSS in Nepal. Results We conducted a baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The study surveyed 2,712 households comprising a total population of 13,669. The sex ratio in the study area was 101 males per 100 females and the average household size was 5. The crude birth and death rates were 9.7 and 3.9/1,000 population/year, respectively. About 11% of births occurred at home, and we found no mortality in infants and children less than 5 years of age. Various health problems were found commonly and some of them include respiratory problems (41.9%; headache, vertigo and dizziness (16.7%; bone and joint pain (14.4%; gastrointestinal problems (13.9%; heart disease, including hypertension (8.8%; accidents and injuries (2.9%; and diabetes mellitus (2.6%. The prevalence of non-communicable disease (NCD was 4.3% (95% CI: 3.83; 4.86 among individuals older than 30 years. Age-adjusted odds ratios showed that risk factors, such as sex, ethnic group, occupation and education, associated with NCD. Conclusion Our baseline survey demonstrated that it is possible to collect accurate and reliable data in a village setting in Nepal, and this study successfully established an HDSS site. We determined that both maternal and child health are better in the surveillance site compared to the entire country. Risk factors associated with NCDs dominated morbidity and mortality patterns.

  12. Extracorporeal Shock-wave Lithotripsy Success Rate and Complications: Initial Experience at Sultan Qaboos University Hospital

    Mohammed S. Al-Marhoon


    Full Text Available Objective: To assess the efficacy and safety of extracorporeal shock wave lithotripsy with Modularis Vario Siemens in the management of patients with renal and ureteral stones.Methods: Between 2007 and 2009, 225 outpatients were treated with Siemens Modularis Vario lithotripter at Sultan Qaboos University Hospital. Stone size, location, total number of shockwaves, stone-free rate, complications and adjunctive interventions were investigated. Chi-Square and Logistic Regression analyses were used, with p<0.05 set as the level of significance.Results: Of the 225 initial consecutive patients who underwent extracorporeal shock wave lithotripsy, 192 (85% had renal stones and 33 (15% had ureteric stones. The mean±SD stone size was 11.3 ± 4.5 mm, while the mean age of the patients was 39.9 ± 12.8 years with 68.5% males. The mean renal stone size was 11.6 ± 4.7 mm; a mean of 1.3 sessions was required. The mean ureteric stone size was 9.9 ± 3 mm; and a mean of 1.3 sessions was required. Treatment success (defined as complete clearance of ureteric stones, stone-free or clinically insignificant residual fragments of <4 mm for renal stones was 74% for renal stones and 88% for ureteric stones. Additional extracorporeal shock wave lithotripsy and ureteroscopy were the most adjunctive procedures used for stone clearance. Complications occurred in 74 patients (38.5% with renal stones and 13 patients (39.4% with uretetric stones. The most common complication was loin pain (experienced by 16.7% with renal stones and 21% with ureteric stones. Severe renal colic mandating admission occurred in 2% of patients with renal stones and 6% of patients with ureteric stones. In patients with renal stone, steinstrasse occurred in 3.6% and infection post extracorporeal shock wave lithotripsy in 0.5%. Using Multivariate Logistic Regression analysis, factors found to have significant effect on complete stone clearance were serum creatinine (p=0.004 and the number of

  13. Documentation of polio eradication initiative best practices: Experience from WHO African Region.

    Okeibunor, Joseph; Nshimirimana, Deo; Nsubuga, Peter; Mutabaruka, Evariste; Tapsoba, Leonard; Ghali, Emmanuel; Kabir, Shaikh Humayun; Gassasira, Alex; Mihigo, Richard; Mkanda, Pascal


    The African Region is set to achieving polio eradication. During the years of operations, the Polio Eradication Initiative [PEI] in the Region mobilized and trained tremendous amount of manpower with specializations in surveillance, social mobilization, supplementary immunization activities [SIAs], data management and laboratory staff. Systems were put in place to accelerate the eradication of polio in the Region. Standardized, real-time surveillance and response capacity were established. Many innovations were developed and applied to reaching people in difficult and security challenged terrains. All of these resulted in accumulation of lessons and best practices, which can be used in other priority public health intervention if documented. The World Health Organization Regional Office for Africa [WHO/AFRO] developed a process for the documentation of these best practices, which was pretested in Uganda. The process entailed assessment of three critical elements [effectiveness, efficiency and relevance] five aspects [ethical soundness, sustainability, involvement of partners, community involvement, and political commitment] of best practices. A scored card which graded the elements and aspects on a scale of 0-10 was developed and a true best practice should score >50 points. Independent public health experts documented polio best practices in eight countries in the Region, using this process. The documentation adopted the cross-sectional design in the generation of data, which combined three analytical designs, namely surveys, qualitative inquiry and case studies. For the selection of countries, country responses to earlier questionnaire on best practices were screened for potential best practices. Another criterion used was the level of PEI investment in the countries. A total of 82 best practices grouped into ten thematic areas were documented. There was a correlation between the health system performances with DPT3 as proxy, level of PEI investment in countries

  14. Activity of lysosomal exoglycosidases in human gliomas.

    Wielgat, P; Walczuk, U; Szajda, S; Bień, M; Zimnoch, L; Mariak, Z; Zwierz, K


    There is a lot of data suggesting that modifications of cell glycoconjugates may be important in progression of cancer. In the present work we studied activities of lysosomal exoglycosidases: beta-hexosaminidase and its isoenzymes A and B, beta-galactosidase and alpha-mannosidase, in human gliomas. Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from p-nitrophenyl-derivative of appropriate sugars. The activities of the exoglycosidases tested were significantly higher in malignant glial tumors than in control tissue (normal brain tissue) and non-glial tumors. The highest activities of exoglycosidases were observed in high-grade gliomas, and a positive correlation of enzyme activities and degree of malignancy was noted. Our results suggest that lysosomal exoglycosidases may participate in the progression and dynamical development of glial tumors.

  15. Kidney Transplantation From Brain-Dead Donors: Initial Experience in China.

    Li, Y; Li, J; Fu, Q; Chen, L; Fei, J; Deng, S; Qiu, J; Chen, G; Huang, G; Wang, C


    Experience with kidney transplantation from brain-dead donors remains limited in China. Our objective was to evaluate the outcomes of kidney transplantation from brain-dead donors (group 1), compared with those from living ones of the same age (group 2). Clinical data of kidney transplantation from brain-dead donors and living donors in the same age range (18-45 years) performed between May 2007 and December 2011 were analyzed retrospectively. Recipients were analyzed for posttransplantation serum creatinine, creatinine clearance (calculated by the Cockcroft-Gault formula), the number of acute rejection episodes and delayed graft function, and patient/graft survival. Mean donor age was comparable between the 2 groups (31.9 ± 6.5 vs 32.8 ± 7.0 years; P = .268). The terminal serum creatinine level of donors was 125.5 ± 63.5 μmol/L in group 1 (n = 30) and 65.1 ± 13.7 μmol/L in group 2 (n = 110; P = .000). Recipient creatinine clearance was comparable between the 2 groups 1 month posttransplantation and thereafter. Acute rejection episodes were seen in 7 cases in recipients of group 1 (15.9%) and in 15 cases in recipients of group 2 (13.6%; P = .716). The incidence of delayed graft function was higher in recipients of group 1 (18.2%) than that of group 2 (3.6%; P = .002). The 1-, 3-, and 5-year patient/graft survival rate was comparable between the 2 groups. Our study demonstrated kidney transplantation from brain-dead donors achieved acceptable graft function and patient/graft survival in the 5-year follow-up, encouraging the use of this approach. Copyright © 2016. Published by Elsevier Inc.

  16. Initial Clinical Experience: Symmetric-Tip Dialysis Catheter with Helical Flow Characteristics Improves Patient Outcomes.

    Clark, Timothy W I; Redmond, Jonas W; Mantell, Mark P; Nadolski, Gregory J; Mondschein, Jeffrey I; Dowd, Michael F; Dagli, Mandeep S; Sudheendra, Deepak; Shlansky-Goldberg, Richard D; Cohen, Raphael D


    To report preliminary clinical experience with a new symmetric-tip dialysis catheter compared with a conventional split-tip catheter. Over a 5-month period, patients requiring a tunneled catheter for hemodialysis or undergoing exchange of a dysfunctional dialysis catheter at a tertiary academic medical center were retrospectively analyzed. Patients underwent placement of a VectorFlow or Ash Split Cath catheter at the discretion of the inserting interventional radiologist. Patient demographics, catheter patency, mean blood flow rate, and arterial and venous pressures were compared according to catheter type. Catheter failure was analyzed based on clinical and anatomic variables by using a multivariate Cox proportional-hazards model. A total of 33 VectorFlow and 46 Ash Split Cath catheters were placed. Patients in the VectorFlow group had significantly higher body mass index (P = .013) and Charlson Comorbidity Index (P = .049), as well as more non-internal jugular vein placements. At 120 days, 89% of VectorFlow catheters remained functional, compared with 45% of Ash Split Cath catheters (P = .046). The VectorFlow catheter was associated with 16% lower arterial pressures during dialysis (P = .009); mean blood flow rate was equivalent. On multivariate analysis, the risk of catheter failure was 13.3 times higher in the Ash Split Cath group compared with the VectorFlow group (P = .004). Left-sided catheters were also predictive of catheter failure (relative risk = 5.5; P = .02). The VectorFlow catheter was associated with a significant increase in intervention-free catheter patency compared with the Ash Split Cath catheter, with equivalent flow at lower arterial pressures during dialysis. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  17. Digital storytelling and teacher education: an experience in initial teacher training

    Marco Lazzari


    Full Text Available A group of pre-service teachers experienced the digital storytelling as part of their e-learning duties. We describe the structure of the project-work carried out by the students and discuss the results of a questionnaire they filled out after the end of the course, aiming to gather their opinions. The students claim to have enjoyed the proposal and most of them are likely to repeat it in their school, either by developing digital stories themselves or by involving their future students as designers and developers. By questionnaire and interviews with the participants, it is clear that the development experience has changed their attitude towards educational technology, enhanced their digital skills, and increased their self-esteem.Digital storytelling nella formazione iniziale degli insegnanti: un’esperienza nel Tirocinio Formativo AttivoUn gruppo di aspiranti insegnanti iscritti al Tirocinio Formativo Attivo ha affrontato un’esperienza di digital storytelling come parte dei compiti di didattica a distanza. Viene qui descritta la struttura del lavoro svolto dai corsisti e si riflette sui risultati di un questionario sottoposto al termine del corso per rilevarne le opinioni. I corsisti dichiarano di aver gradito la proposta e buona parte di loro ritiene probabile ripeterla a scuola, anche coinvolgendo gli studenti nel progetto e nella realizzazione di narrazioni digitali multimediali. Da questionario e colloqui con i corsisti si deduce che l’esperienza di sviluppo ha mutato il loro atteggiamento verso le tecnologie didattiche, aumentato la loro efficacia come comunicatori digitali e accresciuto la loro autostima.

  18. Robotic-assisted modified retroauricular cervical approach: initial experience in Latin America.

    Chulam, Thiago Celestino; Lira, Renan Bezerra; Kowalski, Luiz Paulo


    to evaluate the thickness of the gastric wall at the time of intra gastric balloon (IGB) placement, at the time of its withdrawal and one month after withdrawal. fifteen morbidly obese patients underwent the introduction of IGB under general anesthesia. In all patients, there was infusion of 500ml of distilled water in the balloon for the test. Measurements of the thickness of the gastric wall were made in the antrum, body and proximal body, using a radial echoendoscope with a frequency of 12MHz and maximum zoom, and its own balloon inflated with 5ml of distilled water. the presence of IGB led to increased wall thickness of the gastric body by expanding the muscle layer. These changes were apparently transient, since 30 days after the balloon withdrawal there was a tendency to return of the wall thickness values ​​observed before the balloon insertion. the use of intragastric balloon for the treatment of obesity determines transient increase in the wall thickness of the gastric body caused by expanded muscle layer. A preocupação com a melhoria dos resultados estéticos e funcionais sem comprometimento dos resultados oncológicos na cirurgia de cabeça e pescoço tem aumentado significativamente. Os procedimentos minimamente invasivos e principalmente aqueles que utilizam a tecnologia robótica permitiram o desenvolvimento de novas abordagens, incluindo o acesso retroauricular, que agora é usado rotineiramente, especialmente na Coréia do Sul. A presente nota irá ilustrar a técnica e a experiência inicial na América Latina, demonstrando que esta abordagem é viável, segura e eficaz oncologicamente, podendo ser utilizada em casos selecionados com um benefício estético evidente.

  19. Initial experience of treating anal fistula with the Surgisis anal fistula plug.

    Chan, S; McCullough, J; Schizas, A; Vasas, P; Engledow, A; Windsor, A; Williams, A; Cohen, C R


    Complex anal fistulas remain a challenge for the colorectal surgeon. The anal fistula plug has been developed as a simple treatment for fistula-in-ano. We present and evaluate our experience with the Surgisis anal fistula plug from two centres. Data were prospectively collected and analysed from consecutive patients undergoing insertion of a fistula plug between January 2007 and October 2009. Fistula plugs were inserted according to a standard protocol. Data collected included patient demographics, fistula characteristics and postoperative outcome. Forty-four patients underwent insertion of 62 plugs (27 males, mean age 45.6 years), 25 of whom had prior fistula surgery. Mean follow-up was 10.5 months Twenty-two patients (50%) had successful healing following the insertion of plug with an overall success rate of 23 out of 62 plugs inserted (35%). Nineteen out of 29 patients healed following first-time plug placement, whereas repeated plug placement was successful in 3 out of 15 patients (20%; p = 0.0097). There was a statistically significant difference in the healing rate between patients who had one or less operations prior to plug insertion (i.e. simple fistulas) compared with patients who needed multiple operations (18 out of 24 patients vs. 4 out of 20 patients; p = 0.0007). Success of treatment with the Surgisis anal fistula plug relies on the eradication of sepsis prior to plug placement. Plugs inserted into simple tracts have a higher success rate, and recurrent insertion of plugs following previous plug failure is less likely to be successful. We suggest the fistula plug should remain a first-line treatment for primary surgery and simple tracts.

  20. Musical hallucinations following insular glioma resection.

    Isolan, Gustavo Rassier; Bianchin, Marino Muxfeldt; Bragatti, José Augusto; Torres, Carolina; Schwartsmann, Gilberto


    Hallucinations can be auditory, visual, tactile, gustatory, or olfactory, and can be caused by psychiatric (such as schizophrenia and depression), neurological (such as cerebrovascular accidents, neoplasia, and infection), or endocrine and metabolic disorders. Musical hallucinations related to neurological disorders are rare. The authors present a case of a patient with a right insular glioma who developed transient musical hallucinations after microsurgical resection of the tumor.

  1. Targeting the bHLH transcriptional networks by mutated E proteins in experimental glioma.

    Beyeler, Sarah; Joly, Sandrine; Fries, Michel; Obermair, Franz-Josef; Burn, Felice; Mehmood, Rashid; Tabatabai, Ghazaleh; Raineteau, Olivier


    Glioblastomas (GB) are aggressive primary brain tumors. Helix-loop-helix (HLH, ID proteins) and basic HLH (bHLH, e.g., Olig2) proteins are transcription factors that regulate stem cell proliferation and differentiation throughout development and into adulthood. Their convergence on many oncogenic signaling pathways combined with the observation that their overexpression in GB correlates with poor clinical outcome identifies these transcription factors as promising therapeutic targets. Important dimerization partners of HLH/bHLH proteins are E proteins that are necessary for nuclear translocation and DNA binding. Here, we overexpressed a wild type or a dominant negative form of E47 (dnE47) that lacks its nuclear localization signal thus preventing nuclear translocation of bHLH proteins in long-term glioma cell lines and in glioma-initiating cell lines and analyzed the effects in vitro and in vivo. While overexpression of E47 was sufficient to induce apoptosis in absence of bHLH proteins, dnE47 was necessary to prevent nuclear translocation of Olig2 and to achieve similar proapoptotic responses. Transcriptional analyses revealed downregulation of the antiapoptotic gene BCL2L1 and the proproliferative gene CDC25A as underlying mechanisms. Overexpression of dnE47 in glioma-initiating cell lines with high HLH and bHLH protein levels reduced sphere formation capacities and expression levels of Nestin, BCL2L1, and CDC25A. Finally, the in vivo induction of dnE47 expression in established xenografts prolonged survival. In conclusion, our data introduce a novel approach to jointly neutralize HLH and bHLH transcriptional networks activities, and identify these transcription factors as potential targets in glioma.

  2. Simpatectomia cervicotoracica por videotoracoscopia: experiência inicial Thoracoscopic cervicodorsal sympathectomy: initial results

    Paulo Kauffman


    Full Text Available O objetivo do presente trabalho é avaliar os resultados iniciais obtidos com a simpatectomia cervicotorácica videotoracoscópica. De outubro de 1995 a outubro de 1997 foram realizados 24 procedimentos em 14 pacientes: dez homens e quatro mulheres, com idades que variaram de 16 a 56 anos, média de 30 anos. Indicações para a operação foram: hiperidrose palmar em dez pacientes, isquemia de mão em três e causalgia em um. Nos casos de hiperidrose, a ressecção da cadeia simpática incluiu T2 e T3. Nos portadores de isquemia e causalgia também o gânglio estrelado foi ressecado. Vinte e três das 24 extremidades mostraram excelente resposta imediata à simpatectomia. Somente uma extremidade de paciente com hiperidrose permaneceu inalterada devido a procedimento incompleto, tendo sido desnervada pela mesma técnica em reoperação posterior, com bom resultado. Pneumotórax residual pós-operatório ocorreu em uma paciente com resolução espontânea. Treze pacientes tiveram seguimento que variou de dois a 18 meses, com média de 11 meses. Não houve mortalidade nessa série, e a principal complicação tardia observada nos pacientes operados por hiperidrose foi a hiperidrose compensatória, que ocorreu, em grau variado, nos nove pacientes com seguimento, sendo que em 30% deles esta manifestação foi significativa. Concluímos tratar-se de procedimento simples, seguro, eficiente e de melhor aceitação por parte dos pacientes do que a operação convencional.This report analyzes the initial results of thoracoscopic cervicodorsal sympathectomy. From October 1995 to October 1997, 24 procedures were accomplished in 14 patients. Ten were males and four were females ranging in age from 16 to 56 (mean 30. Surgical indications were: palmar hyperhidrosis in ten, ischemia of the hand in three and causalgia in one. Resection of the sympathetic chain in hyperhidrosis included T2 and T3. In those with ischemia and causalgia the stellate ganglion was

  3. Motion-Corrected Real-Time Cine Magnetic Resonance Imaging of the Heart: Initial Clinical Experience.

    Rahsepar, Amir Ali; Saybasili, Haris; Ghasemiesfe, Ahmadreza; Dolan, Ryan S; Shehata, Monda L; Botelho, Marcos P; Markl, Michael; Spottiswoode, Bruce; Collins, Jeremy D; Carr, James C


    Free-breathing real-time (RT) imaging can be used in patients with difficulty in breath-holding; however, RT cine imaging typically experiences poor image quality compared with segmented cine imaging because of low resolution. Here, we validate a novel unsupervised motion-corrected (MOCO) reconstruction technique for free-breathing RT cardiac images, called MOCO-RT. Motion-corrected RT uses elastic image registration to generate a single heartbeat of high-quality data from a free-breathing RT acquisition. Segmented balanced steady-state free precession (bSSFP) cine images and free-breathing RT images (Cartesian, TGRAPPA factor 4) were acquired with the same spatial/temporal resolution in 40 patients using clinical 1.5 T magnetic resonance scanners. The respiratory cycle was estimated using the reconstructed RT images, and nonrigid unsupervised motion correction was applied to eliminate breathing motion. Conventional segmented RT and MOCO-RT single-heartbeat cine images were analyzed to evaluate left ventricular (LV) function and volume measurements. Two radiologists scored images for overall image quality, artifact, noise, and wall motion abnormalities. Intraclass correlation coefficient was used to assess the reliability of MOCO-RT measurement. Intraclass correlation coefficient showed excellent reliability (intraclass correlation coefficient ≥ 0.95) of MOCO-RT with segmented cine in measuring LV function, mass, and volume. Comparison of the qualitative ratings indicated comparable image quality for MOCO-RT (4.80 ± 0.35) with segmented cine (4.45 ± 0.88, P = 0.215) and significantly higher than conventional RT techniques (3.51 ± 0.41, P cine (1.51 ± 0.90, P = 0.088 and 1.23 ± 0.45, P = 0.182) were not different. Wall motion abnormality ratings were comparable among different techniques (P = 0.96). The MOCO-RT technique can be used to process conventional free-breathing RT cine images and provides comparable quantitative assessment of LV function and volume

  4. [Initial clinical experience with deep sclerectomy in ambulatory surgery in glaucoma].

    Pitrová, S; Pesková, H; Lesták, J


    Deep sclerectomy is a non-perforating filtering operation used in surgical treatment of open angle glaucomas. The advantage of the operation is the creation of gradual filtration due to the thin trabecular Descement membrane which reduces markedly the risk of development of postoperative complications typical for perforating antiglaucomatous operations. The authors operated at the out-patient department 10 eyes of 8 patients (age 46-81 years). Indications for deep sclerectomy was seven times primary open angle glaucoma (POAG), once capsular glaucoma and twice normotensive glaucoma (NTG). In all eyes deep sclerectomy was indicated because of decompensation of the intraocular pressure with maximum tolerated therapy before surgery. None of the eyes were operated previously. The mean value of intraocular pressure before surgery was 25.1 +/- 6.5 mm Hg. From the results ensues that in nine operated eyes the intraocular pressure at the end of the 6-month follow-up period was compensated without supplementary therapy, only in one eye beta-blockers were prescribed one month after surgery. The cause of failure of filtration was the development of superficial adherence at the site of microperforatiion of the trabecular Descemet membrane which developed during operation. The mean intraocular pressure values at the end of the investigation period were 14.3 +/- 2.8 mm Hg. In two eyes haemorrhage into the anterior chamber was observed on the first day after surgery, the blood was absorbed within 24 hours. Hypotonia in two eyes was only transient and was not associated with a change in the depth of the anterior chamber or other complications. In none of the patients a decline of visual acuity was observed. In three operated eyes a change of refraction was necessary due to discontinuation of miotics after surgery. Deep sclerectomy is a delicate microsurgical technique which calls for experience and skill of the surgeon. The most complicated task is to prevent perforation of the

  5. Single-port video-assisted thoracic surgery for early lung cancer: initial experience in Japan

    Takeuchi, Shingo; Usuda, Jitsuo


    Background Single-port video-assisted thoracic surgery (SPVATS) emerged several years ago as a new, minimally invasive surgery for diseases in the field of respiratory surgery, and is increasingly becoming a subject of interest for some thoracic surgeons in Europe and Asia. However, the adoption rate of this procedure in the United States and Japan remains low. We herein reviewed our experience of SPVATS for early lung cancer in our center, and evaluated the safety and minimal invasiveness of this technique. Methods We retrospectively analyzed patients who had undergone SPVATS for pathological stage I lung cancer in Nippon Medical School Chiba Hokusoh Hospital between September 2012 and October 2015. In SPVATS, an approximately 4-cm incision was made at the 4th or 5th intercostal space between the anterior and posterior axillary lines. A rib spreader was not used at the incision site, and surgical manipulation was performed very carefully in order to avoid contact between surgical instruments and the intercostal nerves. The same surgeon performed surgery on all patients, and analyzed laboratory data before and after surgery. Results Eighty-four patients underwent anatomical lung resection for postoperative pathological stage I lung cancer. The mean wound length was 4.2 cm. Eighty-four patients underwent lobectomy and segmentectomy, respectively. The mean preoperative forced expiratory volume in 1 second (FEV1%) was 1.85%±0.36%. Our patients consisted of 49 men (58.3%) and 35 women (41.7%), with 64, 18, 1, and 1 having adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and small-cell lung cancer, respectively. The mean operative time was 175±21 min, operative blood loss 92±18 mL, and duration of drain placement 1.9±0.6 days. The duration of the postoperative hospital stay was 7.1±1.7 days, numeric rating scale (NRS) 1 week after surgery 2.8±0.6, and occurrence rate of allodynia 1 month after surgery 10.7%. No patient developed serious

  6. Initial clinical experience with a radiation oncology dedicated open 1.0T MR-simulation.

    Glide-Hurst, Carri K; Wen, Ning; Hearshen, David; Kim, Joshua; Pantelic, Milan; Zhao, Bo; Mancell, Tina; Levin, Kenneth; Movsas, Benjamin; Chetty, Indrin J; Siddiqui, M Salim


    The purpose of this study was to describe our experience with 1.0T MR-SIM including characterization, quality assurance (QA) program, and features necessary for treatment planning. Staffing, safety, and patient screening procedures were developed. Utilization of an external laser positioning system (ELPS) and MR-compatible couchtop were illustrated. Spatial and volumetric analyses were conducted between CT-SIM and MR-SIM using a stereotactic QA phantom with known landmarks and volumes. Magnetic field inhomogeneity was determined using phase difference analysis. System-related, in-plane distortion was evaluated and temporal changes were assessed. 3D distortion was characterized for regions of interest (ROIs) 5-20 cm away from isocenter. American College of Radiology (ACR) recommended tests and impact of ELPS on image quality were analyzed. Combined ultrashort echotime Dixon (UTE/Dixon) sequence was evaluated. Amplitude-triggered 4D MRI was implemented using a motion phantom (2-10 phases, ~ 2 cm excursion, 3-5 s periods) and a liver cancer patient. Duty cycle, acquisition time, and excursion were evaluated between maximum intensity projection (MIP) datasets. Less than 2% difference from expected was obtained between CT-SIM and MR-SIM volumes, with a mean distance of 3D geometric distortion was 0.59 ± 0.32 mm (maximum = 1.65 mm) and increased 10-15 cm from isocenter (mean = 1.57 ± 1.06 mm, maximum = 6.26 mm). ELPS interference was within the operating frequency of the scanner and was characterized by line patterns and a reduction in signal-to-noise ratio (4.6-12.6% for TE = 50-150 ms). Image quality checks were within ACR recommendations. UTE/Dixon sequences yielded detectability between bone and air. For 4D MRI, faster breathing periods had higher duty cycles than slow (50.4% (3 s) and 39.4% (5 s), p < 0.001) and ~fourfold acquisition time increase was measured for ten-phase versus two-phase. Superior-inferior object extent was underestimated 8% (6 mm) for two


    Ye. L. Choinzonov


    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  8. RM de cuerpo entero, experiencia inicial Whole body MRI, initial experience

    Ezequiel Rombolá


    Full Text Available Objetivo: Exponer y compartir nuestra experiencia en resonancia magnética de cuerpo entero (RMCE. Material y métodos: Se realizó estudio prospectivo entre octubre de 2005 y mayo de 2007 sobre 165 RMCE. Edad de los pacientes: 21 y 85 años, media de 51,64. Se utilizó equipo de 1,5 Tesla de campo magnético y tabla deslizable. El protocolo de estudio estuvo integrado por cortes coronales multicontraste (T1, T2 y STIR, axiales y sagitales en T2. Resultados: Se obtuvieron 140 (84,84 % estudios con hallazgos relevantes y 25 (15,15 % sin alteraciones. Se halló predominancia de enfermedades degenerativas articulares del esqueleto axial en 94 pacientes (56,96% sin diferencias significativas entre sexos. Trece pacientes realizaron controles oncológicos demostrándose diseminación a distancia en 6 estudios. En 1 examen se registró la distribución de polimiositis. Conclusiones: La RMCE no representa solamente una innovadora herramienta diagnóstica, sino también ostenta el potencial de competir con metodologías preexistentes en aplicaciones oncológicas y no oncológicas. La sensibilidad y especificidad del método están probadas, pero su aplicación se encuentra limitada por el alto costo y la falta de inclusión en protocolos diagnósticos de estadificación tumoral.Objective: To expose and share our experience in whole-body MRI. Material and methods: A prospective study of 165 whole-body MRI was made from october 2005 to may 2007. The age range was between 21 to 85 years old, with a mean age of 51, 64. A 1.5 Tesla MRI scan was utilized with a table-top movement. Multicontrast coronal scans (T1, T2 and STIR, sagittal and axial T2 compose the study protocol. Results: 140 (84,84 % scans with relevant results and 25 (15,15 % without abnormalities were found. The axial skeletal articular degenerative disease prevalence on 94 (56,96 % cases, without significant difference. Six MRI scans showed secondary dissemination of the oncology disease in a

  9. Intraoperative neuropathology of glioma recurrence: cell detection and classification

    Abas, Fazly S.; Gokozan, Hamza N.; Goksel, Behiye; Otero, Jose J.; Gurcan, Metin N.


    Intraoperative neuropathology of glioma recurrence represents significant visual challenges to pathologists as they carry significant clinical implications. For example, rendering a diagnosis of recurrent glioma can help the surgeon decide to perform more aggressive resection if surgically appropriate. In addition, the success of recent clinical trials for intraoperative administration of therapies, such as inoculation with oncolytic viruses, may suggest that refinement of the intraoperative diagnosis during neurosurgery is an emerging need for pathologists. Typically, these diagnoses require rapid/STAT processing lasting only 20-30 minutes after receipt from neurosurgery. In this relatively short time frame, only dyes, such as hematoxylin and eosin (H and E), can be implemented. The visual challenge lies in the fact that these patients have undergone chemotherapy and radiation, both of which induce cytological atypia in astrocytes, and pathologists are unable to implement helpful biomarkers in their diagnoses. Therefore, there is a need to help pathologists differentiate between astrocytes that are cytologically atypical due to treatment versus infiltrating, recurrent, neoplastic astrocytes. This study focuses on classification of neoplastic versus non-neoplastic astrocytes with the long term goal of providing a better neuropathological computer-aided consultation via classification of cells into reactive gliosis versus recurrent glioma. We present a method to detect cells in H and E stained digitized slides of intraoperative cytologic preparations. The method uses a combination of the `value' component of the HSV color space and `b*' component of the CIE L*a*b* color space to create an enhanced image that suppresses the background while revealing cells on an image. A composite image is formed based on the morphological closing of the hue-luminance combined image. Geometrical and textural features extracted from Discrete Wavelet Frames and combined to classify

  10. Ultrasound-guided Breast Biopsy in the Resource-limited Setting: An Initial Experience in Rural Uganda

    Christopher R. Stark


    Full Text Available Purpose: To describe the methodology and initial experience behind creation of an ultrasoundguided percutaneous breast core biopsy program in rural Uganda. Methods and Materials: Imaging the World Africa (ITWA is the registered non-governmental organization division of Imaging the World (ITW, a not-for-profit organization whose primary aim is the integration of affordable high-quality ultrasound into rural health centers. In 2013, ITWA began the pilot phase of an IRB-approved breast care protocol at a rural health center in Uganda. As part of the protocol’s diagnostic arm, an ultrasound-guided percutaneous breast core biopsy training curriculum was implemented in tandem with creation of regionally supplied biopsy kits. Results: A surgeon at a rural regional referral hospital was successfully trained and certified to perform ultrasound-guided percutaneous breast core biopsies. Affordable and safe biopsy kits were created using locally available medical supplies with the cost of each kit totaling $10.62 USD. Conclusion: Successful implementation of an ultrasound-guided percutaneous breast core biopsy program in the resource-limited setting is possible and can be made sustainable through incorporation of local health care personnel and regionally supplied biopsy materials. Our hope is that ITWA’s initial experience in rural Uganda can serve as a model for similar programs in the future.

  11. Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience

    Wurm, R.E.; Gum, F.; Erbel, S. [Charite Campus Mitte, Berlin (Germany). Dept. of Radiation Oncology


    To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac{sup R} X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac{sup R} Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within {+-}1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.

  12. The experimental investigation of glioma-trophic capacity of human umbilical cord-derived mesenchymal stem cells after intraventricular administration

    FAN Cun-gang


    Full Text Available Objective To explore the glioma-trophic migration capacity of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs by intraventricular administration. Methods The umbilical cord tissue were obtained during full-term pregnancy cesarean section under sterile conditions. This study was approved by Ethics Committee and got the informed consent of patient. The hUC-MSCs were isolated by trypsin and collagenase digestion, followed by adherent culture methods. The characteristics of isolated hUC-MSCs were demonstrated by cell morphylogy, phenotype analysis and multi-differentiation potentials into adipocytes, osteoblasts and neural cells. Then the hUC-MSCs were labeled with CM-DiI and injected into contralateral ventricle of glioma of the C6 glioma-bearing Sprague-Dawley (SD rats. Two weeks later, the rats were sacrificed and the brains were taken out to examine the migration and distribution of hUC-MSCs in the tumor bed, at the interface of tumor and cerebral parenchyma as well as the tumor satelites infiltrating into the normal brain. Results The hUC-MSCs demonstrated plastic-adherent characterization and homogeneous fibroblastic-like morphylogy in culture, expression of specific surface phenotypes of MSCs (CD13, CD29, CD44, CD90 but not endothelial or hematopoietic markers (CD14, CD31, CD34, CD38, CD45, CD133, and muti-differentiatiation potentials into Oil red O stained adipocytes, Alizarin red S stained osteoblasts, neuron-specific enolase (NSE-positive neurons and glial fibrillary acidic protein (GFAP-positive astrocytes in permissive inducive conditions. Importantly, after labeled hUC-MSCs injection into contralateral ventricle of glioma, the hUC-MSCs migrated from initial injection site to the glioma mass and along the interface of tumor and brain, and some of them "chasing" the glioma satellites infiltrated into the normal parenchyma. Conclusion The hUC-MSCs possess prominent tumor-specific targeting capacity and extensive intratumoral

  13. Low-grade glioma: supratentorial astrocytoma, oligodendroglioma, and oligoastrocytoma in adults.

    Ashby, Lynn S; Shapiro, William R


    Low-grade glioma is not a single diagnosis but a category of biologically diverse neoplasms. They are indolent, progressive, and, following anaplastic transformation, invariably fatal. Neuro-oncologists have not established a treatment standard for these tumors. However, it is clear that "low-grade" is not synonymous with "benign," and treatment is required sometime in the course of the disease. Previously, achieving a consensus had been limited by a lack of class I evidence. Physicians treated patients based on retrospective series and personal experience. Currently, results from prospective clinical trials are becoming available. These studies have provided data that may serve as treatment guidelines. Additional results regarding the identification of prognostic variables have raised more questions to be answered. Attention is now directed to the importance of translational research to better define these neoplasms. In the future, it will be necessary to distinguish among low-grade gliomas and identify therapies that may differ between them.

  14. Conditioned medium from neural stem cells inhibits glioma cell growth.

    Li, Z; Zhong, Q; Liu, H; Liu, P; Wu, J; Ma, D; Chen, X; Yang, X


    Malignant glioma is one of the most common brain tumors in the central nervous system. Although the significant progress has been made in recent years, the mortality is still high and 5-year survival rate is still very low. One of the leading causes to the high mortality for glioma patients is metastasis and invasion. An efficient method to control the tumor metastasis is a promising way to treat the glioma. Previous reports indicated that neural stem cells (NSCs) were served as a delivery vector to the anti-glioma therapy. Here, we used the conditioned medium from rat NSCs (NSC-CM) to culture the human glioblastoma cell lines. We found that NSC-CM could inhibit the glioma cell growth, invasion and migration in vitro and attenuate the tumor growth in vivo. Furthermore, this anti-glioma effect was mediated by the inactivation of mitogen activated protein kinase (MAPK) pathway. Above all, this study provided the direct evidence to put forward a simple and efficient method in the inhibition of glioma cells/tumor growth, potentially advancing the anti-glioma therapy.

  15. Expression and prognostic value of JAM-A in gliomas

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H


    in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes...

  16. Repeating hemorrhage after radiotherapy for glioma. Radiological and histological observations

    Kawano, Hirokazu [Miyakonojo Medical Association Hospital, Miyazaki (Japan); Wakisaka, Shinichiro; Kubota, Toshihiko; Hosotani, Kazuo


    A case of radiation necrosis which was observed six years after radiotherapy for a glioma in the right parietal lobe is reported. This patient developed hemiparesis, and radiological examinations showed similar findings consisted with recurrent glioma. Histological examination disclosed that the lesion is correspond to the radiation necrosis. (author)

  17. A role for ion channels in perivascular glioma invasion.

    Thompson, Emily G; Sontheimer, Harald


    Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuropeptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials.

  18. Vasculogenic mimicry:a novel target for glioma therapy

    Yin-Sheng Chen; Zhong-Ping Chen


    Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cel-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cels, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especialy in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fuly understood, glioma stem cels might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and chalenges of VM in gliomas.

  19. Interaction between 5 genetic variants and allergy in glioma risk

    Schoemaker, Minouk J; Robertson, Lindsay; Wigertz, Annette


    The etiology of glioma is barely known. Epidemiologic studies have provided evidence for an inverse relation between glioma risk and allergic disease. Genome-wide association data have identified common genetic variants at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756...


    Irina A. Kurus


    Full Text Available The purpose of article is identification of an actual problem of psychological science: correlation of crises and a crisis experiences with and orientation of time perspective at the initial stage of training in institution of higher education.Methods. During the research the following psychodiagnostic methods are applied: the questionnaire of crisis experiences for student by V. R. Manukyan; a questionnaire of time perspective by F. Zimbardo in adaptation of A. Syrtsova, E. T. Sokolova, O. V. Mitina (ZTPI.Results and scientific novelty. Data on interrelation of crises and crisis experiences with an orientation of temporary prospect are obtained and analysed on the basis of representative selection of students in Novosibirsk State Medical University. Gender distinctions of crises behaviour of students are shown. It is established that temporary prospects «The negative past» and «The fatalistic present» correlate with all the crisis experiences of students at the initial stage of training in higher education institution. The temporary prospect «Future» has the return correlation with crisis experience «absence of the appreciably attractive purposes in the future», and the interrelation with crises is absent. In this regard the author proposes the correction procedure of psychological escort of first-year students.Practical significance. The research findings can be used by educational psychologists for psychological diagnostics of pupils, to search the reasons of their poor progress, during the developing and correction of programs of psychology and pedagogical escort of first-year students, in particular when writing the program of adaptive training in the centers of psychosocial maintenance of the trainees. Guidelines for a choice of the techniques and methods promoting overcoming of the problems connected with crisis of identity and biographic crises are given.

  1. MicroRNA-9 inhibits vasculogenic mimicry of glioma cell lines by suppressing Stathmin expression.

    Song, Yuwen; Mu, Luyan; Han, Xuezhe; Li, Qingla; Dong, Baijing; Li, Hulun; Liu, Xiaoqian


    The purpose of this study was to investigate the functions of microRNA-9, which is a tissue-specific microRNA in central nervous system, in the vasculogenic mimicry (VM) of glioma cell lines in vitro and in vivo. Glioma cell lines U87MG, U251 and SHG44 were transfected with microRNA-9 mimic, microRNA-9 inhibitor or scramble sequences. The amount of microRNA-9 and Stathmin (STMN1) mRNA was determined by quantitative real-time PCR, and the protein expression of STMN1 was determined by western blot. Cell proliferation and apoptosis were assessed. The interactions between the 3'UTR of STMN1 and miR-9 was determined by luciferase reporter assay. The VM capacity in vitro was evaluated using VM formation assay, and the rescue experiment of STMN1 was carried out in U251 cells. The in vivo experiment was applied with animal models implanted with U87MG cells.MicroRNA-9 mimic transfection reduced proliferation and increased apoptosis in glioma cell lines (p < 0.05). MicroRNA-9 mimic up-regulated STMN1 mRNA levels but reduced its protein levels (p < 0.05), and luciferase activity of STMN1 was suppressed by microRNA-9 mimic transfection (p < 0.05). Furthermore, microRNA-9 mimic transfection suppressed tumor volume growth, as well as VM both in vitro and in vivo. The cell viability and microtube density were upregulated in U251 cells after STMN1 up-regulation (p < 0.05). STMN1 is a target of microRNA-9, and microRNA-9 could modulate cell proliferation, VM and tumor volume growth through controlling STMN1 expression. MicroRNA-9 and its targets may represent a novel panel of molecules for the development of glioma treatment.

  2. Sulfasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas.

    Robe, Pierre A; Nguyen-Khac, Minh-Tuan; Lambert, Frederic; Lechanteur, Chantal; Jolois, Olivier; Ernst-Gengoux, Patricia; Rogister, Bernard; Bours, Vincent


    The efficacy of HSV-TK/ganciclovir-based gene therapy on malignant gliomas largely relies on the amplitude of the bystander effect. In these experiments, the anti-inflammatory drug Sulfasalazine increased the HSV-TK/ganciclovir bystander effect in C6, 9L and LN18 cells but not in U87 glioma cells. Using bi-compartmental culture devices and conditioned medium transfer experiments, we showed that in C6, 9L and LN18 cells but not in U87 cells, Sulfasalazine also unveiled a new, contact-independent mechanism of HSV-TK/ganciclovir bystander effect. Upon treatment with ganciclovir, human LN18-TK but not U87-TK cells synthetized and released TNF-alpha in the culture medium. Sulfasalazine sensitized glioma cells to the toxic effect of TNF-alpha and enhanced its secretion in LN18-TK cells in response to GCV treatment. The caspase-8 inhibitor Z-IETD-FMK and a blocking antibody to TNF-alpha both inhibited the contact-independent bystander effect in LN18 cells. Taken together, these results suggest that TNF-alpha mediates the contact-independent bystander effect in LN18 cells. The treatment with GCV and/or Sulfasalazine of tumor xenografts consisting of a mix of 98% C6 and 2% C6-TK cells shows that Sulfasalazine is also a potent adjunct to the in vivo treatment of gliomas.

  3. Glioma Association and Balancing Selection of ZFPM2.

    Shui-Ying Tsang

    Full Text Available ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350, non-glioma cancer (n = 354 and healthy control (n = 463 by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69 of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016, and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005 or non-glioma cancers (P = 0.020. ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002, with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028. In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

  4. Clinical significance of vasculogenic mimicry in human gliomas.

    Liu, Xiao-mei; Zhang, Qing-ping; Mu, Yong-gao; Zhang, Xiang-hen; Sai, Ke; Pang, Jesse Chung-Sean; Ng, Ho-Keung; Chen, Zhong-ping


    Vasculogenic mimicry (VM) is known as non-endothelial tumor cell-lined microvascular channels in aggressive tumors. We have previously found the presence of VM in high-grade gliomas. In this study, we aimed to identify VM patterns in gliomas and to explore their clinical significance. Tumor samples as well as their detailed clinical/prognostic data were collected from 101 patients. Vasculogenic mimicry in the glioma samples was determined by dual staining for endothelial marker CD34 and periodic acid-Schiff (PAS). Tumor samples were also immunohistochemically stained for Ki-67, VEGF, COX-2 and MMP-9. The association between VM and the clinical characteristics of the patients were analyzed. A Kaplan-Meier survival analysis and log-rank tests were performed to compare survival times of the patients. Vasculogenic mimicry was present in 13 out of 101 samples. The higher grade gliomas had a higher incidence of VM than that of lower grade gliomas (P = 0.006). Vasculogenic mimicry channels were associated with the expression of COX-2 and MMP-9 (P age and preoperative epilepsy of the patients, or expression of Ki-67 and VEGF. However, patients with VM-positive gliomas survived a shorter period of time than those with VM negative gliomas (P = 0.027). Interestingly, in high-grade gliomas, the level of microvascular density was lower in VM positive tumors than those VM negative tumors (P = 0.039). Our results suggest that VM channels in gliomas correlate with increasing malignancy and higher aggressiveness, and may provide a complementation to the tumor's blood supply, especially in less vascularized regions, which may aid in the identification of glioma patients with a poorer prognosis.

  5. Long Non-Coding RNAs: The Key Players in Glioma Pathogenesis

    Kiang, Karrie Mei-Yee; Zhang, Xiao-Qin; Leung, Gilberto Ka-Kit, E-mail: [Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong (China)


    Long non-coding RNAs (LncRNAs) represent a novel class of RNAs with no functional protein-coding ability, yet it has become increasingly clear that interactions between lncRNAs with other molecules are responsible for important gene regulatory functions in various contexts. Given their relatively high expressions in the brain, lncRNAs are now thought to play important roles in normal brain development as well as diverse disease processes including gliomagenesis. Intriguingly, certain lncRNAs are closely associated with the initiation, differentiation, progression, recurrence and stem-like characteristics in glioma, and may therefore be exploited for the purposes of sub-classification, diagnosis and prognosis. LncRNAs may also serve as potential therapeutic targets as well as a novel biomarkers in the treatment of glioma. In this article, the functional aspects of lncRNAs, particularly within the central nervous system (CNS), will be briefly discussed, followed by highlights of the important roles of lncRNAs in mediating critical steps during glioma development. In addition, the key lncRNA players and their possible mechanistic pathways associated with gliomagenesis will be addressed.

  6. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Eliane C. Miotto


    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  7. Neurofibromatosis type 1 associated low grade gliomas : A comparison with sporadic low grade gliomas

    Helfferich, Jelte; Nijmeijer, Ronald; Brouwer, Oebele F.; Boon, Maartje; Fock, Annemarie; Hoving, Eelco W.; Meijer, Lisethe; den Dunnen, Wilfred F. A.; de Bont, Eveline S. J. M.


    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including cafe-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which

  8. Reactor physics studies for the Advanced Fuel Cycle Initiative (AFCI) Reactor-Accelerator Coupling Experiments (RACE) Project

    Stankovskiy, Evgeny Yuryevich

    In the recently completed RACE Project of the AFCI, accelerator-driven subcritical systems (ADS) experiments were conducted to develop technology of coupling accelerators to nuclear reactors. In these experiments electron accelerators induced photon-neutron reactions in heavy-metal targets to initiate fission reactions in ADS. Although the Idaho State University (ISU) RACE ADS was constructed only to develop measurement techniques for advanced experiments, many reactor kinetics experiments were conducted there. In the research reported in this dissertation, a method was developed to calculate kinetics parameters for measurement and calculation of the reactivity of ADS, a safety parameter that is necessary for control and monitoring of power production. Reactivity is measured in units of fraction of delayed versus prompt neutron from fission, a quantity that cannot be directly measured in far-subcritical reactors such as the ISU RACE configuration. A new technique is reported herein to calculate it accurately and to predict kinetic behavior of a far-subcritical ADS. Experiments conducted at ISU are first described and experimental data are presented before development of the kinetic theory used in the new computational method. Because of the complexity of the ISU ADS, the Monte-Carlo method as applied in the MCNP code is most suitable for modeling reactor kinetics. However, the standard method of calculating the delayed neutron fraction produces inaccurate values. A new method was developed and used herein to evaluate actual experiments. An advantage of this method is that its efficiency is independent of the fission yield of delayed neutrons, which makes it suitable for fuel with a minor actinide component (e.g. transmutation fuels). The implementation of this method is based on a correlated sampling technique which allows the accurate evaluation of delayed and prompt neutrons. The validity of the obtained results is indicated by good agreement between experimental



    ICE was built in 1977, in a record time of 9 months, using the modified bending magnets of the g-2 muon storage ring. Its purpose was to verify the validity of stochastic and electron cooling for the antiproton project, to be launched in 1978. Already early in 1978, stochastic cooling proved a resounding success, such that the antiproton (p-pbar)project was entirely based on it. Tests of electron cooling followed later: protons of 46 MeV kinetic energy were cooled with an electron beam of 26 kV and 1.3 A. The cage seen prominently in the foreground houses the HV equipment, adjacent to the "cooler" installed in a straight section of the ring. With some modifications, the cooler was later transplanted into LEAR (Low Energy Antiproton Ring) and then, with further modifications, into the AD (Antiproton Decelerator), where it cools antiprotons to this day (2006). See also: 7711282, 7802099, 7908242.

  10. Initial experience of dual-energy lung perfusion CT using a dual-source CT system in children

    Goo, Hyun Woo [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea)


    Initial experience of dual-source dual-energy (DE) lung perfusion CT in children is described. In addition to traditional identification of pulmonary emboli, the assessment of lung perfusion is technically feasible with dual-source DE CT in children with acceptable radiation dose. This article describes how to perform dual-source DE lung perfusion CT in children, including the optimization of intravenous injection method and CT dose parameters. How to produce weighted-average CT images for the assessment of pulmonary emboli and colour-coded perfusion maps for the assessment of regional lung perfusion is also detailed. Lung perfusion status can then be evaluated on perfusion maps by means of either qualitative or quantitative analysis. Potential advantages and disadvantages of this emerging CT technique compared to lung perfusion scintigraphy and cardiac MRI are discussed. (orig.)

  11. Initial results of a model rotor higher harmonic control (HHC) wind tunnel experiment on BVI impulsive noise reduction

    Splettstoesser, W. R.; Lehmann, G.; van der Wall, B.


    Initial acoustic results are presented from a higher harmonic control (HHC) wind tunnel pilot experiment on helicopter rotor blade-vortex interaction (BVI) impulsive noise reduction, making use of the DFVLR 40-percent-scaled BO-105 research rotor in the DNW 6m by 8m closed test section. Considerable noise reduction (of several decibels) has been measured for particular HHC control settings, however, at the cost of increased vibration levels and vice versa. The apparently adverse results for noise and vibration reduction by HHC are explained. At optimum pitch control settings for BVI noise reduction, rotor simulation results demonstrate that blade loading at the outer tip region is decreased, vortex strength and blade vortex miss-distance are increased, resulting altogether in reduced BVI noise generation. At optimum pitch control settings for vibration reduction adverse effects on blade loading, vortex strength and blade vortex miss-distance are found.

  12. Multimedia materials for education, training, and advocacy in international health: experiences with the Schistosomiasis Control Initiative CD-ROM

    TJ Beanland


    Full Text Available We describe an innovative use of multimedia materials to support training and advocacy within a schistosomiasis control programme. The Schistosomiasis Control Initiative (SCI at Imperial College London works with selected sub-Saharan African countries to develop schistosomiasis control programmes. Two elements of the SCI programme were supported by multimedia materials developed at the Wellcome Trust in collaboration with the SCI: (1 training of programme managers, district health officers, and those delivering practical elements of the programme; and (2 advocacy targeted at decision-makers and donors. Evaluation of the materials revealed high reported ratings for both user satisfaction and impact from use of the product. From this experience we draw out several general messages about development of multimedia materials and how these will play a growing future role in promoting training within international health.

  13. Multimedia materials for education, training, and advocacy in international health: experiences with the Schistosomiasis Control Initiative CD-ROM.

    Beanland, T J; Lacey, S D; Melkman, D D; Palmer, S; Stothard, J R; Fleming, F; Fenwick, A


    We describe an innovative use of multimedia materials to support training and advocacy within a schistosomiasis control programme. The Schistosomiasis Control Initiative (SCI) at Imperial College London works with selected sub-Saharan African countries to develop schistosomiasis control programmes. Two elements of the SCI programme were supported by multimedia materials developed at the Wellcome Trust in collaboration with the SCI: (1) training of programme managers, district health officers, and those delivering practical elements of the programme; and (2) advocacy targeted at decision-makers and donors. Evaluation of the materials revealed high reported ratings for both user satisfaction and impact from use of the product. From this experience we draw out several general messages about development of multimedia materials and how these will play a growing future role in promoting training within international health.

  14. PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas.

    Shunsuke Nakae

    Full Text Available Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1 mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS and overall survival (OS of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

  15. Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies.

    Barbosa, Breno José Alencar Pires; Mariano, Eric Domingos; Batista, Chary Marquez; Marie, Suely Kazue Nagahashi; Teixeira, Manoel Jacobsen; Pereira, Carlos Umberto; Tatagiba, Marcos Soares; Lepski, Guilherme Alves


    Several studies published to date about glioma surgery have addressed the validity of using novel technologies for intraoperative guidance and potentially improved outcomes. However, most of these reports are limited by questionable methods and/or by their retrospective nature. In this work, we performed a systematic review of the literature to address the impact of intraoperative assistive technologies on the extent of resection (EOR) in glioma surgery, compared to conventional unaided surgery. We were also interested in two secondary outcome variables: functional status and progression-free survival. We primarily used PubMed to search for relevant articles. Studies were deemed eligible for our analysis if they (1) were prospective controlled studies; (2) used EOR as their primary target outcome, assessed by MRI volumetric analysis; and (3) had a homogeneous study population with clear inclusion criteria. Out of 493 publications identified in our initial search, only six matched all selection criteria for qualitative synthesis. Currently, the evidence points to 5-ALA, DTI functional neuronavigation, neurophysiological monitoring, and intraoperative MRI as the best tools for improving EOR in glioma surgery. Our sample and conclusions were limited by the fact that studies varied in terms of population characteristics and in their use of different volumetric analyses. We were also limited by the low number of prospective controlled trials available in the literature. Additional evidence-based high-quality studies assessing cost-effectiveness should be conducted to better determine the benefits of intraoperative assistive technologies in glioma surgery.

  16. The mediating effect of depressive symptoms on the relationship between traumatic childhood experiences and drug use initiation.

    Fishbein, Diana; Novak, Scott P; Krebs, Christopher; Warner, Tara; Hammond, Jane


    Stressful experiences such as childhood trauma and depressive symptoms have both been implicated in the initiation of drug use; however, longitudinal designs have not yet been used to elucidate their respective roles to better understand the causal sequence. In the present study, a sensitivity analysis was conducted using two mediation strategies to examine how this sequence may differ by various levels of statistical control, including (1) the standard mediational model in which the effect of lifetime traumatic stressors (Year 1) on the onset of drug use (Years 3 and 4) is mediated by levels of depressive symptoms (Year 2); and (2) a stronger test of causality such that the effect of lifetime traumatic stressors (Year 1) on the onset of drug use (Years 3 and 4) was mediated by changes in depressive symptoms (Year 1 to 2), measured by a residualized change score that controlled for levels in Year 1. Two types of trauma were studied in a community-based study of 489 Hispanic preadolescents (aged 10-12): (a) the number of lifetime traumatic stressors and (b) seven specific lifetime stressors. We also controlled for new onset traumatic stressors occurring between Years 1 and 2. Primary findings indicate that drug use initiation during early adolescence (e.g., ages 14-16) may not be tied to immediate proximal perturbations in risk factors, such as traumatic experiences and depressive symptoms. Rather, the effects of trauma on depression in this sample appear to be established earlier in childhood (ages 10-14 or younger) and persist in a relatively stable manner into middle adolescence when the risk for drug use may be heightened. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. The initial magnetic susceptibility of polydisperse ferrofluids: A comparison between experiment and theory over a wide range of concentration

    Solovyova, Anna Y.; Goldina, Olga A.; Ivanov, Alexey O.; Lebedev, Aleksandr V.; Elfimova, Ekaterina A.


    Temperature dependencies of the static initial magnetic susceptibility for ferrofluids at various concentrations are studied using experiment and statistical-mechanical theories. Magnetic susceptibility measurements are carried out for twelve samples of magnetite-based fluids stabilized with oleic acid over a wide range of temperatures (210 K ≲T ≲ 390 K); all samples have the same granulometric composition but different volume ferroparticle concentrations (0.2 ≲ φ ≲ 0.5). Experimental results are analyzed using three theories: the second-order modified mean-field theory (MMF2) [A. O. Ivanov and O. B. Kuznetsova, Phys. Rev. E 64, 41405 (2001)]; its correction for polydisperse ferrofluids arising from Mayer-type cluster expansion and taking into account the first terms of the polydisperse second virial coefficient [A. O. Ivanov and E. A. Elfimova, J. Magn. Magn. Mater 374, 327 (2015)]; and a new theory based on MMF2 combined with the first terms of the polydisperse second and third virial contributions to susceptibility. It turns out that the applicability of each theory depends on the experimental sample density. If twelve ferrofluid samples are split into three groups of strong, moderate, and low concentrated fluids, the temperature dependences of the initial magnetic susceptibility in each group are very precisely described by one of the three theories mentioned above. The determination of a universal formula predicting a ferrofluid susceptibility over a broad range of concentrations and temperatures remains as a challenge.

  18. The Joint Experiment for Crop Assessment and Monitoring (JECAM) Initiative: Developing methods and best practices for global agricultural monitoring

    Champagne, C.; Jarvis, I.; Defourny, P.; Davidson, A.


    Agricultural systems differ significantly throughout the world, making a 'one size fits all' approach to remote sensing and monitoring of agricultural landscapes problematic. The Joint Experiment for Crop Assessment and Monitoring (JECAM) was established in 2009 to bring together the global scientific community to work towards a set of best practices and recommendations for using earth observation data to map, monitor and report on agricultural productivity globally across an array of diverse agricultural systems. These methods form the research and development component of the Group on Earth Observation Global Agricultural Monitoring (GEOGLAM) initiative to harmonize global monitoring efforts and increase market transparency. The JECAM initiative brings together researchers from a large number of globally distributed, well monitored agricultural test sites that cover a range of crop types, cropping systems and climate regimes. Each test site works independently as well as together across multiple sites to test methods, sensors and field data collection techniques to derive key agricultural parameters, including crop type, crop condition, crop yield and soil moisture. The outcome of this project will be a set of best practices that cover the range of remote sensing monitoring and reporting needs, including satellite data acquisition, pre-processing techniques, information retrieval and ground data validation. These outcomes provide the research and development foundation for GEOGLAM and will help to inform the development of the GEOGLAM "system of systems" for global agricultural monitoring. The outcomes of the 2014 JECAM science meeting will be discussed as well as examples of methods being developed by JECAM scientists.

  19. Initial Experience with Percutaneous Needle Aspiration of Paraspinal Lesions Using XperGuide Cone-Beam CT

    Kim, Si Lip; Park, Hee Jin; Lee, So Yeon; Chung, Eun Chul; Paark, Hae Won; Kook, Shin Ho; Rho, Myung Ho [Dept. of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    The aim of this study is to report our initial experience using XperGuide cone-beam computed tomography (CBCT) for percutaneous needle aspiration of the paraspinal lesions. Between September 2011 and September 2012, 12 patients who underwent percutaneous needle aspiration of the paraspinal lesions for suspected pyogenic spondylitis, tuberculous spondylitis, or metastasis were included. The procedure was performed on the XperGuide CBCT. Based on the initial CBCT, target points and entrance were determined, using dedicated guidance software (XperGuide), and the needle pathway was visualized in various reconstructed images. Needle aspiration was performed using Westcott needle and correct needle positioning was confirmed with the second CBCT. The technical success was defined as the needle tip reached within 5 mm of the target point. Culture, smear, and polymerase chain reaction of obtained samples were performed. In all twelve patients, target areas could be determined based on XperCT data and achieved 100% technical success. Diagnosis could be made in 91.7% of cases and the median interventional procedure time was 27.8 minutes. There was no major complication in all patients. Percutaneous needle aspiration of paraspinal lesions using XperGuide CBCT is easy, accurate, safe, and useful in determining the treatment of direction.

  20. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: initial experience in Oaxaca, Mexico.

    García-Matus, Rolando; Hernández-Hernández, Carlos Alberto; Leyva-García, Omar; Vásquez-Ciriaco, Sergio; Flores-Ayala, Guillermo; Navarro-Hernández, Quetzalli; Pérez-Bustamante, Gerardo; Valencia-Mijares, Norma Miriam; Esquivel, Jesus


    Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multimodality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.

  1. An experimental investigation of the dynamics of submarine leveed channel initiation as sediment-laden density currents experience sudden unconfinement

    Rowland, Joel C [Los Alamos National Laboratory; Hilley, George E [STANFORD UNIV; Fildani, Andrea [CHEVRON ETC


    Leveed submarine channels play a critical role in the transfer of sediment from the upper continental slopes to interslope basins and ultimately deepwater settings. Despite a reasonable understanding of how these channels grow once established, how such channels initiate on previously unchannelized portions of the seafloor remains poorly understood. We conducted a series of experiments that elucidate the influence of excess density relative to flow velocity on the dynamics of, and depositional morphologies arising from, density currents undergoing sudden unconfinement across a sloped bed. Experimental currents transported only suspended sediment across a non-erodible substrate. Under flow conditions ranging from supercritical to subcritical (bulk Richardson numbers of 0.02 to 1.2) our experiments failed to produce deposits resembling or exhibiting the potential to evolve into self-formed leveed channels. In the absence of excess density, a submerged sediment-laden flow produced sharp crested lateral deposits bounding the margins of the flow for approximately a distance of two outlet widths down basin. These lateral deposits terminated in a centerline deposit that greatly exceeded marginal deposits in thickness. As excess density increased relative to the outlet velocity, the rate of lateral spreading of the flow increased relative to the downstream propagation of the density current, transitioning from a narrow flow aligned with the channel outlet to a broad radially expanding flow. Coincident with these changes in flow dynamics, the bounding lateral deposits extended for shorter distances, had lower, more poorly defined crests that were increasingly wider in separation than the initial outlet, and progressively became more oblong rather than linear. Based on our results, we conclude that leveed channels cannot initiate from sediment-laden density currents under strictly depositional conditions. Partial confinement of these currents appears to be necessary to

  2. Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells

    Chung Heon Ryu


    Full Text Available Temozolomide (TMZ has become a key therapeutic agent in patients with malignant gliomas; however, its survival benefit remains unsatisfactory. Valproic acid (VPA has emerged as an anticancer drug via inhibition of histone deacetylases (HDACs, but the therapeutic advantages of a combination with VPA and TMZ remain poorly understood. The main aim of the present study was to determine whether an antitumor effect could be potentiated by a combination of VPA and TMZ, especially in TMZ-resistant cell lines. A combination of VPA and TMZ had a significantly enhanced antitumor effect in TMZ-resistant malignant glioma cells (T98 and U138. This enhanced antitumor effect correlated with VPA-mediated reduced O6-methylguanine-DNA methyltransferase (MGMT expression, which plays an important role in cellular resistance to alkylating agents. In vitro, the combination of these drugs enhanced the apoptotic and autophagic cell death, as well as suppressed the migratory activities in TMZ-resistant cell lines. Furthermore, in vivo efficacy experiment showed that treatment of combination of VPA and TMZ significantly inhibited tumor growth compared with the monotherapy groups of mice. These results suggest that the clinical efficacy of TMZ chemotherapy in TMZ-resistant malignant glioma may be improved by combination with VPA.

  3. Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.

    He, Yan-Qing; Li, Yan; Wang, Xiao-Yu; He, Xiao-Dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-Jing; Yang, Xuesong


    1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis.

  4. Intraoperative direct electrical stimulations of central nervous system during surgery of gliomas near eloquent areas

    WANG Wei-min


    Full Text Available Objective To report our experiences of direct cortical stimulatio