71 research outputs found

    Comparing satellite and helicopter-based methods for observing crevasses, application in East Antarctica

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    Knowing where crevasses are is critical for planning safe on-ice field operations. Previous methods have ranged from real-time imaging of subsurface structures using ground penetrating radar, to mapping of crevasses over large areas using satellite imagery, with each method having it\u27s own strengths and weaknesses. In this paper we compare the detection of crevasses at the Totten Glacier, East Antarctica, from helicopter-borne ground penetrating radar with satellite-based microwave synthetic aperture radar imagery. Our results show that the 80 MHz helicopter-borne ground penetrating radar was able to detect crevasses up to a depth of 70 m, with snow bridge thickness of \u3e30 m. Comparison with TerraSAR-X (X-band, 9.6 GHz) satellite imagery indicates that the latter is highly effective, detecting 100% of crevasses with snow bridges of up to 4m thick and detecting 95% of crevasses with snow bridges up to 10 m thick. The ability of both methods to identify individual crevasses is affected by several factors including crevasse geometry, survey or satellite orientation and snow moisture content, and further experiments are planned to investigate performance under a wider range of conditions

    Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

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    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mgday−1) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1–36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2–104+) weeks and PFS-6 was 14.3% (95% CI 4.0–32.7%). The median overall survival was 24.6 weeks (range 4–104+). No grade 3–4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug

    Gain of FGF4 is a frequent event in KIT/PDGFRA/SDH/RAS-P WT GIST

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    Gastrointestinal stromal tumors (GIST) lacking mutations in KIT/PDGFRA or RAS pathways and retaining an intact SDH complex are usually referred to as KIT/PDGFRA/SDH/RAS-P WT GIST or more simply quadruple WT GIST (~5% of all GIST). Despite efforts made, no recurrent genetic event in quadruple WT GIST has been identified so far. To further investigate this disease, we performed high throughput copy number analysis on quadruple WT GIST specimens identifying a recurrent focal gain in band 11q13.3 (involving FGF3/FGF4) in 6/8 cases. This event was not found in the other molecular GIST subgroups. FGF3/FGF4 duplication was associated with high expression of FGF4, both at mRNA and protein level, a growth factor normally not expressed in adult tissues or in KIT/PDGFRA-mutated GIST. FGFR1 was found to be the predominant FGF receptor expressed and phosphorylation of AKT was detected, suggesting that a FGF4-FGFR1 autocrine loop could stimulate downstream signaling in quadruple WT GIST. Together with the recent reports of quadruple WT cases carrying FGFR1 activating alterations, these findings strengthen the hypothesis of a potential involvement of FGFR pathway deregulation in quadruple WT GIST, which may represent a rationale for novel therapeutic approaches

    Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

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    BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

    Variability and Trends in Physical and Biogeochemical Parameters of the Mediterranean Sea during a Cruise with RV MARIA S. MERIAN in March 2018

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    The last few decades have seen dramatic changes in the hydrography and biogeochemistry of the Mediterranean Sea. The complex bathymetry and highly variable spatial and temporal scales of atmospheric forcing, convective and ventilation processes contribute to generate complex and unsteady circulation patterns and significant variability in biogeochemical systems. Part of the variability of this system can be influenced by anthropogenic contributions. Consequently, it is necessary to document details and to understand trends in place to better relate the observed processes and to possibly predict the consequences of these changes. In this context we report data from an oceanographic cruise in the Mediterranean Sea on the German research vessel Maria S. Merian (MSM72) in March 2018. The main objective of the cruise was to contribute to the understanding of long-term changes and trends in physical and biogeochemical parameters, such as the anthropogenic carbon uptake and to further assess the hydrographical situation after the major climatological shifts in the eastern and western part of the basin, known as the Eastern and Western Mediterranean Transients. During the cruise, multidisciplinary measurements were conducted on a predominantly zonal section throughout the Mediterranean Sea, contributing to the Med-SHIP and GO-SHIP long-term repeat cruise section that is conducted at regular intervals in the Mediterranean Sea to observe changes and impacts on physical and biogeochemical variables. The data can be accessed at https://doi.org/10.1594/PANGAEA.905902 (Hainbucher et al., 2019), https://doi.org/10.1594/PANGAEA.913512 (Hainbucher, 2020a) https://doi.org/10.1594/PANGAEA.913608, (Hainbucher, 2020b) https://doi.org/10.1594/PANGAEA.913505, (Hainbucher, 2020c) https://doi.org/10.1594/PANGAEA.905887 (Tanhua et al., 2019) and https://doi.org/10.25921/z7en-hn85 (Tanhua et al, 2020)

    Integrated genomic study of quadruple-WT GIST (KIT/PDGFRA/SDH/RAS pathway wild-type GIST)

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    BACKGROUND: About 10-15% of adult gastrointestinal stromal tumors (GIST) and the vast majority of pediatric GIST do not harbour KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations (J Clin Oncol 22:3813-3825, 2004; Hematol Oncol Clin North Am 23:15-34, 2009). The molecular biology of these GIST, originally defined as KIT/PDGFRA wild-type (WT), is complex due to the existence of different subgroups with distinct molecular hallmarks, including defects in the succinate dehydrogenase (SDH) complex and mutations of neurofibromatosis type 1 (NF1), BRAF, or KRAS genes (RAS-pathway or RAS-P).In this extremely heterogeneous landscape, the clinical profile and molecular abnormalities of the small subgroup of WT GIST suitably referred to as quadruple wild-type GIST (quadrupleWT or KITWT/PDGFRAWT/SDHWT/RAS-PWT) remains undefined. The aim of this study is to investigate the genomic profile of KITWT/PDGFRAWT/SDHWT/RAS-PWT GIST, by using a massively parallel sequencing and microarray approach, and compare it with the genomic profile of other GIST subtypes. METHODS: We performed a whole genome analysis using a massively parallel sequencing approach on a total of 16 GIST cases (2 KITWT/PDGFRAWT/SDHWT and SDHBIHC+/SDHAIHC+, 2 KITWT/PDGFRAWT/SDHAmut and SDHBIHC-/SDHAIHC- and 12 cases of KITmut or PDGFRAmut GIST). To confirm and extend the results, whole-genome gene expression analysis by microarray was performed on 9 out 16 patients analyzed by RNAseq and an additional 20 GIST patients (1 KITWT/PDGFRAWTSDHAmut GIST and 19 KITmut or PDGFRAmut GIST). The most impressive data were validated by quantitave PCR and Western Blot analysis. RESULTS: We found that both cases of quadrupleWT GIST had a genomic profile profoundly different from both either KIT/PDGFRA mutated or SDHA-mutated GIST. In particular, the quadrupleWT GIST tumors are characterized by the overexpression of molecular markers (CALCRL and COL22A1) and of specific oncogenes including tyrosine and cyclin- dependent kinases (NTRK2 and CDK6) and one member of the ETS-transcription factor family (ERG). CONCLUSION: We report for the first time an integrated genomic picture of KITWT/PDGFRAWT/SDHWT/RAS-PWT GIST, using massively parallel sequencing and gene expression analyses, and found that quadrupleWT GIST have an expression signature that is distinct from SDH-mutant GIST as well as GIST harbouring mutations in KIT or PDGFRA. Our findings suggest that quadrupleWT GIST represent another unique group within the family of gastrointestintal stromal tumors

    miRNAs Expression Analysis in Paired Fresh/Frozen and Dissected Formalin Fixed and Paraffin Embedded Glioblastoma Using Real-Time PCR

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    miRNAs are small molecules involved in gene regulation. Each tissue shows a characteristic miRNAs epression profile that could be altered during neoplastic transformation. Glioblastoma is the most aggressive brain tumour of the adult with a high rate of mortality. Recognizing a specific pattern of miRNAs for GBM could provide further boost for target therapy. The availability of fresh tissue for brain specimens is often limited and for this reason the possibility of starting from formalin fixed and paraffin embedded tissue (FFPE) could very helpful even in miRNAs expression analysis. We analysed a panel of 19 miRNAs in 30 paired samples starting both from FFPE and Fresh/Frozen material. Our data revealed that there is a good correlation in results obtained from FFPE in comparison with those obtained analysing miRNAs extracted from Fresh/Frozen specimen. In the few cases with a not good correlation value we noticed that the discrepancy could be due to dissection performed in FFPE samples. To the best of our knowledge this is the first paper demonstrating that the results obtained in miRNAs analysis using Real-Time PCR starting from FFPE specimens of glioblastoma are comparable with those obtained in Fresh/Frozen samples

    State of the Antarctic and Southern Ocean Climate System

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    This paper reviews developments in our understanding of the state of the Antarctic and Southern Ocean climate and its relation to the global climate system over the last few millennia. Climate over this and earlier periods has not been stable, as evidenced by the occurrence of abrupt changes in atmospheric circulation and temperature recorded in Antarctic ice core proxies for past climate. Two of the most prominent abrupt climate change events are characterized by intensification of the circumpolar westerlies (also known as the Southern Annular Mode) between ∼6000 and 5000 years ago and since 1200–1000 years ago. Following the last of these is a period of major trans-Antarctic reorganization of atmospheric circulation and temperature between A.D. 1700 and 1850. The two earlier Antarctic abrupt climate change events appear linked to but predate by several centuries even more abrupt climate change in the North Atlantic, and the end of the more recent event is coincident with reorganization of atmospheric circulation in the North Pacific. Improved understanding of such events and of the associations between abrupt climate change events recorded in both hemispheres is critical to predicting the impact and timing of future abrupt climate change events potentially forced by anthropogenic changes in greenhouse gases and aerosols. Special attention is given to the climate of the past 200 years, which was recorded by a network of recently available shallow firn cores, and to that of the past 50 years, which was monitored by the continuous instrumental record. Significant regional climate changes have taken place in the Antarctic during the past 50 years. Atmospheric temperatures have increased markedly over the Antarctic Peninsula, linked to nearby ocean warming and intensification of the circumpolar westerlies. Glaciers are retreating on the peninsula, in Patagonia, on the sub-Antarctic islands, and in West Antarctica adjacent to the peninsula. The penetration of marine air masses has become more pronounced over parts of West Antarctica. Above the surface, the Antarctic troposphere has warmed during winter while the stratosphere has cooled year-round. The upper kilometer of the circumpolar Southern Ocean has warmed, Antarctic Bottom Water across a wide sector off East Antarctica has freshened, and the densest bottom water in the Weddell Sea has warmed. In contrast to these regional climate changes, over most of Antarctica, near-surface temperature and snowfall have not increased significantly during at least the past 50 years, and proxy data suggest that the atmospheric circulation over the interior has remained in a similar state for at least the past 200 years. Furthermore, the total sea ice cover around Antarctica has exhibited no significant overall change since reliable satellite monitoring began in the late 1970s, despite large but compensating regional changes. The inhomogeneity of Antarctic climate in space and time implies that recent Antarctic climate changes are due on the one hand to a combination of strong multidecadal variability and anthropogenic effects and, as demonstrated by the paleoclimate record, on the other hand to multidecadal to millennial scale and longer natural variability forced through changes in orbital insolation, greenhouse gases, solar variability, ice dynamics, and aerosols. Model projections suggest that over the 21st century the Antarctic interior will warm by 3.4° ± 1°C, and sea ice extent will decrease by ∼30%. Ice sheet models are not yet adequate enough to answer pressing questions about the effect of projected warming on mass balance and sea level. Considering the potentially major impacts of a warming climate on Antarctica, vigorous efforts are needed to better understand all aspects of the highly coupled Antarctic climate system as well as its influence on the Earth\u27s climate and oceans
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