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

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

The cognitive cerebellum: linking microstructure to cognitive functions in a healthy population

Background The cerebellum is recognized for its role in motor control. However, it also plays a crucial part in modulating circuits involved in cognition and affect. While studies conducted on people with cerebellar disorders highlight both structural and functional links with cognition, research on cerebellar structure in the healthy population remains sparse. To better clarify the cerebellum’s role and operational mode in cognition, this multi-scale study explores the relationship between cognitive functions and cerebellar macrostructure and microstructure in healthy individuals. Macrostructural analysis focused on grey matter (GM) and white matter (WM) volumes, while microstructural evaluation used fractional anisotropy (FA) values. Methods Using a large normative cohort, the study examined cerebellar GM and WM volumes in 151 participants and FA in 83 participants. Cerebellar GM and WM volumes and FA values were correlated voxel-wise against the following cognitive domains: long-term memory, abstract reasoning, language-related executive functions, processing speed, and impulsive decision-making. Results Significant positive correlations were found between FA in specific cerebellar regions and long-term memory (p = 0.030), abstract reasoning (p = 0.048), and language-related executive functions (p = 0.043). Additionally, cerebellar FA values negatively correlated in several clusters with reaction time (p = 0.001; p = 0.026; p = 0.045), indicating faster processing speed with higher FA. No significant associations were found between cerebellar GM/WM volumes and cognitive performance after Family Wise Error correction, except for a positive correlation between WM and reaction time (p = 0.023). Discussion These findings highlight the cerebellum's microstructure role in cognition. FA may reflect the efficiency of communication between cerebellar and cortical regions, thus allowing the cerebellum to improve cognitive performance by updating internal models and correcting discrepancies between predictions and outcomes

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

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

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?

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

Bedmap3 updated ice bed, surface and thickness gridded datasets for Antarctica

We present Bedmap3, the latest suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60 \ub0S. Bedmap3 incorporates and adds to all post-1950s datasets previously used for Bedmap2, including 84 new aero-geophysical surveys by 15 data providers, an additional 52 million data points and 1.9 million line-kilometres of measurement. These efforts have filled notable gaps including in major mountain ranges and the deep interior of East Antarctica, along West Antarctic coastlines and on the Antarctic Peninsula. Our new Bedmap3/RINGS grounding line similarly consolidates multiple recent mappings into a single, spatially coherent feature. Combined with updated maps of surface topography, ice shelf thickness, rock outcrops and bathymetry, Bedmap3 reveals in much greater detail the subglacial landscape and distribution of Antarctica’s ice, providing new opportunities to interpret continental-scale landscape evolution and to model the past and future evolution of the Antarctic ice sheets

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

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

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

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)

Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III

Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9 17, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNA

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

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