Search

Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDH glioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration of D-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1-97.6) and 91.1% (95% CrI, 72.0-97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of 'proneural' and 'stemness' gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDH LGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.

Rapid recognition of elevated intracranial pressure (ICP) is essential to avoid brain stem herniation and death. Brain stem herniation is a very serious disorder in which an excess of intracranial pressure causes part of the brain to be squeezed through the foramen magnum at the base of the skull. Increased pressure on the brain stem can lead to blood pressure and breathing problems and brain death, respiratory or cardiac arrest, permanent brain damage, coma and death. The aim of this work was to evaluate the diagnostic accuracy of using Optic Nerve Sheath Diameter (ONSD) measurements to detect elevated ICP compared to computed tomography (CT) brain scanning. A prospective, observational cross-sectional study of 100 randomly selected ICU patients with suspected elevated ICP at Cairo university hospitals and cardiothoracic surgical ICU of the National Heart Institute (NHI), Cairo, Egypt. Optic nerve ultrasonography (US) was performed on all patients; CT brain scanning was chosen as the gold standard for detecting elevated ICP. Results: the cause of elevated ICP, 51.3% of patients were admitted with head trauma P-value = 0.000, clinical signs of elevated ICP, 31.3% of patients developed convulsions and 26.3% showed Cushing reflex (P=0.004 and 0.010 respectively). Besides the Glasgow Coma Scale (GCS), patients with elevated ICP had a mean GCS score of 7 and patients without elevated ICP had mean GCS of 13 (P˂0.001). Regarding ONSD, mean average ONSD was 6 in patients with elevated ICP and 3.1 in patients without elevated ICP (P˂0.01), receiver operating characteristic (ROC) curve analysis revealed that ONSD greater than 4.31 mm was significant in prediction of elevated ICP compared to CT brain scanning with 94.8% sensitivity and 90.11% specificity. Conclusion: patients’ ONSD is a simple bedside technique that can accurately diagnose of elevated ICP compared to CT brain scanning. The diagnostic accuracy of ONSD using a 4.31 mm cut-off value can diagnose of elevated ICP with 94.8% sensitivity and 90.11% specificity.

Wellbore cleaning is a vital link between drilling operations and well completion to secure the massive time and money invested to drill the hole intervals by removing drilling fluids residues, pipe dope, and other debris from the wellbore. The well production can be sustained in the long-term by properly accomplishing this step, promoting technical and operational efficiencies. This paper presents an effective customized treatment design and successful execution of a wellbore cleaning case study. The Wellbore cleaning process is a combination of both mechanical and chemical means, a cleanout string of scraper, brush, magnets, and pill train of surfactants, and solvents are expected to retrieve debris and displace mud residues leaving the wellbore water wet, whose efficiencies can be judged through return fluids Nephelometric Turbidity Unit (NTU) and Total Suspended Solids (TSS). Since different wells vary in geometry, depths, and mud components, a custom design for the wellbore cleaning process is mandatory to guarantee satisfying treatment outputs, the design includes cleanout string parts and spacing, besides solvents and surfactants pills train additives, and volume. Extensive lab testing was performed to customize the proper wellbore cleaning design to remove inverted emulsion fluids (IEF) residues from casing and tubing in the studied challenge gas well. The casing pickling was executed with 150 barrels (bbl) of solvent and surfactant chemical cleaning Spacers containing 630 gallons (gal) of locally manufactured solvent and 378 gal of locally manufactured surfactant displacing the wellbore water with clean water. The water returns NTU and TSS of 47 and 0.03 % Solids respectively were achieved at 179 bbl after the high viscosity tail spacer of the casing pickling. The Cleanout Bottom Hole Assembly (BHA) was subsequently pulled out of the hole free from IEF residues and water wet, demonstrating the good cleaning performance of the locally formulated Chemistries. Similarly, the Tubing Pickling was executed with 54 bbl of Chemical cleaning spacer containing 990 gal of solvent. The water returns NTU and TSS of 38 and 0.02 % Solids respectively were achieved at 168 bbl after the high viscosity tail Spacer of the tubing pickling. In a conclusion, the low NTU and TSS values confirmed the effective wellbore cleaning design and treatment. In this paper, we will be presenting a custom treatment design and successful execution of a wellbore cleaning case study from a chemical perspective, using 100% locally developed chemistries, that are environmentally friendly and readily available in-country, adding the value of lead time and optimized cost to drilling operations, where selected treatments could achieve targeted return fluids NTU and TSS within competitive displacement volume for both casing and tubing.

In the current study, the accuracy of airborne gravity data is evaluated based on the most recent Global Geopotential Models (GGM) and terrestrial gravity data to find out to what extent these data are acceptable to be used in multi-applications (e. g., geodesy and geophysics). To achieve this goal, the remove-compute-restore (RCR) scheme, upward, and downward continuation operational methods (least square collocation and fast Fourier transform procedures) are applied. The airborne gravity data had been acquired by the Egyptian Nuclear Material Authority (ENMA) in the central-western desert for geological applications. Firstly, three GGMs models (EGM2008, EIGEN-6C4 and XGM2019e up to various degrees) are used to compare with the free-air airborne gravity anomaly, The EGM2008 model up to degree 720 produces the smallest mean and STD difference values with 2.59 and 3.07 mGal, respectively. The terrestrial gravity data are compared with the airborne gravity anomaly at both flight and ground levels. In-flight level, the terrestrial gravity data are upward continued to the flight level and compared with the airborne gravity anomaly. The statistical results show that the mean and STD differences are about 4.2 and 0.75 mGal, respectively. While in-ground level evaluation, two operational techniques are used to downward continue the airborne gravity data (Fast Fourier Transform (FFT) and Least Squares Collocation (LSC)). The combined Satellite model EGM2008 up to degree 720 and SRTM 30 m are used to remove and restore the long and short-wavelength information. It is observed that the collocation gives better statistical results than FFT with mean and STD difference values are about 3.13 and 1.13 and mGal, respectively.

Supplementary Figure 3

Supplementary Figure 5

Supplementary Figure 6

Supplementary Figure 7

Supplementary Figure Legends and Methods

Supplementary Figure 4

Supplementary Figure 2

Supplementary Figure 1

Purpose:Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.Experimental Design:Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies.Results:Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E−15).Conclusions:We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human–mouse matched coclinical trials.

Supplementary Tables

In this work, we develop a new general strategy for fabricating a printable skin-integrated electronics that is highly permeable to gases, inflammation-free, conformable, and biodegradable for monitoring physiological functions.

PURPOSE To compare clinical outcomes in a cohort of patients with advanced non–small-cell lung cancer (NSCLC) with targetable genomic alterations detected using plasma-based circulating tumor DNA (ctDNA) or tumor-based next-generation sequencing (NGS) assays treated with US Food and Drug Administration–approved therapies at a large academic research cancer center. METHODS A retrospective review from our MD Anderson GEMINI database identified 2,224 blood samples sent for ctDNA NGS testing from 1971 consecutive patients with a diagnosis of advanced NSCLC. Clinical, treatment, and outcome information were collected, reviewed, and analyzed. RESULTS Overall, 27% of the ctDNA tests identified at least one targetable mutation and 73% of targetable mutations were EGFR-sensitizing mutations. Among patients treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapies, there were no significant differences in progression-free survival of 379 days and 352 days ( P value = .41) with treatment based on tissue (n = 40) or ctDNA (n = 40), respectively. Additionally, there were no differences in progression-free survival or objective response rate among those with low (n = 8, 0.01%-0.99%) versus high (n = 16, ≥ 1%) levels of ctDNA of the targetable mutation as measured by variant allele frequency (VAF). Overall, there was excellent testing concordance (n = 217 tests) of > 97%, sensitivity of 91.7%, and specificity of 99.7% between blood-based ctDNA NGS and tissue-based NGS assays. CONCLUSION There were no significant differences in clinical outcomes among patients treated with approved EGFR-TKIs whose mutations were identified using either tumor- or plasma-based comprehensive profiling and those with very low VAF as compared with high VAF, supporting the use of plasma-based profiling to guide initial TKI use in patients with metastatic EGFR-mutant NSCLC.

Purpose: Lower grade gliomas (LGGs) are malignant brain tumors. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor grade is associated with contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes. Patients and Methods: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154. Results: Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG in patients with nonenhancing glioma was 18% (one partial response, three minor responses). The median progression-free survival was 36.8 months [95% confidence interval (CI), 11.2–40.8] for patients with nonenhancing glioma and 3.6 months (95% CI, 1.8–6.5) for patients with enhancing glioma. Exploratory evaluation of tumor volumes in patients with nonenhancing glioma showed sustained tumor shrinkage in multiple patients. Conclusions: Vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing mIDH LGG.

Background Since IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change. Methods Twenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified. Results 3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO. Conclusion 3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less “yo-yo-ing” of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

Imaging response assessment is a cornerstone of patient care and drug development in oncology. Clinicians/clinical researchers rely on tumor imaging to estimate the impact of new treatments and guide decision making for patients and candidate therapies. This is important in brain cancer, where associations between tumor size/growth and emerging neurological deficits are strong. Accurately measuring the impact of a new therapy on tumor growth early in clinical development, where patient numbers are small, would be valuable for decision making regarding late-stage development activation. Current attempts to measure the impact of a new therapy have limited influence on clinical development, as determination of progression, stability or response does not currently account for individual tumor growth kinetics prior to the initiation of experimental therapies. Therefore, we posit that imaging-based response assessment, often used as a tool for estimating clinical effect, is incomplete as it does not adequately account for growth trajectories or biological characteristics of tumors prior to the introduction of an investigational agent. Here, we propose modifications to the existing framework for evaluating imaging assessment in primary brain tumors that will provide a more reliable understanding of treatment effects. Measuring tumor growth trajectories prior to a given intervention may allow us to more confidently conclude whether there is an anti-tumor effect. This updated approach to imaging-based tumor response assessment is intended to improve our ability to select candidate therapies for later-stage development, including those that may not meet currently sought thresholds for “response” and ultimately lead to identification of effective treatments.

Background: The primary outcome was to evaluate whether goal-directed fluid therapy (GDFT) protocol, established on stroke volume variation (SVV) and oxygen delivery index (DO2I) using electrical c...

The current study aimed to identify psychological immunity in the relationship to infection with the corona virus among students of the College of Education at the university and to determine whether there are differences in psychological immunity, due to the gender variables (males-females), and infection with the corona virus (infected-not infected). The study aimed to identify to which extent the infection with the corona virus can be predicted through psychological immunity. The study sample consisted of 120 students of the Faculty of Education, University of Alexandria, 60 males and 60 females. The study used the psychological immunity scale and the response scale to infection with the corona virus prepared by the researcher. The results showed a negative correlation between psychological immunity and its dimensions and between the response to infection with the corona virus and its dimensions.

Horizontal and deviated well architectures are now quite common as they facilitate drainage of reservoir in a cost-effective manner, such architectures introduce a challenging environment for subsequent completions and bottom hole operations performed through Coiled Tubing (CT) mainly due to friction between the coiled tubing string and well casing or reservoir formation rocks. To address this, a variety of techniques have been used over the years to reduce the friction between the metallic surfaces and extend the reach of the coiled tubing string to desired depths. Several Such techniques included-but were not limited to- using a specifically designed CT string (tapered CT strings, Pipe surface smoothing treatments), using mechanical aids (downhole coiled tubing tractors, coiled tubing agitators or vibrators) and increasing lubricity of the annulus fluid through the use of lubricants, there has also been many cases in which multiple techniques have been used at the same time to further extend the CT reach.4 The use of lubricants has always been the easiest technique as it does not require investment into equipment which would increase the complexity of the operation in addition to their cost. In this study, we are evaluating the friction reduction performance of an environmentally friendly surfactant-based metal friction reducer which will be called Lubricant A, the chemistry of Lubricant A has been used before in oilfield applications, but the authors believe this is the first time this chemistry is used for lubricity enhancement. We will be assessing Lubricant A performance at room temperature and 170°F to investigate its thermal stability and we will be evaluating its compatibility with common brines used during CT operations, especially at high concentrations of salt. We will also be comparing the performance of Lubricant A to that of a Co-polymer based Lubricant -which will be labeled Lubricanr B- in terms of Coefficient of Friction (CoF) reduction at room temperature and at 170°F. A core flood test has also been performed to investigate the impact of brines containing Lubricant A on reservoir rocks permeability. Based on our lab testing, Lubricant A manages to drop the coefficient of friction (CoF) by 60-70% in most cases and shows relatively high compatibility with different brines at different salt concentrations, outperforming Lubricant B in most cases. Lubricant A has also shown insignificant reduction in permeability during core flood tests, increasing the potential for its use in operations where formation damage might be a concern.

Background Inhibition of the isocitrate dehydrogenase (IDH)-mutant enzyme is a novel therapeutic target in IDH-mutant gliomas. Imaging biomarkers of IDH inhibitor treatment efficacy in human IDH-mutant gliomas are largely unknown. This study investigated early volumetric, perfusion, and diffusion MRI changes in IDH1-mutant gliomas during IDH inhibitor treatment. Methods Twenty-nine IDH1-mutant glioma patients who received IDH inhibitor and obtained anatomical, perfusion, and diffusion MRI pretreatment at 3–6 weeks (n = 23) and/or 2–4 months (n = 14) of treatment were retrospectively studied. Normalized relative cerebral blood volume (nrCBV), apparent diffusion coefficient (ADC), and fluid-attenuated inversion recovery (FLAIR) hyperintensity volume were analyzed. Results After 3–6 weeks of treatment, nrCBV was significantly increased (P = .004; mean %change = 24.15%) but not FLAIR volume (P = .23; mean %change = 11.05%) or ADC (P = .52; mean %change = -1.77%). Associations between shorter progression-free survival (PFS) with posttreatment nrCBV > 1.55 (P = .05; median PFS, 240 vs 55 days) and increased FLAIR volume > 4 cm3 (P = .06; 227 vs 29 days) trended toward significance. After 2–4 months, nrCBV, FLAIR volume, and ADC were not significantly different from baseline, but an nrCBV increase > 0% (P = .002; 1121 vs 257 days), posttreatment nrCBV > 1.8 (P = .01; 1121 vs. 270 days), posttreatment ADC 0% (P = .02; 1121 vs 270 days), and FLAIR volume change > 4 cm3 (P = .03; 421 vs 226.5 days) were associated with shorter PFS. Conclusions Increased nrCBV at 3–6 weeks of treatment may reflect transient therapeutic and/or tumor growth changes, whereas nrCBV, ADC, and FLAIR volume changes occurring at 2–4 months of treatment may more accurately reflect antitumor response to IDH inhibition.

Background To date, there is limited data on evaluation of the cordotomy lesion and predicting clinical outcome. Objective To evaluate the utility of magnetic resonance (MR)-based radiomic analysis to quantify microstructural changes created by the cordotomy lesion and predict outcome in patients undergoing percutaneous cordotomy for medically refractory cancer pain. Methods This is a retrospective interpretation of prospectively acquired data in 10 patients (5 males, age range 43-76 yr) who underwent percutaneous computed tomography-guided high cervical cordotomy for medically refractory cancer pain between 2015 and 2016. All patients underwent magnetic resonance imaging (MRI) of the cordotomy lesion on postoperative day 1. After segmentation of T2-weighted images, 310 radiomic features were extracted. Pain outcomes were recorded on postoperative day 1 and day 7 using the visual analog scale. R software was used to build statistical models based on MRI radiomic features for prediction of pain outcomes. Results A total of 20 relevant radiomic features were identified using the maximum relevance minimum redundanc method. Radiomics predicted postoperative day 1 pain scores with an accuracy of 90% (P = .046), 100% sensitivity, 75% specificity, 85.7% positive predictive value, and 100% negative predictive value. The radiomics model also predicted if the postoperative day 1 pain score was sustained on postoperative day 7 with an accuracy of 100% (P = .028), 100% sensitivity, 100% specificity, and 100% positive and negative predictive value. Conclusion MR-based radiomic analysis of the cordotomy lesion was predictive of pain outcomes at 1 wk after percutaneous cordotomy for intractable cancer pain.

BACKGROUND Astrocytomas are a subset of diffuse gliomas defined by intact 1p and 19q arms. Isocitrate dehydrogenase 1 mutations (mIDH-1) occur in ~70% of grade 2/3 gliomas, leading to accumulation of 2-hydroxyglutarate (2-HG). Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mIDH1/2 enzymes being investigated in a phase 3 study in non-enhancing gliomas. In an ongoing perioperative study in grade 2/3 gliomas, treatment with VOR was associated with interferon (IFN) signaling activation and increased T-cell infiltration, suggesting adequate 2-HG suppression renders the tumor immune microenvironment for immune checkpoint blockade, and supporting investigation of VOR in combination with an anti-programmed cell death (PD-1) antibody such as pembrolizumab in recurrent IDH-mutant gliomas treatment. This study will evaluate the safety and tolerability of VOR plus pembrolizumab to determine the recommended combination dose (RCD) of VOR, and evaluate CD3+ T-cell infiltration in tumors following preoperative treatment with the combination or VOR. METHODS This study will enroll ~70 patients with recurrent or progressive Grade 2/3 mIDH-1 astrocytoma. Key eligibility: enhancing disease, mIDH1-R132H, Karnofsky Performance Status ≥70, eligible for resection (perioperative phase only). Safety lead-in: Cohort 1 (Nf~6): VOR 40 mg QD plus pembrolizumab 200 mg Q3W in 21-day cycles. Based on DLT evaluation, cohort 2 may enroll an additional ~6 patients at VOR 20 mg QD plus pembrolizumab 200 mg Q3W. Randomized, perioperative phase (Nf~60): randomized 1:1:1 to the combination, VOR 40 mg QD, or untreated for 4 weeks preoperatively; all patients can opt to receive the combination postoperatively. Primary objectives: safety and tolerability, and VOR RCD with pembrolizumab; CD3+ T-cell infiltration in resected tumors following presurgical treatment with the combination compared to untreated tumors. Secondary objectives include clinical activity, VOR PK in tumor and blood, 2-HG concentration in tumors, and overall survival. This study will be active in the United States.

On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.

Pseudoprogression (PsP) is a diagnostic clinical dilemma in cancer. In this study, we retrospectively analyse glioblastoma patients, and using their dynamic susceptibility contrast and dynamic contrast-enhanced perfusion MRI images we build a classifier using radiomic features obtained from both Ktrans and rCBV maps coupled with support vector machines. We achieve an accuracy of 90.82% (area under the curve (AUC) = 89.10%, sensitivity = 91.36%, 67 specificity = 88.24%, p = 0.017) in differentiating between pseudoprogression (PsP) and progressive disease (PD). The diagnostic performances of the models built using radiomic features from Ktrans and rCBV separately were equally high (Ktrans: AUC = 94%, 69 p = 0.012; rCBV: AUC = 89.8%, p = 0.004). Thus, this MR perfusion-based radiomic model demonstrates high accuracy, sensitivity and specificity in discriminating PsP from PD, thus provides a reliable alternative for noninvasive identification of PsP versus PD at the time of clinical/radiologic question. This study also illustrates the successful application of radiomic analysis as an advanced processing step on different MR perfusion maps., MRI scans of glioblastoma patients can be misleading and some patients appear to show features of progressive disease although they respond to treatment. Here, the authors use MRI images of progressive disease or pseudoprogression and build a classifier using machine learning to distinguish the two.

The development of power generators that can function in harsh snowy environments and in contact with snow can be beneficial but challenging to accomplish. Herein, we introduce the first snow-based triboelectric nanogenerator (snow-TENG) that can be used as an energy harvester and a multifunctional sensor based on the principle of snow-triboelectrification. In this work, we used a 3D printing technique for the precise design and deposition of the electrode and triboelectric layer, leading to flexible, stretchable and metal-free triboelectric generators. Based on the single electrode mode, the device can generate an instantaneous output power density as high as 0.2 mW/m(2), an open circuit voltage up to 8 V, and a current density of 40 μA/m(2). In addition, the snow-TENG can function as a miniaturized weather station to monitor the weather in real time to provide accurate information about the snowfall rate, snow accumulation depth, wind direction, and speed in snowy and/or icy environments. In addition, the snow-TENG can be used as a wearable power source and biomechanical sensor to detect human body motions, which may prove useful for snow-related sports. Unlike conventional sensor platforms, our design works without the need for batteries or image processing systems. We envision these devices could potentially be integrated into solar panels to ensure continuous power supply during snowy weather conditions.

The development of highly sensitive sensors and power generators that could function efficiently in extreme temperatures and contact with fire can be lifesaving but challenging to accomplish. Herein, we report, for the first time, a fire-retardant and self-extinguishing triboelectric nanogenerator (FRTENG), which can be utilized as a motion sensor and/or power generator in occupations such as oil drilling, firefighting or working in extreme temperature environments with flammable and combustible materials. The device takes advantage of the excellent thermal properties of carbon derived from resorcinol-formaldehyde aerogel whose electrical, mechanical and triboelectric properties have been improved via the introduction of Polyacrylonitrile nanofibers and graphene oxide nanosheets. This FRTENG is not flammable even after 90 s of trying, whereas conventional triboelectric materials were entirely consumed by fire under the same conditions. The developed device shows exceptional charge transfer characteristics, leading to a potential difference up to 80 V and a current density up to 25 µA/m2. When integrated into firefighter's shoes, the FRTENG is able to discern the movements of a firefighter in hazardous situations, while providing the high thermal stability missing in conventional TENGs. The fire-retardant and self-extinguishing characteristics offered by the FRTENG makes it a path-breaking device for lifesaving wearable applications.

Seizures are commonly thought to occur in a spontaneous, unpredictable manner. However, it is well-established that a subset of patients with epilepsy can experience reflex seizures that are consistently elicited by a specific stimulus. While various forms of reflex epilepsy have been documented in the literature, acute affective states have not been commonly described as a potential reflex seizure trigger. We performed a systematic literature review to determine if acute emotional states can trigger reflex seizures. We included any case in which reflex seizures repeatedly occurred in response to a patient-specific stimulus that was reported as emotionally relevant by the authors. This yielded our case series of ten patients who have been described to have reflex seizures in response to emotional stimuli. We characterized features of these cases including the following: age, gender, developmental and psychiatric history, seizure semiology and duration, emotional triggers, other reflex triggers, relationship between reflex triggers and seizures, investigations, localization, final diagnosis, treatment, and outcome. Considerable variability was found between cases. A trend toward limbic seizure semiology with psychic aura originating in networks involved in emotional processing was noted, with temporal lobe epilepsy being the most common, although without clear laterality or gender predominance. In addition, the report of a significant life stressor occurring at epilepsy onset in three of ten patients as well as the initial suspicion that reflex epileptic seizures were psychogenic in three cases both emphasize the role of electroencephalography in assessment of such presentations to avoid missing a diagnosis of epilepsy. Findings from these ten cases suggest that a patient-specific affective stimulus may trigger reflex seizures in a subset of patients, and that this could be underrecognized or mislabeled as nonepileptic. We encourage future studies with larger numbers to further characterize this phenomenon. Insights gained may enhance our understanding of seizure localization and bear potential treatment implications.

The effect of different concentrations of NaCl (6, 8 and 10 dS/m) on growth and alkaloids production in 21 days-old callus of Egyptian henbane (Hyoscyamu muticus L.) was studied. Results showed that 10 dS/m of NaCl increased fresh and dry weight by 4.1 and 2.8 fold more than control, respectively. Two fold Total alkaloids increased by 2 fold at 10 dS/m compared to control or wild leaves. In contrary, wild leaves had the highest amount of hyosyamine (2.8 mg/g DW) followed by 6 dS/m stressed-callus (1.14 mg/g DW) as detected by HPTLC. Peroxidase and superoxide dismutase activity were increased by 2.6 and 2.3 fold, respectively in highly salt stressed callus than control while catalase activity (CAT) was decreased. Anthocyanin concentration was increased 3 fold in 10 dS/m of NaCl stressed callus compared to control. Glutathione content was increased by 33.8% under low level of NaCl more than control. Reduction of photosynthetic pigments under all NaCl levels led to decrease the total carbohydrate and protein content. Protein band with molecular weight 109 KDa was a unique band in 10dS/m of NaCl treated callus with high expression of protein bands with MW 44, 38 and 32. Histologically, callus cells under high level of NaCl had amoeboid shape and start in senescence with formation of lysiogenous intercellular spaces.

OBJECTIVEDexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug’s impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug’s impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.METHODSExpression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).RESULTSThe mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.CONCLUSIONSThe authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients’ prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

The family in Qatar plays a significant role in shaping its members’ lives, passing down the dominant culture with its history, traditions, values, customs, and social order to subsequent generations. Through the institution of marriage, individuals have been choosing their partners based on criteria passed down to them by their families. They have also been preserving and reproducing the culture, traditions, values, and customs invested in them by their own families by reinvesting them into their own children. By relying on a mixed method approach, the author investigates the role of the family and marriage institutions in the sustenance and stimulation of the reproduction of social stratification in Qatari society. This article is the first of its kind to address the phenomenon of reproduction of social stratification in an Arab state of the Persian Gulf.

Purpose Psychogenic nonepileptic seizures (PNES) are one of the most common differential diagnoses of epilepsy. Our objective is to describe current medical care in Canada and identify patterns of practice and service gaps. Methods In 2015, a 36-question survey was sent via email to the 131 members of the Canadian League Against Epilepsy. The questions were designed after literature review and discussion with the ILAE PNES Task Force. Questions were separated into 5 sections: 1) the role of the respondent and their exposure to PNES, 2) diagnostic methods, 3) management of PNES, 4) etiological factors, and 5) problems accessing health care. Results Sixty-two questionnaires were analyzed (response rate: 47%). Most respondents were epileptologists (76%). The majority of respondents personally diagnosed PNES and communicated the diagnosis to the patient, but only 55% provided follow-up within their practice and only 50% recommended or arranged treatment. Many (35%) were either unfamiliar with the diagnosis of PNES or inexperienced in arranging or offering treatment. Most (79%) provided follow-up to patients with concomitant epilepsy, but when PNES was the sole diagnosis follow-up rates were low. Although 84% of respondents felt that individualized psychological therapy was the most effective treatment, 40% of patients were not referred to psychotherapy and in most cases availability such therapy was low (30–60%). Conclusions Canadian health professionals' understanding of PNES mostly reflects current international expert opinion. Once diagnosis is made however, the majority of patients are discharged from neurological services without appropriate psychological care.

Chapter 8 focuses on the United Arab Emirates (UAE), led by Mohamed bin Zayed, and its newly assertive power projection strategy that includes establishment naval and military bases on the Red Sea, in the chokepoints of the Bab al-Mandab one of the most important global shipping lanes and the Gulf of Aden and its littoral territory—the arid nations of Djibouti, Eritrea, and Somalia to achieve dual geostrategic and economic goals including the acquisition of operational and management rights over ports and economic zones. The theoretical framework used in this chapter to asses foreign policy change employs simultaneous levels of inquiry taking into account regional and systemic effects, domestic influences, and the role of leadership adding to the literature on international relations and the Middle East in two distinct ways (1) by addressing understudied theoretical questions concerning foreign policy change in small states and (2) exploring the nature and motivations of the emerging trend of securitizing waterspace and shipping lanes in the Middle East.