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Fibrolamellar Carcinoma: challenging the challenge
No full textFibrolamellar Carcinoma (FLC) is a rare and poorly-understood malignancy, which seems to be more prevalent in young patients compared to conventional HCC. Performing prospective clinical trials recruiting patients diagnosed with FLC has proven challenging with scarce data available guiding clinical management. The use of a number of chemotherapy compounds in these patients, including cisplatin, epirubicin, 5-fluorouracil (5-FU), and recombinant interferon alpha-2B (IFN-alpha-2B) have been reported in the literature, mainly in the form of case reports. The most promising systemic therapy tested so far is the combination of 5-FU infusion and 3-weekly IFN-alpha-2B, based on results from a phase II clinical trial. This article provides an overview of our own experience with this treatment schedule for patients with FLC, confirming its activity and treatment-derived benefit in the real world. Current challenges being faced by health care professionals treating patients with advanced FLC are discussed, especially the increasingly limited access to IFN-alpha-2B, which could compromise the access to an active therapy in the coming future, and the difficulties in the development of new treatment options for advanced FLC
A Framework for Software Diversification with ISA Heterogeneity
No full textSoftware diversification is one of the most effective ways to defeat memory corruption based attacks. Traditional software diversification such as code randomization techniques diversifies program memory layout and makes it difficult for attackers to pinpoint the precise location of a target vulnerability. Some recent work in the architecture community use diverse ISA configurations to defeat code injection or code reuse attacks, showing that dynamically switching the ISA on which a program executes is a promising direction for future security systems. However, most of these work either remain in a simulation stage or require extra efforts to write program. In this paper, we propose HeterSec, a framework to secure applications utilizing a heterogeneous ISA setup composed of real world machines. HeterSec runs on top of commodity x86_64 and ARM64 machines and gives the process the illusion that it runs on a multi-ISA chip multiprocessor (CMP) machine. With HeterSec, a process can dynamically select its underlying ISA environment. Therefore, a protected process would be capable of hiding the instruction set on which it executed or detecting abnormal program behavior by comparing execution results step-by-step from multiple ISA-diversified instances. To demonstrate the effectiveness of such a software framework, we implemented HeterSec on Linux and showcased its deployability by running it on a pair of x86_64 and ARM64 servers, connected over InfiniBand. We then conducted two case studies with HeterSec. In the first case, we implemented a multi-ISA moving target defense (MTD) system, which introduces uncertainty at the instruction set level. In the second case, we implemented a multi-ISA-based multi-version execution (MVX) system. The evaluation results show that HeterSec brings security benefits through ISA diversification with a reasonable performance overhead
Impact of high tumor mutational burden in solid tumors and challenges for biomarker application
No full textAccurate identification of patients with solid tumors likely to respond to immunotherapy is crucial. Tumor mutational burden (TMB) measures the number of somatic mutations in a tumor and is an emerging prognostic and predictive biomarker for anti-programmed cell death (PD) 1/anti-PD-ligand 1 therapy and other immunotherapeutic agents. Tumor mutational burden is assessed optimally by whole exome sequencing, but next generation sequencing provides TMB estimates in a more timely and cost-effective manner. Blood-based measurement of TMB in plasma offers an alternative to the need for adequate tumor tissue for molecular testing, and has demonstrated the ability to identify patients who derive benefit from immunotherapy. Tumor mutational burden has diverse prognostic impact in different solid tumor types and also has a demonstrated role in predicting improved survival in patients receiving immunotherapy. There are challenges to TMB adoption into standard clinical practice, including variations in its definition, with the mutational number defining TMB-high appearing to vary across cancer types. The magnitude of TMB also varies across different tumor types, with the highest levels reported in melanoma and other skin cancers (where ultraviolet light is the dominant mutational process), followed by non-small cell lung cancer and other squamous carcinomas. Concerns regarding inter-laboratory and inter-platform variations in analysis methods have been raised, highlighting the need for standardization. Integration of other genomic or pathological biomarkers with TMB may increase its prognostic and predictive capabilities and validation of individual or combination models in prospective trials is warranted
Sepsis: Recognition and Management for Nurses
No full textCaring for a patient with suspected sepsis is a challenging nursing role. Earlyrecognition and appropriate management of a patient with sepsis saves lives. Nurses play a fundamental role in detecting changes in physiological observations that could indicate the onset of sepsis. Additionally, an awareness of the pathophysiology of sepsis allows the nurse to better understand how rapid intervention prevents the onset of septic shock. Furthermore, knowledge and use of clinical guidelines and sepsis screening tools are established methods to help reduce patient mortality. Nurse familiarity with ‘Red Flag’ criteria for sepsis and thorough completion of Early Warning Scores (EWS) facilitate earlier recognition and time critical intervention. Delivery of the ‘Sepsis Six’ within one hour of suspected sepsis saves lives
Introduction to Special Issue of Theology and Sexuality: Rethinking Relationships in Cyberspace
No full textLoad balancing routing for wireless mesh network with energy harvesting
No full textCentralized routing is beneficial as it provides a global network view to plan and achieve the best and effective path for real-time traffic. With the rapid development of software defined networking, centralized routing has aroused more and more concern of researchers. An effective centralized load balancing routing (LBR) for wireless mesh network considering energy harvesting is proposed in this letter. LBR can provide flexible and optimal routes for real-time traffic. To minimize the long-term weighted sum cost which includes load and energy condition, LBR considers the queue length, channel condition, energy cost and energy harvesting. The problem of making dynamic decisions based on real-time traffic conditions is solved by the dynamic programming approach. Simulation results demonstrate the advantages of LBR
Giving patients a voice: Implementing patient and public involvement to strengthen research in sub-Saharan Africa
No full textTime-accurate Experimental Investigation of Hypersonic Inlet Buzz at Mach 5
No full textHypersonic inlet buzz is investigated experimentally in a ramjet intake at Mach 5. A twodimensional planar inlet featuring a double-compression ramp with 10° and 22° inclination to the freestream direction and a rectangular cross section duct is tested. A solenoid is used to raise a barrier into the flow and initiate buzz at high throttling ratios. Static pressure is measured at a data sample rate of 10 kHz and Schlieren images are collected at an image frame rate of 30 kHz. Oscillations in the flow not linked to buzz are present both at zero and full throttle and they cause a high-amplitude pressure peak at very high frequency (higher than 3 kHz). At full throttle, buzz is spotted, in the contemporary presence of shear layers being ingested by the intake (Ferri criterion) and of separated flow lying on the second compression ramp (Dailey criterion). Both features are analyzed by means of the standard deviation of the frames captured. The kind of buzz hereby observed activates highamplitude pressure oscillations both at low frequencies and high frequencies. The unstarted flow field is largely subsonic inside the intake and allows for the use of linear acoustic theory. Indeed, one of the peaks recorded matches the quarter-wave resonator frequency (1411 Hz) of the inlet, suggesting that the barrier acts as a solid wall and that the inlet model behaves as a duct with a closed end
English language and language-free detection of spatial processing disorders in Aboriginal and Torres Strait Islander children
No full textObjective: The aim of this study was to compare speech reception thresholds in noise measured with the Listening in Spatialized Noise – Universal test (LiSN-U; which requires no English knowledge) with those measured from the relevant conditions of the LiSN – Sentences test (LiSN-S; a test requiring knowledge of English) in Aboriginal and Torres Strait Islander children. A second aim was to compare the ability of the two tests to detect spatial processing disorder. Design: Participants completed audiometry, the LiSN-S, and the LiSN-U.Study Sample: 90 Aboriginal and Torres Strait Islander children aged six to 14 years tested in a school setting.Results: Strong correlations were found between speech reception thresholds in noise for the two tests. A moderate correlation was found between the difference scores that each test uses to detect spatial processing disorder. Consistent diagnoses of whether a child had spatial processing disorder or not on both tests were found for 72% of children.Conclusions: The moderate-to-strong relationships and agreement between diagnoses found for the LiSN-S and LiSN-U show promise for the LiSN-U being used as a tool to investigate spatial processing disorder in children, without requiring the test to use a language familiar to the children being tested. <br/
Signature of Geochemistry on Density-Driven CO2 Mixing in 1 Sandstone Aquifers
No full textDensity-driven mixing resulting from CO2 injection into aquifers leads to the CO2 entrapment mechanism of solubility trapping. Crucially the coupled flow-geochemistry and effects of geochemistry on density-driven mixing process for “sandstone rocks” have not been adequately addressed. Often there are conflicting remarks in the literature as to whether geochemistry promotes or undermines dissolution-driven convection in sandstone aquifers. Against this backdrop, we simulate density driven mixing in sandstone aquifers by developing a 2D modified stream function formulation formulticomponent reactive convective-diffusive CO2 mixing. Two different cases corresponding to laboratory and field scales are studied to investigate the effect of rock-fluid interaction on density driven mixing and the role of mineralization in carbon storage over the project life time. A complex sandstone mineralogical assemblage is considered and solid-phase reactions are assumed to be kinetic to study the length- and time-scale dependency of the geochemistry effects. The study revealed nonuniform impact of rock-fluid and fluid-fluid interaction in early- and late-time stages of the process. The results show that for moderate Rayleigh (Ra) numbers, rock-fluid interactions adversely affect solubility trapping while improving the total carbon captured through mineral trapping. Simulation results in the range of 1,500 < Ra < 55,000 in the field-scale model, showed more pronounced impact of geochemistry for higher Ra numbers, as geochemistry stimulates the convective instabilities and improves the total sequestered carbon. This study gives new insights into the effect of rock-fluid interactions on density driven mixing and solubility trapping in sandstone aquifers to improve estimation of the carbon storage capacity in deep saline aquifers