Management of exercise-induced glycaemic imbalances in type 1 diabetes

Regular moderate-intensity exercise is strongly recommended for its beneficial effects in all people. In patients with type 1 diabetes, however, the exercise-associated glycemic imbalances remain an unresolved clinical challenge. Current guidelines require an in-depth understanding of the glycemic responses to exercise and each patient has to discover, by trial-and-error, his/her own strategy, several attempts being usually required to gain sufficient experience. Consequently, fear of hypoglycemia remains the strongest barrier to physical activity. This paper explores the potential strategies that may be employed to minimize the risk of exercise related glycemic imbalances. Moreover, a newly developed algorithm (ECRES, Exercise Carbohydrate Requirement Estimating Software) is described, which estimates on a patient-and situation-specific basis the glucose supplement required by the patient to maintain safe blood glucose levels. The algorithm was tested on 27 patients who performed three 1-hr constant intensity walks (each starting at a different time interval following insulin injection). Results showed that in 70.4% of the trials, independent of the time of day, the algorithm provided a satisfactory estimate of the carbohydrates needed by patients to complete the exercise with a glucose level within safe thresholds (i.e. 3.9 - 10 mmol\ub7L -1). Despite the algorithm requires further experimental testing to be applied by the majority of patients, these results indicate its potential usefulness as a tool for preventing immediate exercise-induced glycemic imbalances (i.e. during exercise) in type 1 diabetic patients, in particular for spontaneous activities not planned in advance, thus allowing all insulin-dependent patients to safely enjoy the benefits of exercise

A Survey on FPGA-Based Heterogeneous Clusters Architectures

In recent years, the most powerful supercomputers have already reached megawatt power consumption levels, an important issue that challenges sustainability and shows the impossibility of maintaining this trend. To this date, the prevalent approach to supercomputing is dominated by CPUs and GPUs. Given their fixed architectures with generic instruction sets, they have been favored with lots of tools and mature workflows which led to mass adoption and further growth. However, reconfigurable hardware such as FPGAs has repeatedly proven that it offers substantial advantages over this supercomputing approach concerning performance and power consumption. In this survey, we review the most relevant works that advanced the field of heterogeneous supercomputing using FPGAs focusing on their architectural characteristics. Each work was divided into three main parts: network, hardware, and software tools. All implementations face challenges that involve all three parts. These dependencies result in compromises that designers must take into account. The advantages and limitations of each approach are discussed and compared in detail. The classification and study of the architectures illustrate the trade-offs of the solutions and help identify open problems and research lines

Automatic Differentiation for Inverse Problems in X-ray Imaging and Microscopy

Computational techniques allow breaking the limits of traditional imaging methods, such as time restrictions, resolution, and optics flaws. While simple computational methods can be enough for highly controlled microscope setups or just for previews, an increased level of complexity is instead required for advanced setups, acquisition modalities or where uncertainty is high; the need for complex computational methods clashes with rapid design and execution. In all these cases, Automatic Differentiation, one of the subtopics of Artificial Intelligence, may offer a functional solution, but only if a GPU implementation is available. In this paper, we show how a framework built to solve just one optimisation problem can be employed for many different X-ray imaging inverse problems

Cyclooxygenase-2 Expression in Bladder Cancer and Patient Prognosis: Results from a Large Clinical Cohort and Meta-Analysis

Aberrant overexpression of cyclooxygenase-2 (COX2) is observed in urothelial carcinoma of the bladder (UCB). Studies evaluating COX2 as a prognostic marker in UCB report contradictory results. We determined the prognostic potential of COX2 expression in UCB and quantitatively summarize the results with those of the literature through a meta-analysis. Newly diagnosed UCB patients recruited between 1998–2001 in 18 Spanish hospitals were prospectively included in the study and followed-up (median, 70.7 months). Diagnostic slides were reviewed and uniformly classified by expert pathologists. Clinical data was retrieved from hospital charts. Tissue microarrays containing non-muscle invasive (n = 557) and muscle invasive (n = 216) tumours were analyzed by immunohistochemistry using quantitative image analysis. Expression was evaluated in Cox regression models to assess the risk of recurrence, progression and disease-specific mortality. Meta-hazard ratios were estimated using our results and those from 11 additional evaluable studies. COX2 expression was observed in 38% (211/557) of non-muscle invasive and 63% (137/216) of muscle invasive tumors. Expression was associated with advanced pathological stage and grade (p<0.0001). In the univariable analyses, COX2 expression - as a categorical variable - was not associated with any of the outcomes analyzed. As a continuous variable, a weak association with recurrence in non-muscle invasive tumors was observed (p-value = 0.048). In the multivariable analyses, COX2 expression did not independently predict any of the considered outcomes. The meta-analysis confirmed these results. We did not find evidence that COX2 expression is an independent prognostic marker of recurrence, progression or survival in patients with UCB.The work was partially supported by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain (G03/174, 00/0745, PI051436, PI061614 and G03/174); Red Temática de Investigación Cooperativa en Cáncer- RD06/0020-RTICC; Consolider ONCOBIO; EU-FP6-STREP-37739-DRoP-ToP; EU-FP7-HEALTH-F2-2008-201663-UROMOL; EU-FP7-HEALTH-F2-2008-201333-DECanBio; USA-NIH-RO1-CA089715; and a PhD fellowship awarded to MJC from the ‘‘la Caixa’’ foundation, Spain, and a postdoctoral fellowship awarded to AFSA from the Fundación Científica de la AEC

Gamma/neutron classification with SiPM CLYC detectors using frequency-domain analysis for embedded real-time applications

A method for gamma/neutron event classification based on frequency-domain analysis for mixed radiation environments is proposed. In contrast to the traditional charge comparison method for pulse-shape discrimination, which requires baseline removal and pulse alignment, our method does not need any preprocessing of the digitized data, apart from removing saturated traces in sporadic pile-up scenarios. It also features the identification of neutron events in the detector’s full energy range with a single device, from thermal neutrons to fast neutrons, including low-energy pulses, and still provides a superior figure-of-merit for classification. The proposed frequency-domain analysis consists of computing the fast Fourier transform of a triggered trace and integrating it through a simplified version of the transform magnitude components that distinguish the neutron features from those of the gamma photons. Owing to this simplification, the proposed method may be easily ported to a real-time embedded deployment based on Field-Programmable Gate Arrays or Digital Signal Processors. We target an off-the-shelf detector based on a small CLYC (Cs2LiYCl6:Ce) crystal coupled to a silicon photomultiplier with an integrated bias and preamplifier, aiming at lightweight embedded mixed radiation monitors and dosimeter applications

A label free disposable device for rapid isolation of rare tumor cells from blood by ultrasounds

The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties in a label-free, contactless and biocompatible manner. Herein, we describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs) from white blood cells (WBCs) in a microfluidic device, "THINUS-Chip" (Thin-Ultrasonic-Separator-Chip), actuated by ultrasounds. We introduce for the first time the concept of plate acoustic waves (PAW) applied to acoustophoresis as a new strategy. It lies in the geometrical chip design: different to other microseparators based on either bulk acoustic waves (BAW) or surface waves (SAW, SSAW and tSAW), it allows the use of polymeric materials without restrictions in the frequency of work. We demonstrate its ability to perform high-throughput isolation of TCs from WBCs, allowing a recovery rate of 84%±8% of TCs with a purity higher than 80% and combined viability of 85% at a flow rate of 80 µL/min (4.8 mL/h). The THINUS-Chip performs cell fractionation with low-cost manufacturing processes, opening the door to possible easy printing fabrication

Development and tests of a new prototype detector for the XAFS beamline at Elettra Synchrotron in Trieste

The XAFS beamline at Elettra Synchrotron in Trieste combines X-ray absorption spectroscopy and X-ray diffraction to provide chemically specific structural information of materials. It operates in the energy range 2.4-27 keV by using a silicon double reflection Bragg monochromator. The fluorescence measurement is performed in place of the absorption spectroscopy when the sample transparency is too low for transmission measurements or the element to study is too diluted in the sample. We report on the development and on the preliminary tests of a new prototype detector based on Silicon Drift Detectors technology and the SIRIO ultra low noise front-end ASIC. The new system will be able to reduce drastically the time needed to perform fluorescence measurements, while keeping a short dead time and maintaining an adequate energy resolution to perform spectroscopy. The custom-made silicon sensor and the electronics are designed specifically for the beamline requirements.Comment: Proceeding of the 6YRM 12th-14th Oct 2015 - L'Aquila (Italy). Accepted for publication on Journal of Physics: Conference Serie

Understanding Needs, Identifying Opportunities: ICT in the View of Universal Design

This article provides food for thoughts elaborated by peer researchers who, basing on their studies and on current literature on relationships between Universal Design (UD) and Information and Communication Technologies (ICT), wish to share few key issues related to the challenges offered by the involvement of final users in designing product and services. Referring to approaches from different disciplines, key questions will be highlighted on which a debate could start, focused on the issue of promoting inclusion and how a close relationship among these different areas of knowledge can contribute to bridge the gap between the potential of new technologies and the real and diversified need by persons. Thus, actively contributing toward the empowerment of the community of belonging

A scalable High Voltage Power Supply System with system on chip control for Micro Pattern Gaseous Detectors

The requirements posed to high voltage power supply systems by the operation of Micro Pattern Gaseous Detectors are specific in terms of high resolution diagnostic features and intelligent dynamic voltage control. These requirements are needed both when technology development is performed and when extended detector systems are supplied and monitored. Systems satisfying all the needed features are not commercially available. A single channel high voltage system matching the Micro Pattern Gaseous Detector needs has been designed and realized, including its hardware and software components. The system employs a commercial DCDC converter and is coupled to a custom high resolution ammeter. Local intelligence, flexibility and high speed inter-connectivity are provided by a System on Chip Board and the use of a powerful FPGA. The single channel system has been developed, as critical milestone towards the realization of a multi-channel system. The design, implementation and performance of the system are reported in detail in this article, as well as the performance of the single channel power supply when connected to a Micro Pattern Gaseous Detector in realistic working condition during a test beam exercise

ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity

Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness