Frailty, Disability and Physical Exercise in the Aging Process and in Chronic Kidney Disease

Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD) is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role

DenRAM: Neuromorphic Dendritic Architecture with RRAM for Efficient Temporal Processing with Delays

An increasing number of neuroscience studies are highlighting the importance of spatial dendritic branching in pyramidal neurons in the brain for supporting non-linear computation through localized synaptic integration. In particular, dendritic branches play a key role in temporal signal processing and feature detection, using coincidence detection (CD) mechanisms, made possible by the presence of synaptic delays that align temporally disparate inputs for effective integration. Computational studies on spiking neural networks further highlight the significance of delays for CD operations, enabling spatio-temporal pattern recognition within feed-forward neural networks without the need for recurrent architectures. In this work, we present DenRAM, the first realization of a spiking neural network with analog dendritic circuits, integrated into a 130nm technology node coupled with resistive memory (RRAM) technology. DenRAM's dendritic circuits use the RRAM devices to implement both delays and synaptic weights in the network. By configuring the RRAM devices to reproduce bio-realistic timescales, and through exploiting their heterogeneity, we experimentally demonstrate DenRAM's capability to replicate synaptic delay profiles, and efficiently implement CD for spatio-temporal pattern recognition. To validate the architecture, we conduct comprehensive system-level simulations on two representative temporal benchmarks, highlighting DenRAM's resilience to analog hardware noise, and its superior accuracy compared to recurrent architectures with an equivalent number of parameters. DenRAM not only brings rich temporal processing capabilities to neuromorphic architectures, but also reduces the memory footprint of edge devices, provides high accuracy on temporal benchmarks, and represents a significant step-forward in low-power real-time signal processing technologies

Total Skin Electron Therapy Stanford Technique Evolution With Monte Carlo Simulation Toward Personalized Treatments For Cutaneous Lymphoma

Current Total Skin Electron Therapy (TSET) Stanford technique for cutaneous lymphoma, established in the 70's, involves a unique irradiation setup, i.e. patient's position and beam arrangement, for all patients with ensuing great variability in dose distribution and difficult dose optimization. A Geant4-based simulation has been developed to explore the possibility of personalizing the dose to each patient's anatomy. To achieve this optimization of the treatment method, this project enrolls different aspects of the clinical and computational techniques: starting with the knowledge of the experimental parameters involving TSET practice, passing through an innovative approach to model the patient's anatomy, a precise description of the electron beam and a validated configuration of the physics models handling the interactions of the electrons and of secondary particles. The Geant4-based simulation models the patient as a tessellated solid derived from the optical scan of her/his body, realistically reproduces the irradiation environment in detail and calculates the energy deposition corresponding to each facet of the patient's scanned surface. The resulting three-dimensional dose distribution constitutes the basis for the personalization of the medical treatement as appropriate to each patient's specific characteristics.Comment: Presented at the 2022 IEEE Nuclear Science Symposiu

Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p