This study was aimed at investigating the intersegmental coordination of six older adults while managing unexpected slippages delivered during steady walking, and wearing an Active Pelvis Orthosis ...(APO). The APO was setup either to assist volunteers at the hip levels during balance loss or to be transparent. The Planar Covariation Law (PCL) of the lower limb elevation angles was the main tool used to assess the intersegmental coordination of both limbs (i.e., the perturbed and unperturbed ones). Results revealed that, after the onset of the perturbation, elevation angles of both limbs do not covary, a part from the robot-mediated assistance. These new evidences suggest that external sensory-motor cues can alter the temporal synchronization of elevation angles, thus violating the PCL.
Purpose:
This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy.
Methods:
CNAO ...Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real‐time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery.
Results:
The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity.
Conclusions:
The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.
The evolution to bipedalism forced humans to develop suitable strategies for dynamically controlling their balance, ensuring stability, and preventing falling. The natural aging process and traumatic ...events such as lower-limb loss can alter the human ability to control stability significantly increasing the risk of fall and reducing the overall autonomy. Accordingly, there is an urgent need, from both end-users and society, for novel solutions that can counteract the lack of balance, thus preventing falls among older and fragile citizens. In this study, we show a novel ecological approach relying on a wearable robotic device (the Active Pelvis Orthosis, APO) aimed at facilitating balance recovery after unexpected slippages. Specifically, if the APO detects signs of balance loss, then it supplies counteracting torques at the hips to assist balance recovery. Experimental tests conducted on eight elderly persons and two transfemoral amputees revealed that stability against falls improved due to the "assisting when needed" behavior of the APO. Interestingly, our approach required a very limited personalization for each subject, and this makes it promising for real-life applications. Our findings demonstrate the potential of closed-loop controlled wearable robots to assist elderly and disabled subjects and to improve their quality of life.
Summary
Background
Several studies have shown that weight changes are common in patients with coeliac disease after starting a gluten‐free diet (GFD), but data on the prevalence of metabolic syndrome ...in this population are still scarce.
Aims
To assess the prevalence of metabolic syndrome in patients with CD at diagnosis and 1 year after starting GFD.
Methods
We enrolled all consecutive patients with newly diagnosed coeliac disease (CD) who were referred to our third‐level CD Unit. For all patients we collected: waist circumference, BMI, blood pressure, lipid profile (HDL cholesterol, triglycerides) and levels of blood glucose. Diagnosis of metabolic syndrome was made according to the International Diabetes Federation (IDF) criteria for European countries. The prevalence of metabolic syndrome was re‐assessed after 12 months of GFD.
Results
Ninety‐eight patients with CD were assessed, two patients with CD (2%) fulfilled the diagnostic criteria for metabolic syndrome at diagnosis and 29 patients (29.5%) after 12 months of GFD (P < 0.01; OR: 20). With regard to metabolic syndrome sub‐categories 1 year after GFD compared to baseline respectively: 72 vs. 48 patients exceeded waist circumference cut‐off (P < 0.01; OR: 2.8); 18 vs. 4 patients had high blood pressure (P < 0.01; OR: 5.2); 25 vs. 7 patients exceeded glycemic threshold (P = 0.01; OR: 4.4); 34 vs. 32 patients with CD had reduced levels of HDL cholesterol (P = 0.7); and 16 vs. 7 patients had high levels of triglycerides (P = 0.05).
Conclusions
Patients with coeliac disease show a high risk of metabolic syndrome 1 year after starting a gluten‐free diet. We suggest that an in‐depth nutritional assessment is undertaken for all patients with coeliac disease.
The R package
for simulating and fitting semi-parametric shared frailty models is introduced. Package
implements semi-parametric consistent estimators for a variety of frailty distributions, ...including gamma, log-normal, inverse Gaussian and power variance function, and provides consistent estimators of the standard errors of the parameters' estimators. The parameters' estimators are asymptotically normally distributed, and therefore statistical inference based on the results of this package, such as hypothesis testing and confidence intervals, can be performed using the normal distribution. Extensive simulations demonstrate the flexibility and correct implementation of the estimator. Two case studies performed with publicly available datasets demonstrate applicability of the package. In the Diabetic Retinopathy Study, the onset of blindness is clustered by patient, and in a large hard drive failure dataset, failure times are thought to be clustered by the hard drive manufacturer and model.
In this paper we report on the timing resolution obtained in a beam test with pions of 180 GeV/c momentum at CERN for the first production of 45 μm thick Ultra-Fast Silicon Detectors (UFSD). UFSD are ...based on the Low- Gain Avalanche Detector (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test had a pad area of 1.7 mm2. The gain was measured to vary between 5 and 70 depending on the sensor bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution was determined by doing Gaussian fits to the time-of-flight of the particles between one or more UFSD and the trigger counter. For a single UFSD the resolution was measured to be 34 ps for a bias voltage of 200 V, and 27 ps for a bias voltage of 230 V. For the combination of 3 UFSD the timing resolution was 20 ps for a bias voltage of 200 V, and 16 ps for a bias voltage of 230 V.
Background
Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA ...methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls.
Methods
Peripheral blood mononuclear cells were obtained from children aged 4‐18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next‐generation sequencing‐based approach. Functional assessment of IL‐4 expression was also performed.
Results
Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR‐193a‐5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR‐193a‐5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a‐5 inhibitor showed a significant upregulation of IL‐4 mRNA and its protein expression. Children who outgrew CMA showed miRNA‐193a‐5p level, and its related targets expression, similar to that observed in healthy controls.
Conclusions
Our results suggest that miR‐193a‐5p is a post‐transcriptional regulator of IL‐4 expression and could have a role in IgE‐mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.
The proof of concept of a new device, capable of determining in a few seconds the energy of clinical proton beams by measuring the time of flight (ToF) of protons, is presented. The prototype ...consists of two thin ultra fast silicon detector (UFSD) pads, aligned along the beam direction in a telescope configuration and readout by a digitizer. The method developed for extracting the energy at the isocenter from the measured ToF, validated by Monte Carlo simulations, and the procedure used to calibrate the system are also presented and discussed in detail. The prototype was tested at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy), at several beam energies, covering the entire clinical range, and using different distances between the sensors. The measured beam energies were benchmarked against the nominal CNAO energy values, obtained during the commissioning of the centre from the measured ranges in water. Deviations of few hundreds of keV have been achieved for all considered proton beam energies for distances between the two sensors larger than 60 cm, indicating a sensitivity to the corresponding beam range in water smaller than the clinical tolerance of 1 mm. Moreover, few seconds of irradiation were necessary to collect the required statistics. These preliminary results indicate that a telescope of UFSDs could achieve in a short time the accuracy required for the clinical application and therefore encourage further investigations towards the improvement and the optimization of the present prototype.
The DC-coupled resistive silicon detectors (DC-RSD) are the evolution of the AC-coupled RSD (RSD) design, both based on the low-gain avalanche diode (LGAD) technology. The DC-RSD design concept ...intends to address a few known issues present in RSDs (e.g., baseline fluctuation and long tail-bipolar signals) while maintaining their advantages (e.g., signal spreading and 100% fill factor). The simulation of DC-RSD presents several unique challenges linked to the complex nature of its design and the large pixel size. The defining feature of DC-RSD, charge sharing over distances that can be as large as a millimeter, represents a formidable challenge for technology CAD (TCAD), the standard simulation tool. To circumvent this problem, we have developed a mixed-mode approach to the DC-RSD simulation, which exploits a combination of two simulation tools: TCAD and SPICE. Thanks to this hybrid approach, it has been possible to demonstrate that, according to the simulation, the key features of the RSD-excellent timing and spatial resolutions (few tens of picoseconds and few microns)-are maintained in the DC-RSD design. In this work, we present the developed models and methodology, mainly showing the results of device-level numerical simulation, which have been obtained with the state-of-the-art Synopsys Sentaurus TCAD suite of tools. Such results will provide all the necessary information for the first batch of DC-RSD produced by the Fondazione Bruno Kessler (FBK) foundry in Trento, Italy.
This study investigates the effectiveness of a robot-mediated strategy aimed at promoting balance recovery after multidirectional slippages. Six older adults were asked to manage anteroposterior and ...mediolateral slippages while donning an active pelvis orthosis (APO). The APO was set up either to assist volunteers during balance loss or to be transparent. The margin of stability, in sagittal and frontal planes, was the main metric to assess the effectiveness of balance recovery. Results showed that the assistive strategy is effective at promoting balance recovery in the sagittal plane, for both perturbing paradigms; however, it is not effective at controlling stability in the frontal plane.
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