DMAC: Deadline-Miss-Aware Control

The real-time implementation of periodic controllers requires solving a co-design problem, in which the choice of the controller sampling period is a crucial element. Classic design techniques limit the period exploration to safe values, that guarantee the correct execution of the controller alongside the remaining real-time load, i.e., ensuring that the controller worst-case response time does not exceed its deadline. This paper presents DMAC: the first formally-grounded controller design strategy that explores shorter periods, thus explicitly taking into account the possibility of missing deadlines. The design leverages information about the probability that specific sub-sequences of deadline misses are experienced. The result is a fixed controller that on average works as the ideal clairvoyant time-varying controller that knows future deadline hits and misses. We obtain a safe estimate of the hit and miss events using the scenario theory, that allows us to provide probabilistic guarantees. The paper analyzes controllers implemented using the Logical Execution Time paradigm and three different strategies to handle deadline miss events: killing the job, letting the job continue but skipping the next activation, and letting the job continue using a limited queue of jobs. Experimental results show that our design proposal - i.e., exploring the space where deadlines can be missed and handled with different strategies - greatly outperforms classical control design techniques

Beyond the Weakly Hard Model: Measuring the Performance Cost of Deadline Misses (Artifact)

This document provides a brief description of the artifact material related to the paper "Beyond the Weakly Hard Model: Measuring the Performance Cost of Deadline Misses". The code provided in the artifact implements the algorithms presented in the paper and all the experimental tests

Beyond the Weakly Hard Model: Measuring the Performance Cost of Deadline Misses

Most works in schedulability analysis theory are based on the assumption that constraints on the performance of the application can be expressed by a very limited set of timing constraints (often simply hard deadlines) on a task model. This model is insufficient to represent a large number of systems in which deadlines can be missed, or in which late task responses affect the performance, but not the correctness of the application. For systems with a possible temporary overload, models like the m-K deadline have been proposed in the past. However, the m-K model has several limitations since it does not consider the state of the system and is largely unaware of the way in which the performance is affected by deadline misses (except for critical failures). In this paper, we present a state-based representation of the evolution of a system with respect to each deadline hit or miss event. Our representation is much more general (while hopefully concise enough) to represent the evolution in time of the performance of time-sensitive systems with possible time overloads. We provide the theoretical foundations for our model and also show an application to a simple system to give examples of the state representations and their use

Relationship between spatial ability, visuospatial working memory and self-assessed spatial orientation ability: a study in older adults

This paper describes some novel spatial tasks and questionnaires designed to assess spatial and orientation abilities. The new tasks and questionnaires were administered to a sample of 90 older adults (41 males, age range 57–90), along with some other tests of spatial ability (Minnesota Paper Form Board, Mental Rotations Test, and Embedded Figures Test) and tests of visuospatial working memory (Corsi’s Block Test and Visual Pattern Test). The internal reliability of the new tasks and questionnaires was analyzed, as well as their relationship with the spatial and working memory tests. The results showed that the new spatial tasks are reliable, correlate with working memory and spatial ability tests and, compared with the latters, show stronger correlations with the self-report questionnaires referring to orientation abilities. A model was also tested (with reference to Allen et al. in Intelligence 22:327–355, 1996) in which the new tasks were assumed to relate to spatial ability and predict orientation abilities as assessed by the self-report measures

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study

Introduction: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF). Methods: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value 46% at discharge had an area under curve (AUC) of 0.70 (P 300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P 46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P 300 pg/mL and whose percentage decrease at discharge was 46% was 9.614 (CI 4.51 - 20.47, P 46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP.

The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy in childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), a key regulator of innate and adaptive antitumor immune responses, as a previously unknown player in the Hh signaling pathway. We demonstrate that ERAP1 binds the deubiquitylase enzyme USP47, displaces the USP47-associated βTrCP, the substrate-receptor subunit of the SCFβTrCP ubiquitin ligase, and promotes βTrCP degradation. These events result in the modulation of Gli transcription factors, the final effectors of the Hh pathway, and the enhancement of Hh activity. Remarkably, genetic or pharmacological inhibition of ERAP1 suppresses Hh-dependent tumor growth in vitro and in vivo. Our findings unveil an unexpected role for ERAP1 in cancer and indicate ERAP1 as a promising therapeutic target for Hh-driven tumors

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking.</p> <p>Objectives</p> <p>To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT.</p> <p>Methods/Design</p> <p>Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled.</p> <p>Discussion</p> <p>The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01257672">NCT01257672</a></p