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

Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells

The contribution of cell-extrinsic factors in Acute Myeloid Leukemia (AML) generation and persistence has gained interest. Bitter taste receptors (TAS2Rs) are G protein-coupled receptors known for their primary role as a central warning signal to induce aversion toward noxious or harmful substances. Nevertheless, the increasing amount of evidence about their extra-oral localization has suggested a wider function in sensing microenvironment, also in cancer settings. In this study, we found that AML cells express functional TAS2Rs. We also highlighted a significant association between the modulation of some TAS2Rs and the poor-prognosis AML groups, i.e., TP53- and TET2-mutated, supporting a potential role of TAS2Rs in AML cell biology. Gene expression profile analysis showed that TAS2R activation with the prototypical agonist, denatonium benzoate, significantly modulated a number of genes involved in relevant AML cellular processes. Functional assay substantiated molecular data and indicated that denatonium reduced AML cell proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation. Moreover, denatonium exposure impaired AML cell motility and migratory capacity, and inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation. In conclusion, our results in AML cells expand the observation of cancer TAS2R expression to the setting of hematological neoplasms and shed light on a role of TAS2Rs in the extrinsic regulation of leukemia cell functions

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

Characterizing the Effect of Deadline Misses on Time-Triggered Task Chains

Modern embedded software includes complex functionalities and routines, often implemented by splitting the code across different tasks. Such tasks communicate their partial computations to their successors, forming a task chain. Traditionally, this architecture relies on the assumption of hard deadlines and timely communication. However, in actual implementations, tasks may miss their deadlines, thus affecting the propagation of their data. This article analyzes a task chain in which tasks can fail to complete their jobs according to the weakly-hard task model. We explore how missing deadlines affect chains in terms of classic latency metrics and valid data paths. Our analysis, based on mixed integer linear programming, extracts the worst-case deadline miss pattern for any given performance metric

Stability of Control Systems under Extended Weakly-Hard Constraints

14 pages, 2 figures, 2 tablesControl systems can show robustness to many events, like disturbances and model inaccuracies. It is natural to speculate that they are also robust to alterations of the control signal pattern, due to sporadic late completions (called deadline misses) when implemented as a digital task on an embedded platform. Recent research analysed stability when imposing constraints on the maximum number of consecutive deadlines that can be missed. This is only one type of characterization, and results in a pessimistic analysis when applied to more general cases. To overcome this limitation, this paper proposes a comprehensive stability analysis for control systems subject to a set of generic constraints, describing the possible sequences of correct completions and deadline misses. The proposed analysis brings the assessment of control systems robustness to computational problems one step closer to the controller implementation

Stability of Linear Systems under Extended Weakly-Hard Constraints

Control systems can show robustness to many events, like disturbances and model inaccuracies. It is natural to speculate that they are also robust to sporadic deadline misses when implemented as digital tasks on an embedded platform. This paper proposes a comprehensive stability analysis for control systems subject to deadline misses, leveraging a new formulation to describe the patterns experienced by the control task under different handling strategies. Such analysis brings the assessment of control systems robustness to computational problems one step closer to the controller implementation

Pilomatrix carcinoma of the nose: Clinical and dermoscopic presentationKey message

open6no.openRavaioli, Giulia Maria; Lambertini, Martina*; Pazzaglia, Massimiliano; Corti, Barbara; Fanti, Pier Alessandro; Dika, EmiRavaioli, Giulia Maria; Lambertini, Martina*; Pazzaglia, Massimiliano; Corti, Barbara; Fanti, Pier Alessandro; Dika, Em

Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas

Background. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis

Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.

The contribution of cell-extrinsic factors in Acute Myeloid Leukemia (AML) generation and persistence has gained interest. Bitter taste receptors (TAS2Rs) are G protein-coupled receptors known for their primary role as a central warning signal to induce aversion toward noxious or harmful substances. Nevertheless, the increasing amount of evidence about their extra-oral localization has suggested a wider function in sensing microenvironment, also in cancer settings. In this study, we found that AML cells express functional TAS2Rs. We also highlighted a significant association between the modulation of some TAS2Rs and the poor-prognosis AML groups, i.e., TP53- and TET2-mutated, supporting a potential role of TAS2Rs in AML cell biology. Gene expression profile analysis showed that TAS2R activation with the prototypical agonist, denatonium benzoate, significantly modulated a number of genes involved in relevant AML cellular processes. Functional assay substantiated molecular data and indicated that denatonium reduced AML cell proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation. Moreover, denatonium exposure impaired AML cell motility and migratory capacity, and inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation. In conclusion, our results in AML cells expand the observation of cancer TAS2R expression to the setting of hematological neoplasms and shed light on a role of TAS2Rs in the extrinsic regulation of leukemia cell functions.: This research was supported by: Bologna AIL (Associazione Italiana contro le Leucemie)/Bologna Brancch, FATRO/Foundation Corrado and Bruno Maria Zaini-Bologna, Fabbri1905, Regione Emilia-Romagna and University of Bologna (Young Researcher's fund of the Regione Emilia Romagna, Bando Alessandro Liberati GREREMAT-Curti to AC), Italian Association for Cancer Research grant (AIRC) IG20109 to FB. VS and MC were supported by the American Society of Haematology (ASH)/Giuseppe Bigi Memorial Award and by the University of Bologna (Alma Idea Junior Grant 2017), EA was supported by AIRC IG16812. DF was supported by AIRC fellowship for abroad-2017, Società Italiana di Ematologia (SIE) and Associazione Amici di Beat Leukemia Dr. Alessandro Cevenini ONLUSS