306 research outputs found

    Deep Learning for the Generation of Heuristics in Answer Set Programming: A Case Study of Graph Coloring

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    Answer Set Programming (ASP) is a well-established declarative AI formalism for knowledge representation and reasoning. ASP systems were successfully applied to both industrial and academic problems. Nonetheless, their performance can be improved by embedding domain-specific heuristics into their solving process. However, the development of domain-specific heuristics often requires both a deep knowledge of the domain at hand and a good understanding of the fundamental working principles of the ASP solvers. In this paper, we investigate the use of deep learning techniques to automatically generate domain-specific heuristics for ASP solvers targeting the well-known graph coloring problem. Empirical results show that the idea is promising: the performance of the ASP solver wasp can be improved

    The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

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    Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours

    Development of light and highly radiation transparent cryostats for FCC detector magnets:First analyses of insulation materials

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    For both versions of the Future Circular Collider, the electron-positron FCC ee+^+, requiring a 2 T/4 m bore solenoid for particles spectrometry, and the hadron-hadron FCC hh, CERN is developing an innovative design for the detector solenoids, to enable their positioning inside the calorimeters directly surrounding the inner tracker. For this to happen, the cryostat design has to be optimized to achieve minimum radiation length. The novel design consists of a sandwich of thin inner and outer metallic shells for vacuum tightness, supported by an insulating material with sufficient mechanical resistance paired with lowest thermal conductivity, like Cryogel, a flexible aerogel structure (density 0.16 g/cm3^3), or glass spheres (e.g. type K1 manufactured by 3M, with 65 μm diameter and density of 0.125 g/cm3^3). These materials would allow constructing a 4 m bore, 6 m long cryostat with a 250 mm total thickness, a heat load less than 400 W on the cold mass and 10 kW on the thermal shield. In this paper, design options are discussed and methods for qualifying the materials presented

    Clinical and Echocardiographic Outcomes of Transcatheter Tricuspid Valve Interventions: A Systematic Review and Meta-Analysis.

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    peer reviewedBACKGROUND: Medically managed tricuspid regurgitation (TR) has detrimental outcomes. Transcatheter tricuspid valve interventions (TTVIs) represent an alternative to surgery in high-risk patients; however, only early experiences exist. AIM: The aim of this study was to analyze the clinical and echocardiographic outcomes of TTVI. METHODS: MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to June 2021. Studies reporting data on outcome post-TTVIs were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was all-cause mortality at 30-day and 1-year post-TTVI. RESULTS: Out of 2,718 studies, 27 were included. Notably, 30-day and 1-year all-cause mortalities were 5% (95% confidence interval [CI]: 4-8%, p < 0.001) and 25% (95% CI: 12-45%, p = 0.016). Procedural success was associated with a 58% risk reduction in 1-year mortality vs. lack thereof (odds ratio 0.42, 95% CI: 0.27-0.66, p < 0.001). TTVI is associated with a significant reduction in TR severity (TR EROA, mean difference [MD] 0.31 cm(2); 95% CI: 0.23-0.39 cm(2), p < 0.001; regurgitant volume, MD 23.54 ml; 95% CI: 17.4-29.68 ml, p = 0.03) and increase in forward stroke volume (FSV, MD 3.98 ml; 95% CI: 0.11-7.86 ml, p = 0.04). CONCLUSION: TTVI significantly reduces TR severity and increases FSV and is associated with improved survival at 1 year compared with patients without procedural success. Long-term outcomes compared with medical therapy await the results of ongoing pivotal trials; nonetheless, TTVIs appear to be a promising alternative to surgery for TR

    Total occlusion of the abdominal aorta in a patient with renal failure and refractory hypertension: a case report

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    Total occlusion of the abdominal aorta is unusual, and potentially catastrophic. It occurs in patients with advanced atherosclerotic occlusive disease, and can cause severe ischemic manifestations, depending on the site of obstruction. Prompt and appropriate diagnostic and therapeutic approaches are important whenever this condition is suspected, in order to avoid a fatal outcome. The development of a complex network of collaterals may prevent the manifestation of acute ischemic phenomena, and cause a delay in diagnosis and treatment. Here we report the clinical case of a 59-year-old man who was referred to our Department for evaluation of renal failure and refractory hypertension. Ultrasonography and 99mTc-DTPA scintigraphy showed a shrunken, non-functioning left kidney, while CT angiography and aortography showed the complete occlusion of the aorta from below the right renal artery down to the bifurcation of both common iliac arteries, with a critical stenosis of the origin of the right renal artery, an occlusion of the left renal artery as well as of the origin of the inferior mesenteric artery. The patient was referred to the surgery department for aorto-bifemoral bypass surgery and re-implantation of the right renal artery

    New national and regional Annex I Habitat records: From #37 to #44

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    In this contribution, Italian new data concerning the distribution of the Annex I Habitats 3150, 3170*, 3260, 4090, 91L0, 91M0, 9340 are reported. In detail, 20 new occurrences in Natura 2000 sites are presented and 30 new cells are added in the EEA 10 km × 10 km reference grid. The new data refer to the Italian administrative regions of Campania, Lazio, Sardinia, Sicily, Tuscany, and Umbria

    An ex vivo model contributing to the diagnosis and evaluation of new drugs in cystic fibrosis

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    La fibrosi cistica (FC) è una malattia autosomica recessiva causata da mutazioni nel gene CFTR (Cystic Fibrosis Transmembrane conductance Regulator). Finora sono state descritte circa 2000 mutazioni, ma per la maggior parte di esse è difficile definirne leffetto senza complesse procedure in vitro. Abbiamo effettuato il campionamento (mediante brushing), la cultura e lanalisi di cellule epiteliali nasali umane (HNEC) utilizzando una serie di tecniche che possono aiutare a testare leffetto delle mutazioni CFTR. Abbiamo eseguito 50 brushing da pazienti FC e controlli, e in 45 casi si è ottenuta una coltura positiva. Utilizzando cellule in coltura: i) abbiamo dimostrato lespressione ampiamente eterogenea del CFTR nei pazienti e nei controlli; ii) abbiamo definito leffetto di splicing di una mutazione sul gene CFTR; iii) abbiamo valutato lattività di gating di CFTR in pazienti portatori di differenti mutazioni; iv) abbiamo dimostrato che il butirrato migliora in modo significativo lespressione di CFTR. I dati provenienti dal nostro studio sperimentale dimostrano che luso del modello ex-vivo di cellule epiteliali nasali è un importante e valido strumento di ricerca e di diagnosi nella studio della FC e può anche essere mirato alla sperimentazione ed alla verifica di nuovi farmaci. In definitiva, in base ai nostri dati è possibile esprimere le seguenti conclusioni: 1) il prelievo delle cellule epiteliali nasali mediante brushing è applicabile senza alcuna anestesia ed è ben tollerato da tutti i pazienti affetti da FC (bambini e adulti), è scarsamente invasivo e facilmente ripetibile, è anche in grado di ottenere una sufficiente quantità di HNECs rappresentative, ben conservate, idonee allo studio della funzionalità di CFTR; 2) la conservazione delle cellule prelevate è possibile fino a 48 ore prima che si provveda allallestimento della coltura e ciò permette di avviare studi multicentrici con prelievi in ogni sede e quindi di ottenere una ampia numerosità campionaria; 3) la coltura di cellule epiteliali nasali può essere considerata un modello adatto a studiare leffetto molecolare di nuove mutazioni del gene CFTR e/o mutazioni specifiche di pazienti carriers dal significato incerto; 4) il modello ex-vivo delle HNECs consente inoltre di valutare, prima dellimpiego nelluomo, leffetto di farmaci (potenziatori e/o correttori) sulle cellule di pazienti portatori di mutazioni specifiche di CFTR; tali farmaci possono modulare lespressione genica del canale CFTR aprendo così nuove frontiere terapeutiche e migliori prospettive di vita per pazienti affetti da una patologia cronica come la Fibrosi Cistica; 5) la metodologia da noi istituita risulta essere idonea alla misura quantitativa, mediante fluorescenza, dellattività di gating del canale CFTR presente nelle membrane delle cellule epiteliali nasali prelevate da pazienti portatori di differenti genotipi; in tal modo è possibile individuare: a) pazienti FC portatori di 2 mutazioni gravi con unattività < 10% (in rapporto ai controlli -100%), b) soggetti FC portatori contemporaneamente di una mutazione grave e di una lieve con unattività tra 10-30%, c) i cosiddetti portatori carriers- eterozigoti - con unattività tra 40-70%. In conclusione la possibilità di misurare lattività del canale CFTR in HNECs fornisce un importante contributo alla diagnosi di FC, mediante individuazione di un cut-off diagnostico, ed anche alla previsione della gravità fenotipica della malattia; quindi quanto rilevabile dalla misura del suddetto canale permette di prospettare per il futuro la possibilità di valutare meglio i pazienti per i quali il test del sudore ha dato risultati ambigui (borderline o negativi). La metodica da noi sperimentata consente anche di monitorare i pazienti durante il trattamento farmacologico, valutando in tal modo i reali effetti delle nuove terapie

    Outcomes of Patients with Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics

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    Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients
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