Fuzzy Esscher changes of measure and copula invariance in Lévy markets

In the context of a multidimensional exponential Lévy market, we focus on the Esscher change of measure and suggest a more flexible tool allowing for a fuzzy version of the standard Esscher transform. Motivated both by the empirical incompatibility of market data and the analytical form of the standard Esscher transform (see [8]) and by the desire to introduce a pricing technique under incompleteness conditions, we detect the impact of fuzziness in terms of measure change function and in contingent claims' pricing. In a multidimensional setting the fuzzy Esscher transform is a copula whose invariance, under margins' transformations induced by a change of measure, is investigated and connected to the notion of the absence of arbitrage opportunities. We highlight how Esscher transform, primarily used in pricing techniques, preserves the invariance of the aggregation operator and it can be generalized to the fuzzy version assuming that the measurable functions defining the Choquet marginal integrals are increasing. Furthermore, the empirical evidence seems to suggest that a weaker concept of invariance may be more suitable, i.e. the ε-measure invariance, coherent with the Esscher fuzzy copula tool. An empirical experiment for our model will make clear how this blurring technique fits the market data

Opis svojstava ekstra djevičanskog maslinovog ulja dobivenog iz raznih kultivara

The determination of some minor components of extra virgin olive oil, and in particular of the polyphenolic fraction of pigments and fragrances, can contribute to the characterization of the monovarietal productions: the quali-quantitative assessment of these substances can in fact contribute to the valorisation of typicalities and, at the same time, consent to the optimisation of the operational techniques during the processing and the eventual blending. The analytical techniques, applied here for the characterisation of extra virgin olive oil of Abruzzo and Istria, have highlighted that chemical composition can enhance the valorisation of these typical products. Nevertheless, further sampling program is needed to evidence typical composition profile that might be used as “origin markers”.Određivarije nekih manjih komponenata ekstra djevičanskog maslinovog ulja, naročito polifenolne frakcije pigmemta i mirisa, može doprinijeti svojstvima monovarijetetnih proizvoda: kvalitativna i kvalitativna procjena tih supstancija može zapravo doprinijeti valorizaciji tipičnosti te, istodobno omogućiti optimizaciju operativnih tehnika za vrijeme prerade i miješanja. Analitičke tehnike, ovdje primijenjene za opis svojstava ekstra djevičanskog maslinovog ulja iz Abruzza i Istre pokazuju da kemijski sastav može popraviti vrijednost ovih tipičnih proizvoda. Ipak, potreban je dodatni program uzorkovanja da se dokaže tipični profil sas¬tava, što se može upotrijebiti kao "oznaka podrijetla"

Clinical and molecular characterization of 40 patients with classic Ehlers--Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS

Connective tissue anomalies in patients with spontaneous cervical artery dissection.

OBJECTIVE: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD). METHODS: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD. RESULTS: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045). CONCLUSIONS: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease

Antithrombotic medications and the etiology of intracerebral hemorrhage: MUCH-Italy.

23noOBJECTIVE: To test the hypothesis that the effect of antithrombotic medications on the risk of intracerebral hemorrhage (ICH) varies according to the location of the hematoma. METHODS: Consecutive patients with ICH were enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Multivariable logistic regression models served to examine whether risk factors for ICH and location of the hematoma (deep vs lobar) predict treatment-specific ICH subgroups (antiplatelets-related ICH and oral anticoagulants [OACs]-related ICH). RESULTS: A total of 870 (313 lobar ICH, 557 deep ICH) subjects were included. Of these, 223 (25.6%) were taking antiplatelets and 77 (8.8%) OACs at the time of stroke. The odds of antiplatelet-related ICH increased with aging (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.03-1.07) and hypertension (OR 1.86; 95% CI 1.22-2.85) but had no relation with the anatomical location of ICH. Conversely, lobar location of the hematoma was associated with the subgroup of OAC-related ICH (OR 1.70; 95% CI 1.03-2.81) when compared to the subgroup of patients taking no antithrombotic medications. Within the subgroup of patients taking OACs, international normalized ratio (INR) values were higher in those with lobar ICH as compared to those with deep ICH (2.8 ± 1.1 vs 2.2 ± 0.8; p = 0.011). The proportion of patients with lobar hematoma increased with increasing intensity of anticoagulation, with a ∼2-fold increased odds of lobar compared to deep ICH (odds 2.17; p = 0.03) in those exposed to overanticoagulation (INR values >3.0). CONCLUSIONS: OACs, as opposed to antiplatelets, predispose to lobar location of brain hematomas according to a dose-response relationship.openopenPezzini, A; Grassi, M; Paciaroni, M; Zini, A; Silvestrelli, G; Del Zotto, E; Caso, V; Dell'Acqua, Ml; Giossi, A; Volonghi, I; Simone, Am; Lanari, A; Costa, P; Poli, L; Morotti, A; De Giuli, V; Pepe, D; Gamba, M; Ciccone, A; Ritelli, M; Colombi, M; Agnelli, G; Padovani, APezzini, Alessandro; Grassi, M; Paciaroni, M; Zini, A; Silvestrelli, G; Del Zotto, E; Caso, V; Dell'Acqua, Ml; Giossi, A; Volonghi, I; Simone, Am; Lanari, A; Costa, P; Poli, L; Morotti, A; De Giuli, V; Pepe, D; Gamba, M; Ciccone, A; Ritelli, M; Colombi, Marina; Agnelli, G; Padovani, Alessandr

GLUT10-Lacking in Arterial Tortuosity Syndrome-Is Localized to the Endoplasmic Reticulum of Human Fibroblasts.

GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the SLC2A10 gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS). Since subcellular distribution of the transporter is dubious, we aimed to clarify the localization of GLUT10. In silico GLUT10 localization prediction suggested its presence in the endoplasmic reticulum (ER). Immunoblotting showed the presence of GLUT10 protein in the microsomal, but not in mitochondrial fractions of human fibroblasts and liver tissue. An even cytosolic distribution with an intense perinuclear decoration of GLUT10 was demonstrated by immunofluorescence in human fibroblasts, whilst mitochondrial markers revealed a fully different decoration pattern. GLUT10 decoration was fully absent in fibroblasts from three ATS patients. Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI). The results demonstrate that GLUT10 is present in the ER

Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport

Loss-of-function mutations in the gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS), a rare connective tissue disorder. In this study GLUT10-mediated dehydroascorbic acid (DAA) transport was investigated, supposing its involvement in the pathomechanism. GLUT10 protein produced by in vitro translation and incorporated into liposomes efficiently transported DAA. Silencing of GLUT10 decreased DAA transport in immortalized human fibroblasts whose plasma membrane was selectively permeabilized. Similarly, the transport of DAA through endomembranes was markedly reduced in fibroblasts from ATS patients. Re-expression of GLUT10 in patients’ fibroblasts restored DAA transport activity. The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients

GARFIELD-NGS: Genomic vARiants FIltering by dEep Learning moDels in NGS

Exome sequencing approach is extensively used in research and diagnostic laboratories to discover pathological variants and study genetic architecture of human diseases. However, a significant proportion of identified genetic variants are actually false positive calls, and this pose serious challenge for variants interpretation. Here, we propose a new tool named Genomic vARiants FIltering by dEep Learning moDels in NGS (GARFIELD-NGS), which rely on deep learning models to dissect false and true variants in exome sequencing experiments performed with Illumina or ION platforms. GARFIELD-NGS showed strong performances for both SNP and INDEL variants (AUC 0.71-0.98) and outperformed established hard filters. The method is robust also at low coverage down to 30X and can be applied on data generated with the recent Illumina twocolour chemistry. GARFIELD-NGS processes standard VCF file and produces a regular VCF output. Thus, it can be easily integrated in existing analysis pipeline, allowing application of different thresholds based on desired level of sensitivity and specificity. Availability and implementation: GARFIELD-NGS available at https://github.com/gedoardo83/GARFIELD-NGS