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Objectives Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy. We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). Methods In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. Results Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNF in prior anti-TNF agent failures. No differences were found according to type of adverse events or severe adverse events. Conclusions Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNF in TNF failures.

Axiom pinpointing refers to the task of highlighting (or pinpointing) the axioms in an ontology that are responsible for a given consequence to follow. This is a fundamental task for understanding and debugging very large ontologies. Although the name axiom pinpointing was only coined in 2003, the problem itself has a much older history, even if considering only description logic ontologies. In this work, we try to explain axiom pinpointing: what it is; how it works; how it is solved; and what it is useful for. To answer this questions, we take a historic look at the field, focusing mainly on description logics, and the specific contributions stemming from one researcher, who started it all in more than one sense.

Updating a knowledge base to remove an unwanted consequence is a challenging task. Some of the original sentences must be either deleted or weakened in such a way that the sentence to be removed is no longer entailed by the resulting set. On the other hand, it is desirable that the existing knowledge be preserved as much as possible, minimising the loss of information. Several approaches to this problem can be found in the literature. In particular, when the knowledge is represented by an ontology, two different families of frameworks have been developed in the literature in the past decades with numerous ideas in common but with little interaction between the communities: applications of AGM-like Belief Change and justification-based Ontology Repair. In this paper, we investigate the relationship between pseudo-contraction operations and gentle repairs. Both aim to avoid the complete deletion of sentences when replacing them with weaker versions is enough to prevent the entailment of the unwanted formula. We show the correspondence between concepts on both sides and investigate under which conditions they are equivalent. Furthermore, we propose a unified notation for the two approaches, which might contribute to the integration of the two areas.

Updating a knowledge base to remove an unwanted consequence is a challenging task. Some of the original sentences must be either deleted or weakened in such a way that the sentence to be removed is no longer entailed by the resulting set. On the other hand, it is desirable that the existing knowledge be preserved as much as possible, minimising the loss of information. Several approaches to this problem can be found in the literature. In particular, when the knowledge is represented by an ontology, two different families of frameworks have been developed in the literature in the past decades with numerous ideas in common but with little interaction between the communities: applications of AGM-like Belief Change and justification-based Ontology Repair. In this paper, we investigate the relationship between pseudo-contraction operations and gentle repairs. Both aim to avoid the complete deletion of sentences when replacing them with weaker versions is enough to prevent the entailment of the unwanted formula. We show the correspondence between concepts on both sides and investigate under which conditions they are equivalent. Furthermore, we propose a unified notation for the two approaches, which might contribute to the integration of the two areas.

Axiom pinpointing refers to the task of highlighting (or pinpointing) the axioms in an ontology that are responsible for a given consequence to follow. This is a fundamental task for understanding and debugging very large ontologies. Although the name axiom pinpointing was only coined in 2003, the problem itself has a much older history, even if considering only description logic ontologies. In this work, we try to explain axiom pinpointing: what it is; how it works; how it is solved; and what it is useful for. To answer this questions, we take a historic look at the field, focusing mainly on description logics, and the specific contributions stemming from one researcher, who started it all in more than one sense.

Background: Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. Methods: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. Results: Sixty-nine children, age 0-24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. Conclusion: The use of po

Background: Pediatric ARDS still represents a difficult challenge in Pediatric Intensive Care Units (PICU). Among different treatments proposed, exogenous surfactant showed conflicting results. Aim of this multicenter retrospective observational study was to evaluate whether poractant alfa use in pediatric ARDS might improve gas exchange in children less than 2 years old, according to a shared protocol. Methods: The study was carried out in fourteen Italian PICUs after dissemination of a standardized protocol for surfactant administration within the Italian PICU network. The protocol provides the administration of surfactant (50 mg/kg) divided in two doses: the first dose is used as a bronchoalveolar lavage while the second as supplementation. Blood gas exchange variations before and after surfactant use were recorded. Results: Sixty-nine children, age 0-24 months, affected by Acute Respiratory Distress Syndrome treated with exogenous porcine surfactant were enrolled. Data collection consisted of patient demographics, respiratory variables and arterial blood gas analysis. The most frequent reasons for PICU admission were acute respiratory failure, mainly bronchiolitis and pneumonia, and septic shock. Fifty-four children (78.3%) had severe ARDS (define by oxygen arterial pressure and inspired oxygen fraction ratio (P/F) < 100), 15 (21.7%) had moderate ARDS (100 < P/F < 200). PO2, P/F, Oxygenation Index (OI) and pH showed a significant improvement after surfactant use with respect to baseline (p < 0.001 at each included time-point for each parameter). No significant difference in blood gas variations were observed among four different subgroups of diseases (bronchiolitis, pneumonia, septic shock and others). Overall, 11 children died (15.9%) and among these, 10 (90.9%) had complex chronic conditions. Two children (18.2%) died while being treated with Extracorporeal Membrane Oxygenation (ECMO). Mortality for severe pARDS was 20.4%. Conclusion: The use of po

This paper describes a ∼200 m-thick section of the Pisco Formation exposed at Cerro Colorado, an important fossiliferous site in the Ica desert. In order to properly place the fauna in its correct relative position, this study establishes the stratigraphic framework within which the different fossil-bearing intervals of this site can be compared and may prove invaluable in future high-resolution studies on the faunal change. Most of the Pisco Formation deposits exposed at Cerro Colorado consist of gently dipping fine-grained sandstones, diatomaceous siltstones and diatomites with minor ash layers and dolomites deposited within nearshore and offshore settings. To facilitate detailed stratigraphic correlations within the Pisco strata for a 30 km2area, eight marker beds have been defined and large-scale (1:10,000 scale) geological mapping conducted to determine fault positions, styles and offsets. The geological map shows that there are two important angular unconformities in the study area. The first one is the interformational basal unconformity of the Pisco Formation against folded, faulted, and planated Oligo-Miocene rocks of the Chilcatay Formation. The second is a low-angle intraformational erosional discontinuity of up to 4° angular discordance that allows the subdivision of the Pisco stratigraphy exposed in the study area into two informal allomembers. Dating of the exposed succession by diatom biostratigraphy suggests that the age of the lower allomember is late Miocene, whereas the upper allomember is late Miocene or younger.

Objective: We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. Methods: A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. Results: According to Cohen’s criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. Conclusions: WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers’ experience. Key Points: • MDCT represents a reproducible technique for defining bone disease in MM. • Overall inter-observer agreement is good, even when comparing two different protocols. • Influence of readers’ experience on image analysis is partial.

One-hundred and ninety-two fossil marine vertebrate specimens, preserved as bone elements cropping out at Cerro Los Quesos (Pisco Basin, Peru), are identified and reported on a 1:4,000 scale geological map and in the corresponding stratigraphic section. All the fossils originate from the Pisco Formation, which is dated in this area to the late Miocene (from 7.55 Ma to ≥6.71 Ma, based on40Ar/39Ar analyses of three volcanic ash layers along the section). Specimens are particularly concentrated near the top of the two main hills, where the geologically youngest portion of the examined section crops out. The impressive fossil assemblage includes cetaceans (91.6%), represented by mysticetes (balaenopteroids and cetotheriids) and odontocetes (phocoenids, physeteroids, and ziphiids, including the holotype of Nazcacetus urbinai). Seals, a crocodile, a seabird, bony fish, and sharks are also reported. Isolated large teeth of Carcharocles and Cosmopolitodus are common and, in several instances, associated to mysticete skeletons. Together with a similar work recently published for the other late Miocene locality of Cerro Colorado, this work represents a case study for the detailed inventory of the extraordinary paleontological heritage of the Pisco Basin. As such, it constitutes the basis for future taphonomic, paleoecological, and systematic studies, as well as for a much-needed conservation effort.

This paper describes a ∼200 m-thick section of the Pisco Formation exposed at Cerro Colorado, an important fossiliferous site in the Ica desert. In order to properly place the fauna in its correct relative position, this study establishes the stratigraphic framework within which the different fossil-bearing intervals of this site can be compared and may prove invaluable in future high-resolution studies on the faunal change. Most of the Pisco Formation deposits exposed at Cerro Colorado consist of gently dipping fine-grained sandstones, diatomaceous siltstones and diatomites with minor ash layers and dolomites deposited within nearshore and offshore settings. To facilitate detailed stratigraphic correlations within the Pisco strata for a 30 km2area, eight marker beds have been defined and large-scale (1:10,000 scale) geological mapping conducted to determine fault positions, styles and offsets. The geological map shows that there are two important angular unconformities in the study area. The first one is the interformational basal unconformity of the Pisco Formation against folded, faulted, and planated Oligo-Miocene rocks of the Chilcatay Formation. The second is a low-angle intraformational erosional discontinuity of up to 4° angular discordance that allows the subdivision of the Pisco stratigraphy exposed in the study area into two informal allomembers. Dating of the exposed succession by diatom biostratigraphy suggests that the age of the lower allomember is late Miocene, whereas the upper allomember is late Miocene or younger.

One-hundred and ninety-two fossil marine vertebrate specimens, preserved as bone elements cropping out at Cerro Los Quesos (Pisco Basin, Peru), are identified and reported on a 1:4,000 scale geological map and in the corresponding stratigraphic section. All the fossils originate from the Pisco Formation, which is dated in this area to the late Miocene (from 7.55 Ma to ≥6.71 Ma, based on40Ar/39Ar analyses of three volcanic ash layers along the section). Specimens are particularly concentrated near the top of the two main hills, where the geologically youngest portion of the examined section crops out. The impressive fossil assemblage includes cetaceans (91.6%), represented by mysticetes (balaenopteroids and cetotheriids) and odontocetes (phocoenids, physeteroids, and ziphiids, including the holotype of Nazcacetus urbinai). Seals, a crocodile, a seabird, bony fish, and sharks are also reported. Isolated large teeth of Carcharocles and Cosmopolitodus are common and, in several instances, associated to mysticete skeletons. Together with a similar work recently published for the other late Miocene locality of Cerro Colorado, this work represents a case study for the detailed inventory of the extraordinary paleontological heritage of the Pisco Basin. As such, it constitutes the basis for future taphonomic, paleoecological, and systematic studies, as well as for a much-needed conservation effort.

The enormous concentration of marine vertebrates documented within the Pisco Formation is unique for Peru and South America and places this unit among the prime fossil Lagerstätten for Miocene to Pliocene marine mammals worldwide. In order to provide a robust stratigraphic framework for the fossil-bearing locality of Cerro Los Quesos, this study presents a 1:10,000 scale geological map covering an area of about 21 km2, a detailed measured section spanning 290 m of strata, and a refined chronostratigraphy for the studied succession well constrained by diatom biostratigraphy and high-resolution40Ar/39Ar isotopic dating of three interbedded ash layers. Within the apparently monotonous, diatomite-dominated sedimentary section, the Pisco Formation has been subdivided into six local members, with stratigraphic control over the different outcrops facilitated by the establishment of a detailed marker bed stratigraphy based on 15 readily distinguishable sediment layers of different nature.

Hundreds of fossil marine vertebrates cropping out at Cerro Colorado (Pisco Basin, Peru) are identified and reported on a 1:6500 scale geological map and in a joined stratigraphic section. All the fossils are from the lower strata of the Pisco Formation, dated in this area to the late middle or early late Miocene. They are particularly concentrated (88%) in the stratigraphic interval from 40 to 75 m above the unconformity with the underlying Chilcatay Formation. The impressive fossil assemblage includes more than 300 specimens preserved as bone elements belonging mostly to cetaceans (81%), represented by mysticetes (cetotheriids and balaenopteroids) and odontocetes (kentriodontid-like delphinidans, pontoporiids, ziphiids, and physeteroids, including the giant raptorial sperm whale Livyatan melvillei). Seals, crocodiles, sea turtles, seabirds, bony fish, and sharks are also reported. Isolated large teeth of Carcharocles and Cosmopolitodus are common throughout the investigated stratigraphical interval, whereas other shark teeth, mostly of carcharinids, are concentrated in one sandy interval. This work represents a first detailed census of the extraordinary paleontological heritage of the Pisco Basin and the basis for future taphonomic, paleoecological, and systematic studies, as well as a much needed conservation effort for this extremely rich paleontological site.

Background: The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed. Methods: Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade ≥III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity. Results: Incidence of grade ≥III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade ≥III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome. Conclusion: Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine aminotransferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors. © 2005 Torti et al; license BioMed Central Ltd.

Background: The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed. Methods: Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade ≥III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity. Results: Incidence of grade ≥III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade ≥III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome. Conclusion: Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine aminotransferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors. © 2005 Torti et al; license BioMed Central Ltd.

The Mio-Pliocene Pisco Formation (Peru) is a world-famous marine vertebrate Lagerstätte. Several fossil specimens are wrapped up in dolomitic nodules. Some others lie in the sediment displaying dolomite only in bone cavities (e.g., mesorostral canal and endocranium). With the aim to understand whether the precipitation of the dolomitic nodules influenced the formation of the Lagerstätte, we collected field data on a high number of fossil vertebrates and conducted petrographic and mineralogical analyses on samples representative of the variable development of concretions. Our results revealed positive relationships between size, completeness and articulation of skeletons and the presence of an external nodule. Clear evidence of chemoautotrophic communities that thrived on the carcasses is scarce. Microborings are often found in the cortical bone tissues together with iron oxides; the former are left by microorganisms feeding on the carcass, the latter are traces of former Fe sulphides, a product of organic matter degradation. We suggest that an early burial of the skeletons was a determinant factor in the development of dolomite concretions, since it allowed methanogenesis and anaerobic sulphate reduction exploiting the lipids in the bones and the organic matter dispersed in the sediments. Dolomite precipitation was driven by the same bacteria operating during the suphophilic stage of whale-fall communities. Textural observations imply that dolomite precipitated shortly after the burial of carcasses. The increase of alkalinity generated by sulphate reduction and methanogenesis caused a rapid precipitation of the dolomite within skeletal cavities and prevented the degradation of the bones and diagenetic compression of skeletons; the nodules themselves prevented erosion of fossils after exhumation. Therefore, nodule formation had a crucial role in the development of the Pisco Lagerstätte.

Laminated diatomaceous mudstones are the most characteristic lithology of the Mio- Pliocene Pisco Formation, Ica desert, Peru; discrete tuff layers intercalate to them. The Pisco Fm. deposited during the Neogene in the East Pisco Basin, one of the Andean forearc basins which run eastward of the Peru-Chile trench. Nowadays, the Pisco Fm. is one of the most famous Fossillagerstätte in the world. Its popularity is due to the great abundance of exceptionally well preserved marine vertebrates, especially cetaceans, lying in the diatomaceous mudstone. Many specimens are indeed fully articulated and often concentrated in horizontal accumulation layers. This study is meant to understand how diatom deposition may have positively interfered in the genesis of this Fossillagerstätte, by: 1) analyzing diatom laminae and their different assemblages and obtaining information on the seasonality affecting the water column during deposition of the Pisco Fm.; 2) recognizing and evaluating any evidence of exceptional harmful algal blooms (HABs) coinciding with the fossil vertebrate accumulation levels; HABs were recently evoked to explain four discrete horizons showing fossil marine vertebrates accumulation in the late Miocene of Atacama desert, Chile (Pyenson et al., 2014); 3) investigating the hypothesis that diatom and diatom mats deposition may have favored the preservation of vertebrates by lowering the level of dissolved oxygen on the sea floor; indeed, these conditions would have prevented the development of a whale-fall community that generally leads to the fast decay of the carcasses and the final disarticulation of skeletons; 4) evaluating the sedimentation rates of the diatomaceous mudstones to understand how long it would have taken for a carcass to be completely buried, thus, verifying whether fossil preservation is mainly due to the high sedimentation rates of diatomaceous mudstones as suggested by Brand et al. (2004); Moreover, we are investigating diatom assemblages c

The Mio-Pliocene Pisco Formation (Ica Desert, Peru) is known for its vast outcrops, which preserve one of the richest concentrations of fossil marine vertebrates on Earth. During the last thirty years, punctual studies carried out on several exceptionally well preserved individual specimens highlighted the extraordinary diversity of vertebrates that populated the area: cetaceans, pinnipeds, turtles, sea birds, and fishes are just a few examples. Through our successive fieldwork campaigns, for the first time a detailed taphonomic and stratigraphic study of the fossil assemblages from localities of the oldest strata (middlelate Miocene) of the Pisco Fm. was undertaken. Stratigraphy was used to correctly assign specimens to well-defined strata and, consequently, to evaluate the temporal variation in the composition and concentration of the fossils along the investigated stratigraphical sequence. GPS data were collected for all the fossil vertebrates and a preliminary systematic determination was carried out in the field for all the specimens, while the most interesting and well-preserved ones were taken in laboratory for preparation and detailed study. Taphonomic observations were also carried out: orientation of the skeletons, skeletal completeness, bone articulation, associated invertebrates, associated shark teeth, and evidence of bioerosion. Sediment samples enclosing the fossils were collected along the continuous vertical diatomaceous mudstone sequences and were examined through different analyses (grain size analyses, micropalaeontological analyses, major and minor elements analyses, etc.) to understand the condition of burial and to obtain a more precise dating of the fossiliferous layers, using calcareous nannoplankton (where present), diatoms, silicoflagellates, radiolarians, and dinoflagellates as biostratigraphic markers. Some of these microfossils were also used to measure as proxies to infer on paleo-depth and water paleo-temperature. Samples for radiomet

The combination of Fuzzy Logics and Description Logics (DLs) has been investigated for at least two decades because such fuzzy DLs can be used to formalize imprecise concepts. In particular, tableau algorithms for crisp Description Logics have been extended to reason also with their fuzzy counterparts. Recently, it has been shown that, in the presence of general concept inclusion axioms (GCIs), some of these fuzzy DLs actually do not have the finite model property, thus throwing doubt on the correctness of tableau algorithm for which it was claimed that they can handle fuzzy DLs with GCIs. In a previous paper, we have shown that these doubts are indeed justified, by proving that a certain fuzzy DL with product t-norm and involutive negation is undecidable. In the present paper, we show that undecidability also holds if we consider a t-norm-based fuzzy DL where disjunction and involutive negation are replaced by the constructor implication, which is interpreted as the residuum. The only condition on the t-norm is that it is a continuous t-norm "starting" with the product t-norm, which covers an uncountable family of t-norms. © 2011 Springer-Verlag.

The combination of Fuzzy Logics and Description Logics (DLs) has been investigated for at least two decades because such fuzzy DLs can be used to formalize imprecise concepts. In particular, tableau algorithms for crisp Description Logics have been extended to reason also with their fuzzy counterparts. Recently, it has been shown that, in the presence of general concept inclusion axioms (GCIs), some of these fuzzy DLs actually do not have the finite model property, thus throwing doubt on the correctness of tableau algorithm for which it was claimed that they can handle fuzzy DLs with GCIs. In a previous paper, we have shown that these doubts are indeed justified, by proving that a certain fuzzy DL with product t-norm and involutive negation is undecidable. In the present paper, we show that undecidability also holds if we consider a t-norm-based fuzzy DL where disjunction and involutive negation are replaced by the constructor implication, which is interpreted as the residuum. The only condition on the t-norm is that it is a continuous t-norm "starting" with the product t-norm, which covers an uncountable family of t-norms. © 2011 Springer-Verlag.

Background: The independent role of HCV genotype 3 (HCV-3) in dyslipidaemia following highly active antiretroviral therapy (HAART) is still unexplored. Methods: Analysis of data from a cohort of 307 HIV/HCV-coinfected patients and 415 HIV-monoinfected controls was conducted. Patients with available lipid levels at baseline and minimum 3-month follow-up were ranked into three groups by HCV status (HCV-3, other HCV genotypes or HCV negative). Univariate and multivariate GEE models were performed to assess factors correlated with lipid serum levels as coefficient (Coef., defined as mean difference [mg/dl] across the follow-up). Univariate and multivariate logistic regression analyses were performed for prediction of relevant hypertriglyceridaemia (> or = 500 mg/dl) and relevant hypercholesterolaemia (> or = 240mg/dl) at 3 months of follow-up. Results: HCV-3 correlated with lower triglyceridaemia (Coef.=-38.22; P=0.001), independently from the other considered variables, including age, gender and use of stavudine or lopinavir. Even though HCV infection per se appeared to be protective, HCV-3 in particular was also independently associated with lower cholesterolaemia (Coef.=-46.35; P<0.001). At logistic regression analyses, HCV-3, but not HCV-non-3, was associated with lower risk of relevant hypercholesterolaemia (odds ratio [OR] 0.06; P=0.01) and relevant hypertriglyceridaemia (OR 0.11; P=0.05), independently from other considered variables. Conclusions: Our data confirm that HCV coinfection per se is associated with lower risk of hypercholesterolaemia after HAART. This effect was particularly attributed to HCV-3, which was the only genotype associated with lower triglyceridaemia during HAART.

Background & Aims: This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease. Methods: Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients. Protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (LT). Results: A fully mismatched donor/recipient pair at the DRB1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the LC (59% vs 23%, P = .0002) and its progression beyond stage 3 in the CSPD (71.4% vs 39.3%, P = .0003). Relevant immunologic and nonimmunologic variables were included into a multivariate Cox proportional model and three variables, namely, donor age, full HLA-DRB1 donor-recipient mismatch, and HLA B14, resulted in independent risk factors for the development of severe fibrosis. Conclusion: This study provides evidence that DRB1 donor-recipient mismatch affects both the occurrence and progression of recurrent hepatitis C disease. This information is clinically relevant as it may help to better allocate organs and to recognize patients at risk for progression so that specific interventions can be implemented. © 2006 by the American Gastroenterological Association Institute

Objective: In 55 prepubertal children with growth failure, aged 8.62 +/- 2.89 years, we evaluated the efficacy of a test using only half the usual dose of insulin by comparing the results with those obtained during a classical arginine tolerance test, performed separately. Patients and Methods: The patients were randomly divided into two groups: group A consisting of 37 children received 0.05 U/kg insulin, while group B consisting of 18 patients received 0.1 U/kg insulin. Each child received the same dose of arginine per kg during the second test. Results: Serum growth hormone (GH) peak levels were significantly (p <0.01) lower in children of group A (6.59 +/- 4.10 ng/ml) than in those of group B (10.12 +/- 5.80 ng/ml). No differences of GH peak levels were found in patients of the two groups after arginine infusion. The injection of 0.05 U/kg insulin induced a significantly (p <0.0001) lower percent decrease of serum glucose than 0.1 U/kg. No difference of the percent increase of serum cortisol induced by insulin at 0.05 U/kg and 0.1 U/kg was observed. Conclusion: The diagnosis of GH deficiency in children can be supported by a blunted GH response after two or more pharmacological stimuli including hypoglycaemia induced by only half the usual dose of insulin.

Study objectives: To evaluate earl and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s.Designs: Prospective cohort.Setting: A university department of pediatrics.Participants: Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study.Measurements: Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. Results: Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for kite abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p < 0.05).Conclusions: These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be clue to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.

Background-Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting.Methods-A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies.Results-No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p<0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07).Conclusions-In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and should have active