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Significant progress in the diagnosis and classification of pleural mesothelioma has been made in the past 5 years. Novel biomarkers are now entering more widespread use following major advances in understanding the genomic landscape of the malignancy. As the diagnosis and management of mesothelioma becomes more multidisciplinary together with the increasing role of histopathology in providing additional prognostic information to guide downstream management, we review herein newly proposed prognostic variables, diagnostic biomarkers, utility of pleural effusion cytology in diagnosis, and mesothelioma surgery. A section on the upcoming WHO classification on malignant pleural mesothelioma is also included.

AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (1) externally validate the prognostic role of pleomorphic features in E-MPM and (2) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared those without (5.4 months vs 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 months vs. 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

SummaryLung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (P=3.4×10−4), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (P−6). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (P−16). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.

Connective tissue diseases (CTDs) are a heterogeneous group of disorders, acquired or hereditary, involving an autoimmune-mediated inflammation of connective tissues in the whole body. Lung involvement is common with CTDs, and associated with significant morbidity and mortality. Each compartment of the lung may be affected, often simultaneously, depending on the type of CTD. In addition, the lung may show pathological changes related to treatment, such as infection, drug reaction, and neoplasia. A multidisciplinary approach to diagnose these patients is essential and incorporates radiological and clinical as well as pathological data. In this review we describe the patterns of lung disease associated with common CTDs, lung disease in pediatric CTD patients, and newly recognized conditions.

Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P

Summary The objective of reservoir characterization is to understand the reservoir rocks and fluids through accurate measurements: in this context seismic inversion plays a dominant role in providing the structural framework and an estimation of rock properties. The advent of the Controlled-Source EM methodology, producing an estimate of the subsurface resistivity, brought the multiphysics data into the characterization workflow traditionally dominated by seismic and significantly enhanced the accuracy of the estimated rock and fluid properties. This work constitutes a first step towards the generalization of a framework that can exploit all the available geophysical measurements and properties for an improved understanding of reservoir uncertainties. We introduce two approaches to for the multigeophysical reservoir characterization: the first one is deterministic while the second is statistical. The two workflows have in common the rock-physics model that computes the geophysical properties from the petrophysical ones while they differ in the way the inversion step for the estimation of the reservoir properties from the observations is implemented. We evaluate the workflows on an offshore oil field where 3D seismic, 3D CSEM data and well logs are available.

The use of biodegradable polymers has aroused academic and technological interest directed to the replacement of conventional polymers aiming at reducing the environmental impact caused by these materials. Vegetable fibres as reinforcement elements provide gains in mechanical, thermal and degradation properties to polymer composites. The buriti fibre (Mauritia flexuosa) is an abundant crop of easy cultivation in tropical countries and its use in composites with poly(lactic acid) (PLA), can provide the development of a material with specific features, combining good mechanical properties and excellent degradation potential to the obtained composites. In this research, PLA and buriti fibre composites were developed with the use of triacetin as coupling agent. For a 30% content by mass of fibre, the results showed that the mechanical properties of the composites were similar to those of neat PLA. This was attributed to the fibre/matrix interaction observed by the SEM analysis and to an increase in crystallinity assessed by thermal properties.

Introduction There is limited evidence regarding the optimal number of sampling sites and specimen dimension in histological diagnosis of malignant pleural mesothelioma (MPM). Previously we have validated 2-tier nuclear grade as an independent predictor of survival in epithelioid MPM. This study evaluates the association between sampling parameters and the performance of 2-tier nuclear grade and growth pattern as survival predictors using a biopsy-heavy cohort. Methods Clinicopathological information including the number of sampling sites, tissue dimension, 2-tier nuclear grade, predominant growth pattern and overall survival (OS) were retrieved from an institutional mesothelioma database comprising 614 consecutive cases of epithelioid MPM over a 15 year period. Survival analysis was performed using Kaplan-Meier method. Association between categorical variables was analysed using Fisher exact test, and was assessed in relation to biopsy size and number. Statistical significance was defined as p Results The mean age was 69.1 years, with male preponderance (75.6%). 87.0% (534/614) received biopsy only. The median number of sites sampled was 1 (range 1–20). The median maximum tissue dimension was 18 mm for biopsies (range 2–140 mm) and 145 mm for resections (range 40–350 mm). 17.7% of all biopsies (95/534) were taken from a single site with a maximum dimension of ≤10 mm (median: 8 mm). Low grade tumours showed significantly prolonged OS compared with high grade (19.3 months vs. 8.9 months, p Conclusions We propose an optimal sampling standard of 3 sites or a maximum tissue dimension of ≥20 mm from a single site. This then allows a 2-tier nuclear grading system to provide prognostic stratification for clinical care and research of epithelioid MPM.

Borders are often regarded as the very basis for establishing a modern and territorial logic legitimating an essentialised view of the world as a mosaic of Nation-States. Transnationalism seems to challenge this long-standing logic by introducing a new inclination to think in terms of flows, mobility, and networks. By living in-between sending and receiving societies and maintaining strong ties to both, Migrants are shaping transnational spaces encompassing several countries in a process that challenges territorial separations and national borders. However, migration challenges borders, but is still regulated by borders. It may overcome some borders, but it does not in itself prevent the creation of other borders that recreate divisions along other lines. Accordingly, borders have not been disappearing but they are moving themselves everywhere. This dis-placement of borders can be conceived as a paradoxical movement from the ‘edge’ to the ‘centre’ of public space. Following this, what is worth exploring is how such b-ordering processes are in the very heart of European identity and citizenship that are defined in the complex interplay between moving, dis-located external borders and the multiplication of internal ones. Both external and internal borders point to a set of relevant issues: the former are related to (im)migration policies, diasporas as well as transnationalism; the latter focus instead on different forms of ethnicisation, old and new racisms, citizenship, as well as the idea of nation and the processes of social differentiation it implies. The attention to the complex relationship between internal and external borders, still largely ignored by social studies, is a relevant starting point for reconceptualising borders and their connections with transnational migration. Indeed, it has empirical reasons, due to the involvement of the same actors and of the same forms of power that are implied in both cases, and theoretical reasons, because the changes affecting both these kinds of borders reveal deep changes in the national space borders, in the forms of social identification, in the politics and in the practices concerning migrants.

The paper deals with the study of the spatial distribution and the design of sampling plans for estimating nymph densities of the grape leafhopper Scaphoideus Titanus in vine plant canopies.

BACKGROUND Tuberculosis prevention has been based on generalized BCG vaccination in France since 1949. The aim of this cross-sectional survey was to assess the impact of the change in BCG administration (in January 2006) and the end of compulsory vaccination (in July 2007). METHOD A self-administered postal questionnaire was sent to a random sample of 2248 physicians practicing in 6 departments in the Rhone-Alpes region in 2008. RESULTS Overall, 923 questionnaires were analyzed. The median age of the respondents was 52 years, 67 % were male, 93 % were general practitioners, and 91 % practiced in private practice offices. The median number of BCG vaccines administered on a quarterly basis was 5 (interquartile range [IQR], 3-10) before January 2006, one (IQR, 0-3) between January 2006 and July 2007, and zero (IQR, 0-1) after July 2007 (P

The objective of this study was to assess the efficacy and safety of moxifloxacin versus amoxicillin-clavulanate plus roxithromycin (comparator) in adult community-acquired pneumonia (CAP) patients with risk factors. In this comparative, randomized, multicenter, open-label study, patients hospitalized for CAP received a 10-day oral treatment with either moxifloxacin (400 mg o.d.) or amoxicillin-clavulanate (1,000/125 mg t.i.d.) plus roxithromycin (150 mg b.i.d.). Clinical and bacteriological outcomes were assessed during test of cure and follow-up visits (5-7 days and 21-28 days after the end of treatment, respectively). Of 349 randomized patients, 346 were included in the intent-to-treat analysis and 289 in the per-protocol analysis. Their baseline characteristics were comparable. The most frequent risk factors for mortality were age >65 years (50.0%), alcoholism (23.1%), and comorbidities (50.6%); chronic obstructive pulmonary disease (COPD) (25.4%) and diabetes mellitus (13.6%) were the most common associated comorbidities. A causative pathogen was documented in 66 of 346 (19.1%) of the patients (including 21 with positive blood cultures). Respective per-protocol clinical success rates at test-of-cure (primary efficacy endpoint) for moxifloxacin and comparator were 131 of 151 (86.8%) and 120 of 138 (87.0%), with a 95% confidence interval (CI) of -8.0-7.6 for the difference. Bacteriological success rates (eradication) were 23 of 30 (76.7%) and 23 of 31 (74.2%); rates for patients with positive blood cultures were 10 of 14 and 4 of 6. Persistent clinical success rates at follow-up were 118 of 120 (98.3%) and 102 of 106 (96.2%), with a 95%CI of -2.2-6.4 for the difference. The intent-to-treat analysis confirmed these results. Adverse events associated with moxifloxacin and the comparator drug were reported for 42 of 171 (24.6%) and 50 of 175 (28.6%) of the patients, respectively, and comprised predominantly digestive disorders, which occurred in 9.4% and 21.1%. On the basis of these results, once-daily oral moxifloxacin alone is as effective as amoxicillin-clavulanate plus roxithromycin for the treatment of CAP in patients with risk factors.

The work discusses the validity of using Fremingham risk estimates in populations in which no baseline risk is well established and propose a tool which could provide more accurate risk estimates.

The aim of this study was to assess the effects of PM10 daily concentrations in urban ambient air on bronchial reactivity and on two indices of respiratory function (FEV1 and PEF) of healthy control (n = 20) and of mild asthmatic adults (n = 20). The study took place over two periods of a month and a half, during summer 1996 and winter 1997. Each volunteer underwent two methacholine challenge tests, one during a weekday, the other early on the next Monday morning, after a weekend of lower exposure. They also monitored their FEV1 and PEF twice daily with an electronic peak flow meter. The respiratory function decreased among asthmatic subjects a few days after daily PM10 levels had increased (−1.25% for FEV1, 95% CI = [−0.58, −1.92]; and −0.87% for PEF [−0.1, −1.63], for a daily 10 μg m−3 variation of PM10 in summer; −0.25% [−0.51, 0.02] for FEV1 only in winter). No association between daily variations of respiratory function and PM10 was observed among control subjects. Bronchial reactivity was not significantly different between the two days of methacholine tests among asthmatic and control subjects, either in summer or in winter. This study confirms the greater sensitivity of asthmatic adults, compared with healthy subjects, to short-term variations of ambient air concentrations of particles. However, bronchial reactivity is not modified by small short-term variations of particulate pollution among mild asthmatics or healthy subjects. Copyright © 1999 John Wiley & Sons, Ltd.

Resume Un essai multicentrique, comparatif, randomise, en ouvert pour chaque groupe traite a ete mene en ville, avec un plan statistique visant a mettre en evidence l'equivalence de deux types de strategies de traitement (josamycine 5 jours — azithromycine 5 jours). Compte tenu de la demonstration faite de l'equivalence entre les therapeutiques etudiees, une analyse complementaire a ete realisee. Pour cette analyse economique, la strategie envisagee est, a duree de traitement egale (5 jours), celle de la minimisation de cout : on cherche a mettre en evidence la strategie pour laquelle les couts induits sont les moins importants. Le cout moyen direct pour l'Assurance Maladie (consommations de soins) s'eleve a 221 F dans le groupe josamycine 5 jours et a 258 F dans le groupe azithromycine 5 jours (p

Resume L'objectif de cette etude multicentrique, prospective, randomisee, en double aveugle, etait de comparer l'efficacite et la tolerance du cefotiam hexetil (CTM) a la dose de 400 mg matin et soir avec celles de l'amoxicilline/acide clavulanique (AAC) a la dose de 1 g matin et soir sur une periode de dix jours de traitement au cours d'une exacerbation de bronchite chronique. Cent cinquante sept patients adultes souffrant d'une exacerbation de bronchite chronique ont ete inclus par des pneumologues. Les deux populations etaient comparables a l'inclusion en ce qui concerne les donnees demographiques et la clinique. En fin de traitement, 92 % des patients du groupe cefotiam hexetil et 88 % du groupe amoxicilline/acide clavulanique etaient gueris apres analyse en intention de traiter, respectivement 96 % versus 94 % apres analyse en per protocol. Le nombre d'effets secondaires a ete moins frequent dans le groupe cefotiam hexetil (9 % versus 21 %). Cette difference etait statistiquement significative (p = 0,03). En conclusion, le cefotiam hexetil 400 mg matin et soir peut etre considere comme une bonne alternative therapeutique dans le traitement des exacerbations de bronchite chronique de l'adulte avec une efficacite equivalente et une tolerance meilleure que l'amoxicilline/acide clavulanique 1 g matin et soir.

This work examined the influence of different chemical blowing agents (CBA), one endothermic and one exothermic, at the same concentration (2% by mass), on poly(acid lactic), PLA foams. The CBA was incorporated into the PLA in a single-screw extruder, and the foams were expanded by heating in an electric oven under free pressure conditions. Foam degradation in a simulated soil was performed according to the ASTM G160-03 standard. Changes in the physical-chemical, morphological and mechanical properties were used to evaluate the degradation. The results indicated that the different chemical blowing agents led to different mechanical and morphological properties for the foams, which resulted from the nature and decomposition rate of the blowing agents. Cells in the foams accelerated the degradation since they facilitated the infiltration of water toward the interior of the polymer and triggered the degradation process by hydrolysis.

The work examines factors which might influence insight and self-assessment quality of life in schizophrenia patients using CATIE dataset.

In this report, we describe the current state of progress of WP3 (shredding process modelling and simulation) at the end of the first project year and its associated deliverable: \An optimized stochastic model which, for every configuration of the process parameters, predicts the distribution of particle size and liberation degree classes". The following main results are achieved within WP3 and are reported in this deliverable: the development of a model for predicting the evolution of particle size distribution in a batch shredding process; the development of a method for designing the shredding experiments aiming at estimating the key parameters of the model; the development of a model estimation approach; a preliminary experimentation to investigate the dependency of the output size distribution on the process parameters and to choose a suitable chamber saturation for the next experimental validations. The experiments will be completed in the next two months and the model will be validated, with appropriate experiments, and optimized, as stated in the deliverable description. Further experiments will be designed to optimize a model for the discharge process. The analysis of the particle liberation degree will be carried out as part of the second project year activity, based on hyperspectral imaging or XRF particle analysis technologies. The modelling of the particle liberation degree as a function of the process parameters will be investigated, according to the description of work reported in the project proposal. This deliverable is organized as follows. In Section 2.2 we explain brie y the importance of modeling size reduction processes in mechanical recycling systems. In Section 2.3 we describe the Markov model for the evolution of the particle size distribution in a batch process. Simplifying assumptions are introduced with the purpose of minimizing the set-up time for model estimation (or \optimization") in different applied contexts, in view of the wide range of PCBs that could be processed in real life. Section 2.4 establishes requirements for model estimation, which contribute to determine the criteria for the design of experiments. Section 2.5 illustrates a preliminary experiment to choose a suitable comminution chamber saturation, to be used throughout the main experimental plan. In Section 2.6 we use information obtained from Section 2.5 to determine the number of replicated runs in the main experimental plan.

The work presents a method that uses Bayesian tools to monitor clinical trials, allowing early stopping for futility or, on the other side, emerging of early results for effectiveness.

This paper summarizes the methodology used for describing the spatial distribution of the grape leafhopper Scaphoideus titanus in a vineyard located in Southern Switzerland and presents sampling plans for research and management purposes. The sampling technique consisted of repeated visual counts of S. titanus nymphs. In general, a vineyard is a highly structured environment whose influence on spatial distributions is studied by analyses of variance and quantified by regression models developed in a stratified and multi-stage sampling universe. First, a regression model was applied to the relationship between the proportion of infested trunk shoot leaves and the mean density of trunk shoot leaves. This allowed the translation of a critical density for entering the vineyard in an adaptive management (AM) program into a critical proportion. A sequential binomial sampling plan was developed to efficiently decide whether a vineyard should be included into the AM program or not. Second, the spatial distribution in the entire vine plant canopy was analysed. Since there were significant differences between densities on trunk shoots and productive shoots, two different sampling plans were designed. However, there were no significant differences between other strata (parts of the vineyard, leaf position within shoots), so that they were disregarded in sampling plan design. The mean crowding - mean regression model, with the intercept set to 0, indicated aggregated distributions at the vineyard, shoot type and shoot levels. On the basis of this statistics, enumerative and sequential sampling plans are proposed and implemented in the AM framework. The here presented sampling techniques are advantageous over the previously used beating tray method and the sampling plans are useful for research and management purposes.

Resume Cette etude d'equivalence randomisee en ouvert a compare l'efficacite et la tolerance cliniques d'une nouvelle forme galenique de josamycine, comprime dispersible dose a 1 g, administree a la posologie de 2 g/j en deux prises pendant 5 jours ou pendant 10 jours, a celles d'azithromycine administree a la posologie de 500 mg le premier jour en une seule prise puis de 250 mg pendant les 4 jours suivants, au cours de la bronchite aigue survenant chez l'adulte sain (n = 472) et chez le sujet presentant une bronchite chronique (n = 51). En intention de traiter, 523 patients inclus ont ete analyses pour l'efficacite clinique en fin de traitement (J7 ou J12) (JOS 5 jours = 174; AZI 5 jours = 175; JOS 10 jours = 174), 466 ont ete analyses a distance du traitement (J30). L'analyse de la tolerance a concerne 521 patients. En fin de traitement, le pourcentage de succes cliniques a ete de 90,2 % (157/174) dans le groupe JOS 5 jours, de 91,4 % (160/175) dans le groupe AZI 5 jours et de 92,5 % (161/174) dans le groupe JOS 10 jours (resultats equivalents). A distance, il y a eu 2 rechutes sur 152 patients (1,3 %) dans le groupe JOS 5 jours, 3/158 (1,9 %) dans le groupe AZI 5 jours et 5/156 (3,2 %) dans le groupe JOS 10 jours (resultats equivalents). Un effet indesirable a ete note chez 30/173 patients du groupe JOS 5 jours, chez 24/175 patients du groupe AZI 5 jours et chez 38/173 patients du groupe JOS 10 jours (p = 0,12). Chez 10 patients seulement, l'apparition d'un evenement intercurrent a motive l'arret du traitement. L'efficacite clinique de la josamycine comprime dispersible pendant 5 jours a ete equivalente a celle de l'azithromycine pendant 5 jours et a celle de la josamycine comprime dispersible pendant 10 jours au cours de la bronchite aigue de l'adulte. Que ce soit pendant 5 jours ou pendant 10 jours, la josamycine comprime dispersible a ete aussi efficace et bien toleree que l'azithromycine pendant 5 jours.