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Summary Background No consensus exists on how to reduce oral corticosteroids after the initiation of biologics in severe asthma. The PONENTE trial evaluated the effectiveness and safety of a rapid, individualised steroid-reduction algorithm, including adrenal insufficiency monitoring, after benralizumab initiation. Methods This multicentre, open-label, single-arm study was done at 138 clinical asthma treatment centres across 17 countries. We enrolled adult patients (age ≥18 years) with severe, eosinophilic asthma (blood eosinophil count ≥150 cells per μL at enrolment or ≥300 cells per μL in the previous year) requiring maintenance oral corticosteroids for at least 3 months preceding enrolment. Patients received benralizumab 30 mg (subcutaneous injection) every 4 weeks for three doses, then every 8 weeks thereafter. The oral corticosteroid reduction phase began at week 4 with daily oral corticosteroid dosages reduced by 1–5 mg every 1–4 weeks depending on the starting dosage, asthma control, and adrenal function status. Adrenal function was assessed with an early morning serum cortisol measurement, followed by adrenocorticotropic hormone stimulation when required, once patients achieved a daily oral corticosteroid dosage of 5 mg/day for 4 weeks. Repeat cortisol measurements were taken for patients with evidence of adrenal insufficiency at first testing. Asthma control was assessed with the Asthma Control Questionnaire-6 (ACQ-6) weekly throughout the induction and oral corticosteroid reduction phases. The primary endpoints were the percentage of patients eliminating daily oral corticosteroids, sustained for at least 4 weeks, and the percentage achieving elimination or a daily prednisone or prednisolone dosage of 5 mg or less, for at least 4 weeks, if the reason for no further reduction was adrenal insufficiency. Safety and efficacy analyses included all patients who received at least one dose of benralizumab and were descriptive. We present results after the oral corticosteroid reduction phase; a maintenance phase is ongoing. The trial is registered with ClinicalTrials.gov , NCT03557307 . Findings Between April 1, 2018, and Sept 5, 2020, of 705 patients assessed for eligibility, 598 were recruited and all received at least one dose of benralizumab. Overall, 376 (62·88%, 95% CI 58·86–66·76) of 598 patients eliminated oral corticosteroids and 490 (81·94%, 78·62–84·94) of 598 eliminated use or achieved a dosage of 5 mg or less if the reason for stopping the reduction was adrenal insufficiency. Subgroup analysis showed that dosage reductions were achieved irrespective of baseline eosinophil count, baseline oral corticosteroid dosage, or oral corticosteroid treatment duration. Adrenal insufficiency was detected in 321 (60%) of 533 patients at first assessment and in 205 (38%) of 533 patients 2–3 months later. The safety profile was consistent with previous experience. Most patients (448 [75%] of 598) had no asthma exacerbations during the oral corticosteroid reduction phase with an annualised exacerbation rate of 0·63. Of 598 patients, 38 (6%) experienced a total of 46 exacerbations resulting in emergency department or urgent care visits or hospitalisations. Interpretation Despite a high prevalence of adrenal insufficiency, most patients with eosinophilic asthma treated with benralizumab achieved elimination of oral corticosteroids or maximal possible reduction using a personalised dosage-reduction algorithm. Funding AstraZeneca.

Regional and/or national severe asthma registries provide valuable country-specific information. However, they are often limited in scope within the broader definitions of severe asthma, have insufficient statistical power to answer many research questions, lack intraoperability to share lessons learned, and have fundamental differences in data collected, making cross comparisons difficult. What is missing is a worldwide registry which brings all severe asthma data together in a cohesive way, under a single umbrella, based on standardized data collection protocols, permitting data to be shared seamlessly. The International Severe Asthma Registry (ISAR; http://isaregistries.org/) is the first global adult severe asthma registry. It is a joint initiative where national registries (both newly created and preexisting) retain ownership of their own data but open their borders and share data with ISAR for ethically approved research purposes. Its strength comes from collection of patient-level, anonymous, longitudinal, real-life, standardized, high-quality data (using a core set of variables) from countries across the world, combined with organizational structure, database experience, inclusivity/openness, and clinical, academic, and database expertise. This gives ISAR sufficient statistical power to answer important research questions, sufficient data standardization to compare across countries and regions, and the structure and expertise necessary to ensure its continuance and the scientific integrity and clinical applicability of its research. ISAR offers a unique opportunity to implement existing knowledge, generate new knowledge, and identify the unknown, therefore promoting new research. The aim of this commentary is to fully describe how ISAR may improve our understanding of severe asthma.

Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.1 Disruption and subsequent dysregulation of gut microbiota-related immunologic processes have also been linked to disease severity and response to treatment.2.

ZnO and SnO2 thin films were deposited on glass and Polyetherimide (PEI) flexible substrates by spray pyrolysis deposition at low temperature (250 °C). The structural characterization by X-ray diffraction (XRD) reveals that PEI promotes the crystallization of ZnO and SnO2 thin films while the films deposited on glass substrate are amorphous. The physical investigations show that ZnO/PEI and SnO2/PEI have a good crystalline quality and high transparency in visible range (T>80%). Their gap energies are calculated from absorbance data (3.3 eV for ZnO and 3.72 eV for SnO2). Furthermore, the surface properties are investigated by atomic force microscopy and contact angle measurements. It is found that the ZnO/PEI film has a higher surface roughness (RMS = 20.20 nm ± 0.62 nm) compared to SnO2/PEI (RMS = 5.41 nm ± 0.16 nm). The metal oxides (ZnO and SnO2) catalysts exhibit excellent photodegradation activities under UV irradiation up to 80%. The highest activity was observed for ZnO thin films because it exhibits smaller gap energy. Furthermore, both samples show excellent photocatalytic stability.

Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait. These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant and timapiprant). Although these novel biologic agents have shown promising results in many patients with asthma and COPD who have eosinophilic airway inflammation, it is evident that not all patients respond equally well, despite similar clinical, functional, and inflammatory characteristics. This heterogeneity in treatment response is probably related to different molecular pathways or endotypes leading to eosinophilic airway inflammation, including adaptive immune pathways mediated by T helper 2 cells and innate immune pathways mediated by innate lymphoid cells. The relative contribution of these pathways in asthma and COPD is not yet clarified, and there are currently no reliable biomarkers that represent the various pathways. Therefore, there is an urgent need for easily measurable and reproducible biomarkers that are linked to underlying pathophysiologic disease mechanisms and can predict and monitor responses to novel biologic agents.

A successful deposition of undoped and Fluorine doped tin oxide (TO and FTO) nano films at relatively low temperature 250 °C on flexible substrate (Polyethyerimide) was obtained using the spray pyrolysis technique. The Fluorine doping effects on the structural, morphological and optical properties were investigated. XRD measurements permit textural characterization, and show that the films have a tetragonal polycrystalline structure. The increase of crystalline size and reduction of defects and strain with Fluorine doping improve the crystalline quality. This is may be due to the substitution of O −2 by F - . Furthermore, the structural changes of the films affected the surface roughness which became rough with the Fluorine. This was confirmed by wettability measurements. Moreover, the gap energy exhibits a slight red-shift with F-doping. The photoluminescence spectra showed that Fluorine doping increased the radiative centers, which is confirmed by structural results. The photocatalytic performance of TO and FTO nanofilms were investigated by degradation of crystal violet dye under UV radiations. Results showed that TO and FTO exhibit high photocatalytic activities, which can be enhanced by H 2 O 2 addition.

Objective To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. Methods Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. Results The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p

Introduction: Chronic inflammatory diseases predispose for development of a first pulmonary embolism ( PE). Previous studies showed that corticosteroids, which are the mainstay of treatment for inflammatory diseases, enhance the risk of a first venous thromboembolism. Yet, it is unknown whether corticosteroids also predispose for recurrent events. Therefore, we investigated the association between oral and/or inhaled corticosteroid use and the risk of recurrent PE.Methods: We performed a nested case-control study using the PHARMO Database. Adult patients who had suffered from a first PE for which vitamin K antagonists were prescribed, were eligible. Of these, 384 patients with recurrent PE were matched to 1030 patients without recurrent PE.Results: We showed that oral or inhaled corticosteroids was ever used by 22.7% and 20.6% of patients with recurrent PE, and 23.5% and 21.5% of the patients without recurrent PE. There was an overall association between oral corticosteroid use and the risk of recurrent PE (p = 0.02). Current use of oral corticosteroids increased the risk of recurrent PE (OR 3.74; 95% CI 2.04-6.87), whereas past use reduced the risk (OR 0.46; 95% CI 0.28-0.74). A similar pattern was observed for inhaled corticosteroids, although less strong (p - 0.10).Conclusions: Current use of oral corticosteroids is associated with increased risk of recurrent PE. Whether this increased risk is caused by oral corticosteroids themselves, or by the underlying disease, or both, needs further investigation. Nevertheless, given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk. (C) 2016 Elsevier Ltd. All rights reserved.

Introduction L’efficacite et la tolerance du mepolizumab dans ASE etant bien etablies, COMET a examine les resultats apres la poursuite ou l’arret du mepolizumab a long terme. Methodes COMET etait une etude multicentrique, randomisee, en double aveugle, controle par placebo. Les patients eligibles avaient complete COLUMBA/COSMEX, recu un traitement continu par mepolizumab pendant au moins 3 ans. Les patients ont ete randomises 1 :1 pour continuer mepolizumab 100 mg par voie SC toutes les 4 semaines pendant 52 semaines ou pour arreter mepolizumab. Les patients pouvaient revenir au traitement par mepolizumab en ouvert a la suite d’une exacerbation. Le critere primaire etait la duree jusqu’a la premiere exacerbation cliniquement significative. Les criteres secondaires etaient : la duree jusqu’a la diminution du controle de l’asthme ; la reduction de taux d’eosinophiles sanguins. Les criteres ont ete analyses en utilisant le modele des risques proportionnels de Cox et des modeles repetes de modele mixte ajustes pour les covariables. Resultats Cent quarante-quatre patients ont recu mepolizumab et 151 placebo. Quarante-six pour cent (66/144) patients ayant continue mepolizumab versus 59 % (89/151) patients ayant arrete mepolizumab ont eu une exacerbation. Les patients ayant continue versus ceux ayant arrete mepolizumab ont eu une duree plus longue jusqu’a la premiere exacerbation (HR : 0,62 [(IC)95 % : 0,45 ; 0,86] ; p = 0,004) et une duree significativement plus longue jusqu’a la diminution du controle de l’asthme (HR : 0,66 [0,49 ; 0,88] ; p =0,005), sans difference entre les traitements pour la duree jusqu’a la premiere exacerbation necessitant une venue aux urgences ou une consultation (HR : 1,33 [0,50 ; 3,51]). Les patients continuant mepolizumab ont maintenu leur taux d’eosinophiles entre 40 et 60 cellules/μL, les taux d’eosinophiles ont augmente jusqu’a 270 cellules/μL a la semaine 12 pour les patients ayant arrete mepolizumab (ratio : 0,19 [0,15 ; 0,24] ; p Conclusion Les patients ayant arrete mepolizumab ont presente une augmentation du taux d’eosinophiles sanguins, une augmentation des exacerbations, une duree plus courte jusqu’a la premiere exacerbation, et une reduction du controle de l’asthme compare a ceux ayant continue mepolizumab. Ces resultats montrent que le traitement continu par mepolizumab a des benefices cliniques durables chez la plupart des patients avec ASE.

Introduction La pustulose exanthematique aigue localisee (PEAL) est une entite tres rare de decouverte recente. C’est une variante localisee de la pustulose exanthematique aigue generalisee (PEAG) qui a ete longtemps rattachee a une origine purement medicamenteuse. Materiel et methodes C’est une etude retrospective colligeant tous les cas de PEAL diagnostiques cliniquement au service de dermatologie de Monastir-Tunisie sur une periode de 8 ans (juin 2011–mai 2019). Nous avons selectionne tous les cas confirmes selon les criteres diagnostiques de l’EuroSCAR. Resultats Nous avons collige 12 cas de PEAL. Tous nos patients etaient des enfants d’âge moyen 8 ans. Le sex-ratio etait de 2. Chez tous les patients, les lesions etaient apparues en printemps. La presentation clinique correspondait a la des plaques erythemato-odemateuses parsemes de pustules dans tous les cas. Les lesions etaient localisees au niveau de la face dans 91,6 %. Une atteinte concomitante de la main etait trouvee chez un malade. Les lesions etaient strictement localisees au niveau des organes genitaux externes dans un cas. Le diagnostic de PEAL etait confirme histologiquement dans 7 cas. Une enquete minutieuse avait elimine toute origine medicamenteuse systemique. Ces lesions etaient declenchees par une piqure d’insecte dans un cas et par l’application locale de benzoate de benzyle en poudre chez une autre patiente. La notion de contact avec une plante quelques heures avant l’apparition de la lesion etait trouvee dans 4 cas. Il s’agissait de Thapsia garganica dans deux cas et d’ Hordeum murinum L chez les deux autres malades. Le patch test pratique chez un patient etait positif pour Thapsia garganica. Tous nos patients avaient beneficie d’une corticotherapie locale ou generale avec une regression complete des lesions. Discussion Nous avons rapporte une serie de douze cas pediatriques de PEAL. La PEAL est une entite rare, decrite par Prange et al. en 2005. Et depuis, seulement une vingtaine de cas etait rapportee. Sur le plan clinique, il s’agit d’une variante localisee de la PEAG sans signes generaux associes. Elle partage les memes caracteristiques histologiques que la PEAG. La quasi-totalite des cas publies etaient induits par une prise medicamenteuse par voie generale. La PEAL de contact etait exceptionnellement rapportee. Le premier cas etait rapporte par une equipe algerienne suite a un contact avec une plante, Sinapis arvensis. La PEAL d’origine non medicamenteuse de contact semble etre sous-estimee. Dans notre serie, l’enquete etiologique a elimine toute cause medicamenteuse. Notre serie est particuliere par la predominance de l’atteinte faciale, le caractere saisonnier et la survenue chez des enfants, ce qui fait l’hypothese d’une exposition a des substances aeroportees d’origine vegetale, comme les pollens de certaines fleurs. Conclusion Notre serie est la plus large dans la litterature de PEAL non medicamenteuse.

Resume La bronchopneumopathie chronique obstructive (BPCO) est une maladie dyspneisante qui constitue une astreinte aux activites physiques des patients atteints. Ses repercutions mentales ne sont pas moindres et s’expriment par une alteration non negligeable de la qualite de vie. Objectifs Evaluer la qualite de vie et ses facteurs determinants chez des patients tunisiens atteints de BPCO. Patients et methodes Nous avons mene une enquete epidemiologique transversale, descriptive etalee sur une periode de 6 mois allant de janvier 2008 jusqu’a juin 2008 et qui a porte sur les patients atteints de BPCO hospitalises et suivis au service de pneumo-allergologie du CHU Farhat Hached de Sousse en Tunisie. Nous avons utilise la version francaise du questionnaire respiratoire du Saint-George Hospital (SGRQ) pour l’etude de la qualite de vie et le Hospital Anxiety Depression (HAD) pour l’exploration de l’anxiete et de la depression. Resultats Chez les 100 malades inclus dans l’etude, la moyenne du score global du SGRQ etait de 44,31 ± 13,85 %. Dix patients presentaient un etat depressif et 9 malades presentaient un etat anxieux. Les resultats de l’analyse par regression lineaire multiple ont montre que quatre facteurs etaient lies significativement plus que les autres a une alteration de la qualite de vie qui etaient : la dyspnee, le nombre d’exacerbations, la comorbidite et la depression. Conclusion L’impact psychologique et l’effet sur la qualite de vie de la BPCO sont des outils qui s’ajoutent aux donnees physiques et spirometriques lors du suivi therapeutique des malades et devraient etre systematiquement recherches par les praticiens, conduite encore rare en Tunisie.

Transit passengers’ response to crowded conditions has been studied empirically, yet is limitedly included in transport models currently used in the design of policy and infrastructure investments. This has consequences for the practical applicability of these models in studies on, for instance, timetabling, train capacity management strategies, project appraisal, and passenger satisfaction. Here we propose four methods to include the effect of crowding, based on existing studies on passengers’ perception and response as well as often-used crowding indicators. These four alternative methods are implemented in the train passenger assignment procedure of the Dutch national transport model, and evaluated with respect to their impacts on the model results for the Dutch railway network. The four methods relate to four different ways in which an additive trip penalty and/or time-multiplier can be incorporated in the train utility function for different travel purposes, to capture the disutility of crowding as measured by the load factor. The analyses of the test case favor the hybrid method using both a boarding penalty (capturing seat availability upon boarding) and a time-multiplier (capturing physical comfort and safety throughout the trip). This method produces consistent results, while the additional computational effort that it imposes is acceptable. Further empirical underpinning is needed to conclusively show which of these methods best captures passengers’ response behavior quantitatively (for different travel purposes and conditions).

Severe asthma affects fewer than 10% of patients with asthma, is associated with a severe risk of death and disability, has a great impact on health and quality of life, and represents a huge cost to patients and society. Given the poor response to treatment and the side effects associated with medications for severe asthma, more efficient, cost-effective, and phenotype-specific medications are needed. Considering severe asthma as an orphan disease could encourage the pharmaceutical industry to stratify studies based on a more detailed characterization of study subjects at baseline, resulting in the development of novel therapeutic approaches.

Introduction Le diagnostic d’une hypoglycemie spontanee en dehors du contexte du diabete peut etre difficile et souvent porte par exces. Patients et methodes Notre etude retrospective porte sur l’ensemble des malades hospitalises en vue d’une exploration d’un malaise dit « hypoglycemique » durant une annee. Les objectifs etaient de determiner la prevalence des vraies hypoglycemies. Resultats Nous avons collige 82 hospitalisations avec une duree moyenne de 6,74 ± 3,9 jours. L’hypoglycemie a ete confirmee chez 23 (28 %). Les signes adrenergiques etaient rapportes dans les deux groupes (groupe des hypoglycemies infirmees et groupe des hypoglycemies confirmees) sans differences significatives. Les signes neuroglycopeniques, decrits chez tous les patients mais les cephalees etaient le seul signe qui differe significativement entre les deux groupes (p = 0,03). Tous les patients ont beneficie d’une evaluation de la fonction renale, la fonction hepatique ainsi qu’une glycemie a jeun et un bilan lipidique. Un bilan thyroidien a ete realise dans 28 cas, une cortisolemie de base dans 45 cas et apres test au synacthene dans 25 cas. Une HGPO realisee dans 48 cas, une epreuve de jeune totale realisee chez 60 sujets. Les etiologies retenues etaient une hypoglycemie factice dans 8 cas, une hypoglycemie fonctionnelle dans 8 cas, un hyperinsulisme endogene dans 5 cas avec un insulinome confirme dans deux cas. Une insuffisance surrenalienne dans un cas et corticotrope dans 1 cas. Conclusion La symptomatologie des hypoglycemies variee et non specifique peut amener a des investigations en exces avec un cout eleve des hospitalisations.

Introduction Des observations cliniques de cancers multiples synchrones ont ete rapportes dans la litterature mais il s’agit une entite assez rare. Observation Homme âge de 57 ans, tabagique a 45 PA, adresse pour exploration d’incidentalome surrenalien bilateral decouvert a l’Uro TDM avec a droite une masse surrenalienne ovalaire bien limitee mesurant 57 × 70 mm, de densite 25 UH de rehaussement heterogene et a gauche deux nodules surrenaliens gauches mesurant 17 × 15 mm et 10 × 21 mm, de faible densite spontanee ( Conclusion Cette observation illustre la possibilite de survenue de corticosurrenalome evoluant d’une maniere synchrone avec un adenocarcinome pulmonaire, ce qui est une association assez rare.

The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.

Background: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease. Objective: This study sought to determine the remission rate and identify predictors of persistence and remission of adult-onset asthma. Methods: Two hundred adult patients with recently diagnosed ( = 1 year and no asthma medication use for >= 1 year. Descriptive statistics and logistic regression analysis were performed. Results: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps, and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these 2 characteristics had

In this contribution, an inverse identification strategy of constitutive laws for elastoplastic behaviour is presented. The proposed inverse algorithm is composed on an appropriate finite element calculation combined with an optimisation procedure. It is applied to identify material anisotropic coefficients using a set up of easy performed laboratory tests. The used experimental data are the plane tensile test and the off axes tensile tests. The identified behaviour models are mainly based on Hill's quadratic yield criterion. Two cases of this yield criterion have been considered: the transverse isotropic and the orthotropic one under an associated and non-associated flow rule assumptions for each case. The yield surface has been assumed to expand isotropically (isotropic strain hardening law) as a function of the plastic work. In order to better describe anisotropic plastic properties of the studied materials, a recently planar anisotropic yield function is used. It is a non-quadratic yield criterion which takes account of anisotropic yield stresses as well as anisotropic strain ratios. It is subsequently shown that the agreement between inverse identification results and experimental measurements were improved. We prove also that the presented strategy is a good alternative to the simplified homogeneous tests assumption, especially for the plane tensile test.

Experimental investigations on the wet batch comminution of an alumina hydrate in a stirred bead mill are presented. The influence of some operating parameters (mass solids concentration, initial size of particles, stirrer speed and beads size) on both the specific energy and the size distribution of the ground product is discussed. The existence of a limit fineness has been put in evidence and the conditions leading to a best efficiency of the process are defined. A quantitative characterization of the morphology of the fragmented particles has led to the identification of the fragmentation path occurring during the process. The analysis allows to interpret the evolution vs. time of the product size distributions characterized by a multimodal pattern.

The status of advancement of the VIRGO Project is presented: the first-generation results from the Pisa seismic noise super attenuator give an upper limit to the noise transfer function of 2 × 10 −8 at 10 Hz. The upper limit to the absolute noise of the 400 kg test mass at 10 Hz has been measured to be 1.5 × 10 −13 m/√Hz. The scheme and the related problems of the VIRGO interferometer, which is supposed to work down to 10 Hz, are also presented. At the 3rd Pisa Meeting in 1986 we presented the idea of what could be a very efficient seismic noise reduction system able to give a sensitivity h ∼ 10 −25 at 10 Hz, in a 3 km interferometer for 1 year integration time. Now we have two new facts to present: the first is that the attenuation has been built, is working in Pisa, and shows remarkable characteristics. The second is the Italian-French interferometer VIRGO [1,2], a 3 km long antenna for low and high frequency (10–1000 Hz) gravitational wave (GW) detection. These two items will be presented in this article.

This paper is focused on the grinding and dispersion of TiO2 in a stirred bead mill. Batch and continuous wet grinding experiments have been carried out and the best conditions for grinding TiO2 have been identified with respect to agitation speed, suspension flow rate, media size and filling volume. Kinetics equations, based on the linear combination of log-beta laws describing the changes of multimodal size distributions vs. grinding time have been established. A process model for continuous comminution of TiO2 has been derived. The transport of the fragmented particles was modelled by four agitated cells with backmixing. Combining this model with grinding kinetics, the product size distribution achieved by continuous grinding was calculated and compared to experimental results.

Objectif Etudier la perception de l’insulinotherapie d’un groupe de diabetiques type 2 traites par insuline et preciser les facteurs qui peuvent l’influencer. Patients et methodes Etude transversale ayant inclut 45 diabetiques de type 2 traites par insuline recrutes dans l’hopital du jour a l’institut national de nutrition de Tunis. Nous avons utilise l’echelle « Insulin Treatment Appraisal Scale : ITAS » pour evaluer la perception de nos patients du traitement par insuline. Cette echelle comprend 20 items :16 items positifs et 4 items negatifs. Elle etait traduite en arabe facile. Le score varie de 20 a 100. Plus le score est eleve plus la perception est negative. Resultats L’âge moyen de nos patients etait de 60,9 ± 5,2 ans. L’anciennete moyenne de diabete etait de 11,8 ± 8,3 annees. L’HbA1c moyenne etait de 10,5 ± 2,5 %. La duree moyenne de l’insulinotherapie etait de 4,5 ± 3,4 ans. Les deux tiers des patients etaient hypertendus et 40 % avaient une dyslipidemie. Le score moyen des 16 items negatifs etaient de 58,2 ± 5. Le score moyen des 4 items positifs etait de 12,6 ± 2,4. Le score total moyen etait de 66,7 ± 9,1. Les trois scores etaient comparables dans les deux sexes. Nous n’avons pas trouve une correlation entre l’anciennete de diabete et la duree de l’insulinotherapie d’une part et la perception de l’insulinotherapie. Par contre, les patients d’un niveau d’instruction eleve et ceux utilisant les analogues d’insuline ont un score moyen total significativement plus bas (54,4 et 55,8 ; p = 0,04). Discussion La resistance psychologique a l’insuline est un phenomene frequent et prejudiciable. Elle doit etre recherchee et prise en charge afin d’ameliorer la qualite de vie des patients diabetiques.