Diagnostic performance of &supl;⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.

Assessment of primary health care: health professionals’ perspective

Objective To assess primary health care attributes of access to a first contact, comprehensiveness, coordination, continuity, family guidance and community orientation. Method An evaluative, quantitative and cross-sectional study with 35 professional teams in the Family Health Program of the Alfenas region, Minas Gerais, Brazil. Data collection was done with the Primary Care Assessment Tool - Brazil, professional version. Results Results revealed a low percentage of medical experts among the participants who evaluated the attributes with high scores, with the exception of access to a first contact. Data analysis revealed needs for improvement: hours of service; forms of communication between clients and healthcare services and between clients and professionals; the mechanism of counter-referral. Conclusion It was concluded that there is a mismatch between the provision of services and the needs of the population, which compromises the quality of primary health care.




Analysis of susceptibility to human immunodeficiency virus 1 (HIV-1) by comparative genetics

Summary [résumé français voir ci-dessous] From the beginning of the 20th century the world population has been confronted with the human immune deficiency virus 1 (HIV-1). This virus has the particularity to mutate fast, and could thus evade and adapt to the human host. Our closest evolutionary related organisms, the non-human primates, are less susceptible to HIV-1. In a broader sense, primates are differentially susceptible to various retrovirus. Species specificity may be due to genetic differences among primates. In the present study we applied evolutionary and comparative genetic techniques to characterize the evolutionary pattern of host cellular determinants of HIV-1 pathogenesis. The study of the evolution of genes coding for proteins participating to the restriction or pathogenesis of HIV-1 may help understanding the genetic basis of modern human susceptibility to infection. To perform comparative genetics analysis, we constituted a collection of primate DNA and RNA to allow generation of de novo sequence of gene orthologs. More recently, release to the public domain of two new primate complete genomes (bornean orang-utan and common marmoset) in addition of the three previously available genomes (human, chimpanzee and Rhesus monkey) help scaling up the evolutionary and comparative genome analysis. Sequence analysis used phylogenetic and statistical methods for detecting molecular adaptation. We identified different selective pressures acting on host proteins involved in HIV-1 pathogenesis. Proteins with HIV-1 restriction properties in non-human primates were under strong positive selection, in particular in regions of interaction with viral proteins. These regions carried key residues for the antiviral activity. Proteins of the innate immunity presented an evolutionary pattern of conservation (purifying selection) but with signals of relaxed constrain if we compared them to the average profile of purifying selection of the primate genomes. Large scale analysis resulted in patterns of evolutionary pressures according to molecular function, biological process and cellular distribution. The data generated by various analyses served to guide the ancestral reconstruction of TRIM5a a potent antiviral host factor. The resurrected TRIM5a from the common ancestor of Old world monkeys was effective against HIV-1 and the recent resurrected hominoid variants were more effective against other retrovirus. Thus, as the result of trade-offs in the ability to restrict different retrovirus, human might have been exposed to HIV-1 at a time when TRIM5a lacked the appropriate specific restriction activity. The application of evolutionary and comparative genetic tools should be considered for the systematical assessment of host proteins relevant in viral pathogenesis, and to guide biological and functional studies. Résumé La population mondiale est confrontée depuis le début du vingtième siècle au virus de l'immunodéficience humaine 1 (VIH-1). Ce virus a un taux de mutation particulièrement élevé, il peut donc s'évader et s'adapter très efficacement à son hôte. Les organismes évolutivement le plus proches de l'homme les primates nonhumains sont moins susceptibles au VIH-1. De façon générale, les primates répondent différemment aux rétrovirus. Cette spécificité entre espèces doit résider dans les différences génétiques entre primates. Dans cette étude nous avons appliqué des techniques d'évolution et de génétique comparative pour caractériser le modèle évolutif des déterminants cellulaires impliqués dans la pathogenèse du VIH- 1. L'étude de l'évolution des gènes, codant pour des protéines impliquées dans la restriction ou la pathogenèse du VIH-1, aidera à la compréhension des bases génétiques ayant récemment rendu l'homme susceptible. Pour les analyses de génétique comparative, nous avons constitué une collection d'ADN et d'ARN de primates dans le but d'obtenir des nouvelles séquences de gènes orthologues. Récemment deux nouveaux génomes complets ont été publiés (l'orang-outan du Bornéo et Marmoset commun) en plus des trois génomes déjà disponibles (humain, chimpanzé, macaque rhésus). Ceci a permis d'améliorer considérablement l'étendue de l'analyse. Pour détecter l'adaptation moléculaire nous avons analysé les séquences à l'aide de méthodes phylogénétiques et statistiques. Nous avons identifié différentes pressions de sélection agissant sur les protéines impliquées dans la pathogenèse du VIH-1. Des protéines avec des propriétés de restriction du VIH-1 dans les primates non-humains présentent un taux particulièrement haut de remplacement d'acides aminés (sélection positive). En particulier dans les régions d'interaction avec les protéines virales. Ces régions incluent des acides aminés clé pour l'activité de restriction. Les protéines appartenant à l'immunité inné présentent un modèle d'évolution de conservation (sélection purifiante) mais avec des traces de "relaxation" comparé au profil général de sélection purifiante du génome des primates. Une analyse à grande échelle a permis de classifier les modèles de pression évolutive selon leur fonction moléculaire, processus biologique et distribution cellulaire. Les données générées par les différentes analyses ont permis la reconstruction ancestrale de TRIM5a, un puissant facteur antiretroviral. Le TRIM5a ressuscité, correspondant à l'ancêtre commun entre les grands singes et les groupe des catarrhiniens, est efficace contre le VIH-1 moderne. Les TRIM5a ressuscités plus récents, correspondant aux ancêtres des grands singes, sont plus efficaces contre d'autres rétrovirus. Ainsi, trouver un compromis dans la capacité de restreindre différents rétrovirus, l'homme aurait été exposé au VIH-1 à une période où TRIM5a manquait d'activité de restriction spécifique contre celui-ci. L'application de techniques d'évolution et de génétique comparative devraient être considérées pour l'évaluation systématique de protéines impliquées dans la pathogenèse virale, ainsi que pour guider des études biologiques et fonctionnelles

O Processo de Raciocínio na Teoria dos Constrangimentos Aplicado numa Instituição de Ensino Superior

A Teoria dos Constrangimentos (TOC) ou das Restrições tem-se mostrado uma valiosa ferramenta de gestão, auxiliando na identificação dos constrangimentos que limitem a capacidade das empresas na prossecução da sua meta. Assim, para as restrições não físicas, a TOC desenvolveu o Processo de Raciocínio que é composto por ferramentas de análise lógica que dão subsídios para o diagnóstico de problemas bem como a formulação de soluções e planos de acção para implementá-las. Neste contexto, este trabalho se propõe a determinar a adequação do Processo de Raciocínio da Teoria dos Constrangimentos numa Instituição de Ensino Superior (IES) como forma de diagnosticar os problemas e propor soluções capazes de permitir a empresa uma melhoria contínua do seu desempenho. Serão avaliadas as ferramentas que compõem o Processo de Raciocínio, que são: Árvore de Realidade Actual, Diagrama de Dispersão de nuvens, Árvore de Realidade Futura, Árvore de Pré-Requisitos e Árvore de Transição. O trabalho inicia-se com uma pesquisa bibliográfica seguida de uma pesquisa de campo e finalizando com uma aplicação do PR numa IES localizada na ilha de São Vicente. A colecta de informações para a análise processou-se mediante a aplicação de um questionário fechado aos discentes e funcionários, questionário aberto aos docentes e entrevista estruturada aos dirigentes, elaborados em coerência com os objectivos que este estudo pretende atingir. Os resultados da aplicação do método aqui apresentado permitiram chegar as conclusões apontadas no capítulo final deste trabalho The Theory of Constraints (TOC) or Restriction Theory has proved to be a valuable management tool, assisting in the identification of constraints that restrict the ability of companies in the pursuit of its goals. Therefore, for the nonphysical constraints, TOC developed the Thinking Process (TP) that consists of logical analysis tools that provide a basis for diagnosing problems and formulating solutions and action plans to implement them. This study aims, thus, to determine the suitability of the use of the Thinking Process of the Theory of Constraints in a Higher Education Institution (HEI) as a way to diagnose problems and propose solutions that enable the firm to continually improve their performance. We will evaluate the tools that make up the TP, which are: Current Reality Tree, Evaporating Cloud Diagram, Future Reality Tree, Prerequisites Tree and Transition Tree. The work starts with a literature review, followed by a field search, and finishes with an application of the reasoning process in a higher education institution, located in São Vicente. The collection of the data for the analysis was processed through the application of a closed questionnaire to students and staff, opened questionnaire to teachers and interviews to management, drafted in line with the objectives that this study aims to reach. The results of the application of the method presented here, allowed us to reach the conclusions drawn in the final chapter of this work.

Hypertension prevalence among indigenous populations in Brazil: a systematic review with meta-analysis

Abstract OBJECTIVE Evaluating the evidence of hypertension prevalence among indigenous populations in Brazil through a systematic review and meta-analysis. METHODS A search was performed by two reviewers, with no restriction of date or language in the databases of PubMed, LILACS, SciELO, Virtual Health Library and Capes Journal Portal. Also, a meta-regression model was designed in which the last collection year of each study was used as a moderating variable. RESULTS 23 articles were included in the review. No hypertension was found in indigenous populations in 10 studies, and its prevalence was increasing and varied, reaching levels of up to 29.7%. Combined hypertension prevalence in Indigenous from the period of 1970 to 2014 was 6.2% (95% CI, 3.1% - 10.3%). In the regression, the value of the odds ratio was 1.12 (95% CI, 1.07 - 1.18; p <0.0001), indicating a 12% increase every year in the probability of an indigenous person presenting hypertension. CONCLUSION There has been a constant increase in prevalence despite the absence of hypertension in about half of the studies, probably due to changes in cultural, economic and lifestyle habits, resulting from indigenous interaction with non-indigenous society.

Use of flow cytometric methods for single-cell analysis in environmental microbiology

Flow cytometry (FCM) is emerging as an important tool in environmental microbiology. Although flow cytometry applications have to date largely been restricted to certain specialized fields of microbiology, such as the bacterial cell cycle and marine phytoplankton communities, technical advances in instrumentation and methodology are leading to its increased popularity and extending its range of applications. Here we will focus on a number of recent flow cytometry developments important for addressing questions in environmental microbiology. These include (i) the study of microbial physiology under environmentally relevant conditions, (ii) new methods to identify active microbial populations and to isolate previously uncultured microorganisms, and (iii) the development of high-throughput autofluorescence bioreporter assays

IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies-A Price Comparison with Sanger Sequencing.

The molecular diagnosis of retinal dystrophies (RD) is difficult because of genetic and clinical heterogeneity. Previously, the molecular screening of genes was done one by one, sometimes in a scheme based on the frequency of sequence variants and the number of exons/length of the candidate genes. Payment for these procedures was complicated and the sequential billing of several genes created endless paperwork. We therefore evaluated the costs of generating and sequencing a hybridization-based DNA library enriched for the 64 most frequently mutated genes in RD, called IROme, and compared them to the costs of amplifying and sequencing these genes by the Sanger method. The production cost generated by the high-throughput (HT) sequencing of IROme was established at CHF 2,875.75 per case. Sanger sequencing of the same exons cost CHF 69,399.02. Turnaround time of the analysis was 3 days for IROme. For Sanger sequencing, it could only be estimated, as we never sequenced all 64 genes in one single patient. Sale cost for IROme calculated on the basis of the sale cost of one exon by Sanger sequencing is CHF 8,445.88, which corresponds to the sale price of 40 exons. In conclusion, IROme is cheaper and faster than Sanger sequencing and therefore represents a sound approach for the diagnosis of RD, both scientifically and economically. As a drop in the costs of HT sequencing is anticipated, target resequencing might become the new gold standard in the molecular diagnosis of RD.

Aplicação de um modelo de Balanced Scorecard na Clínica Medicentro: Vantagens e desvantagens

Este trabalho procura descrever uma aplicação de uma ferramenta de gestão, designada de Balanced Scorecard, numa Clínica privada. Para fundamentação de todo o trabalho, iniciamos com uma revisão bibliográfica dos diversos conceitos relacionados com o Balanced Scorecard, nomeadamente os seus componentes, os seus princípios, as suas vantagens e desvantagens, bem como também as suas diversas fases de implementação. Posteriormente, foi desenvolvido um estudo de caso numa Clínica privada, onde fizemos uma proposta de aplicação de um instrumento de gestão, neste caso o Balanced Scorecard. Para a recolha de dados, aplicámos um guião de entrevista aos responsáveis da Medicentro, um questionário aos pacientes, utilizámos documentos fornecidos pela Instituição, e ainda utilizámos a técnica da observação directa. Neste estudo, optámos por seguir uma metodologia de implementação proposta por RUSSO (2006), adaptadas às PME, onde, em primeiro lugar, fizemos uma análise da estratégia, através de um diagnóstico da situação da Clínica, e,posteriormente, uma formulação da mesma onde foram abordados a visão da Clínica, os factores críticos de sucesso e os diversos componentes do Balanced Scorecard. Nesta metodologia proposta por RUSSO, não é evidenciado o Mapa Estratégico, logo elaborámos o mesmo, e colocamo-lo nos apêndices. Os resultados obtidos com o estudo revelaram que a Clínica possui algumas insuficiências no que concerne a sua gestão, derivadas principalmente da sua situação financeira. This work seeks to describe an application of a management tool called the balanced scorecard, in a private Clinic. Strategically we began with a literature review of the various concepts related to the balanced scorecard, including its components, their principles, their advantages and disadvantages and also their several stages of implementation. On the second step, we developed a case study in a private clinic where we made a proposal for implementation of a management tool, that is, the balanced scorecard. For data collection, we have applied an interview guide to the responsible for Medicentro, a questionnaire to patients, using documents supplied by the Institution and, in addition, of a direct observation. In this study, we have followed a methodology of implementation proposed by Russo (2006), adapted SMEs, where in first place we made an analysis of the strategy through a diagnosis of the situation of the Clinic, and later a formulation of the same were addressed to Clinical view, the critical factors of success, and the various components of the balanced scorecard. This methodology proposed by Russo is not evidenced the strategic map. Therefore we elaborated the same and we have placed it in the appendices. The results obtained from the study revealed that the Clinic has some inadequacies in what concern its management because of its financial situation.

Morphometric shape analysis using learning vector quantization neural networks - an example distinguishing two microtine vole species

Closely related species may be very difficult to distinguish morphologically, yet sometimes morphology is the only reasonable possibility for taxonomic classification. Here we present learning-vector-quantization artificial neural networks as a powerful tool to classify specimens on the basis of geometric morphometric shape measurements. As an example, we trained a neural network to distinguish between field and root voles from Procrustes transformed landmark coordinates on the dorsal side of the skull, which is so similar in these two species that the human eye cannot make this distinction. Properly trained neural networks misclassified only 3% of specimens. Therefore, we conclude that the capacity of learning vector quantization neural networks to analyse spatial coordinates is a powerful tool among the range of pattern recognition procedures that is available to employ the information content of geometric morphometrics.

Characterization of a new clinical yeast species, Candida tunisiensis sp. nov., isolated from a strain collection from Tunisian hospitals.

From a collection of yeast isolates isolated from patients in Tunisian hospitals between September 2006 and July 2010, the yeast strain JEY63 (CBS 12513), isolated from a 50-year-old male that suffered from oral thrush, could not be identified to the species level using conventional methods used in clinical laboratories. These methods include matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), germ tube formation, and the use of CHROMagar Candida and metabolic galleries. Sequence analysis of the nuclear rRNA (18S rRNA, 5.8S rRNA, and 26S rRNA) and internal transcribed spacer regions (ITS1 and ITS2) indicated that the ribosomal DNA sequences of this species were not yet reported. Multiple gene phylogenic analyses suggested that this isolate clustered at the base of the Dipodascaceae (Saccharomycetales, Saccharomycetes, and Ascomycota). JEY63 was named Candida tunisiensis sp. nov. according to several phenotypic criteria and its geographical origin. C. tunisiensis was able to grow at 42°C and does not form chlamydospores and hyphae but could grow as yeast and pseudohyphal forms. C. tunisiensis exhibited most probably a haploid genome with an estimated size of 10 Mb on at least three chromosomes. Using European Committee for Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) Candida albicans susceptibility breakpoints as a reference, C. tunisiensis was resistant to fluconazole (MIC = 8 μg/ml), voriconazole (MIC = 0.5 μg/ml), itraconazole (MIC = 16 μg/ml), and amphotericin B (MIC = 4 μg/ml) but still susceptible to posaconazole (MIC = 0.008 μg/ml) and caspofungin (MIC = 0.5 μg/ml). In conclusion, MALDI-TOF MS permitted the early selection of an unusual isolate, which was still unreported in molecular databases but could not be unambiguously classified based on phylogenetic approaches.

Measuring asymmetries in brand associations using correspondence analysis

Correspondence analysis is introduced in the brand associationliterature as an alternative tool to measure dominance, for theparticular case of free choice data. The method is also used to analysedifferences, or asymmetries, between brand-attribute associations whereattributes are associated with evoked brands, and brand-attributeassociations where brands are associated with the attributes. Anapplication to a sample of deodorants is used to illustrate the proposedmethodology.

Analysis of acute brain slices by electron microscopy: A correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of antigenicity. Finally, an important feature of this approach is that the fluorescence of the GFP signal is preserved throughout the entire preparation process until the last step before electron microscopy.

Nilotinib compassionate use in advanced GIST : a retrospective analysis

Introduction: Tyrosine kinase inhibitors (TKI) have considerably improved outcome of patients with advanced GIST and extended overall survival to more than 5 years. Yet, the median progression-free survival is approximately 2 years with first-line imatinib and 24 weeks with second-line sunitinib, which calls for treatment alternatives. Nilotinib is a second-generation TKI with at least similar inhibitory activity as imatinib. A Phase I study has shown that nilotinib monotherapy has clinical activity in GIST. Methods: After failure of all available therapeutic options patients had access to nilotinib on a compassionate use (CU) programm. Nilotinib was started at a dose of 400 mg bid, with dose reduction to 400mg qd allowed in the case of toxicity. 94 pts were approved for nilotinib CU in 10 European countries. We herein present retrospective data of 42 pts from 5 European countries treated in 11 centers. Results: Median age at nilotinib treatment start was 59 years (median; range 24-79 y). 30 of 42 patients were male. Most pts had metastatic disease of gastric origin at initial diagnosis. KIT exon 11 mutations were most frequent. The median number of surgical resections was 1 (range 0-8). All pts had failed both imatinib and sunitinib before nilotinib, and few had also received additional investigational treatments. Nilotinib was well tolerated, and discontinued due to toxicity in 15% only. Median follow-up is 176 days (range 15-876 d). Nilotinib treatment duration is 75 days (median; range 3-727 d). Partial remission with nilotinib treatment was seen in 11% of pts. Median OS was 263 days (Kaplan-Meier). Conclusion: This is the largest series reported assessing efficacy of nilotinib for imatinib- and sunitinib-refractory GIST reported yet. Nilotinib displays significant clinical activity in this heavily pretreated group of pts. These results warrant further investigation of nilotinib in GIST, including its use in first or second-line treatment. Patient and data collection is ongoing, updated results will be presented.

Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.

OBJECTIVE: To validate a revision of the Mini Nutritional Assessment short-form (MNA(R)-SF) against the full MNA, a standard tool for nutritional evaluation. METHODS: A literature search identified studies that used the MNA for nutritional screening in geriatric patients. The contacted authors submitted original datasets that were merged into a single database. Various combinations of the questions on the current MNA-SF were tested using this database through combination analysis and ROC based derivation of classification thresholds. RESULTS: Twenty-seven datasets (n=6257 participants) were initially processed from which twelve were used in the current analysis on a sample of 2032 study participants (mean age 82.3y) with complete information on all MNA items. The original MNA-SF was a combination of six questions from the full MNA. A revised MNA-SF included calf circumference (CC) substituted for BMI performed equally well. A revised three-category scoring classification for this revised MNA-SF, using BMI and/or CC, had good sensitivity compared to the full MNA. CONCLUSION: The newly revised MNA-SF is a valid nutritional screening tool applicable to geriatric health care professionals with the option of using CC when BMI cannot be calculated. This revised MNA-SF increases the applicability of this rapid screening tool in clinical practice through the inclusion of a "malnourished" category.

En route to a more democratic European Union – An analysis of the communication strategies of European Citizens’ Initiatives (ECIs)

L’èxit de l’iniciativa ciutadana europea (ICE) com a instrument de democràcia directa a nivell europeu està directament relacionat amb la seva promulgació. Els ciutadans d’arreu Europa han d’estar informats sobre aquest nou mecanisme per tal que es dugui a terme, la qual cosa suposa una dificultat. Aquest estudi qualitatiu ens mostra els recursos i problemes en la divulgació de les ICE. Una anàlisi basat en entrevistes amb diferents organitzadors d’aquestes ICE que ens dona algunes idees sobre les seves estratègies de comunicació, així com l’ús d’eines de comunicació i relacions amb els mitjans de comunicació. A banda de les dificultats lingüístiques i financeres hi ha altres obstacles més específics relacionats amb l’ICE.