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analizar la evolución del proyecto «Mapa Estratégico de Atención Farmacéutica al Paciente Externo» (MAPEX) por comunidades autónomas en España, a través del análisis de los resultados de la encuesta de situación comparativa entre los años 2016 y 2021.

En el año 2015, la Sociedad Española de Farmacia Hospitalaria (SEFH) puso en marcha el Mapa Estratégico de Atención Farmacéutica al paciente Externo (MAPEX), con el propósito de adaptar la actividad que se ofrece en las consultas externas de Farmacia Hospitalaria, al nuevo contexto sanitario.

En 2021, les groupes de risque pronostiques du cancer de la vessie non infiltrant le muscle (TVNIM) de l’Association Européenne d’Urologie (EAU) ont été modifiés. L’objectif de ce travail était de proposer une validation externe de cette nouvelle classification à l’aide de la cohorte Coblance.

Evaluar cuantitativamente el efecto de la técnica manual de fisioterapia sobre el volumen endometrial y los valores del histograma en participantes infértiles.

Engraftment syndrome (ES) is a common complication after autologous hematopoietic cell transplantation (auto-HCT) whose pathophysiological substrate remains unclear. We investigated whether endothelial damage could contribute to ES. Circulating ECs-damage biomarkers were measured in plasma from patients with (ES; n= 14) or without ES (non-ES; n= 20), collected at different time points: before HCT, 5 (S5) and 10 days (S10) after HCT, and at either the ES onset (SON) or the discharge day (SDIS). Also, cultured endothelial cells (ECs) were exposed to serum samples, obtained at the same points, to evaluate changes in ECs-activation (ICAM-1, VE-Cadherin) biomarkers, the reactivity of ECs towards leukocytes, and activation of intracellular signaling proteins related to inflammation (p38MAPK) and proliferation (Erk1/2). Results showed that circulating VWF, sTNFR1 and sVCAM-1 levels were higher in ES patients at all the points assessed, especially at SON. In vitro results showed an increased ICAM-1 expression on ECs exposed to ES samples vs. non-ES samples, especially to S5, with elevated leukocyte adhesion. Also, a lower VE-Cadherin expression and an increased phosphorylation of p38MAPK and Erk1/2 proteins were observed in ECs exposed to ES vs. non-ES samples. Our results indicate that endothelial activation precedes ES development and could be one of its pathophysiological substrates.

La caractérisation moléculaire pour la recherche de biomarqueurs d'intérêt est devenue essentielle pour la prise en charge du cancer du poumon. Or il n'existe pas actuellement en France de données qui permettent de savoir quels sont les biomarqueurs recherchés ou si les panels NGS (« Next-Generation Sequencing ») sont réalisés systématiquement en routine clinique. D'autant que les évolutions du système actuel de financement dérogatoire des tests moléculaires en France suscitent des critiques et des craintes pour l’équité d'accès. L'objectif de ce travail est de décrire l'usage de ces tests en pratique courante en oncologie pour analyser d’éventuelles barrières d'accès à ces tests, qu'elles soient organisationnelles ou financières.

En France, le cancer de la vessie est le 4èmecancer le plus fréquent chez les hommes et touche plus rarement les femmes. Les données en vie réelle sur les trajectoires de soins en pratique courante portent exclusivement sur les patients ayant eu une cystectomie. De plus, cette pathologie est considérée coûteuse du fait de récidives fréquentes. Toutefois peu de données françaises décrivent ces coûts. Notre objectif est de décrire les trajectoires de soins et les coûts de prise en charge au cours de la première année suivant le diagnostic dans l'ensemble de la population de patients incidents en 2017 (comprenant les tumeurs superficielles Ta et Tis).

Depuis 2019, dans une perspective d'introduction du séquençage à très haut débit dans le parcours de soins des patients, deux premières plateformes de séquençage haut débit (SeqOIA et AURAGEN) ont été sélectionnées par le Plan France Médecine Génomique 2025 (PFMG 2025). L'objectif était de mettre à disposition des prescripteurs français, de manière équitable, trois techniques de séquençage à très haut débit : le « Whole Genome Sequencing » (WGS), le « Whole Exome Sequencing » (WES) et le « Whole Transcriptome Sequencing » (WTS) pour une liste de 61 pré-indications (cancer et maladies rares). Notre étude vise à estimer les coûts de production des techniques de séquençage à très haut débit pour chacune de ces deux plateformes.

La cirugía de reasignación de sexo masculino a femenino o vaginoplastia incluye aquellos procedimientos quirúrgicos cuyo objetivo es recrear un perineo femenino funcional y estéticamente aceptable con una formación mínima de cicatrices. La técnica de elección en nuestro centro es la vaginoplastia con inversión peneana con o sin injertos escrotales. Presentamos 4 casos diagnosticados con fístulas rectoneovaginales tratados en nuestro centro con evolución favorable. La primera paciente fue diagnosticada en el postoperatorio tardío durante las dilataciones. Se sometió a 2 intentos de reparación vaginal sin éxito. Finalmente, se realizó una colostomía temporal y un colgajo rectal. La segunda paciente fue diagnosticada 2 semanas después de la cirugía inicial debido a una dilatación agresiva, siendo tratada con una colostomía temporal y cierre por segunda intención. La tercera paciente se diagnostica en el quinto día postoperatorio, después de la extracción del taponamiento vaginal. Se indicó restricción dietética y se realizó un colgajo rectal. Una cuarta paciente fue diagnosticada durante el postoperatorio tardío, realizando una exploración quirúrgica y un colgajo de pared rectal. Las fístulas rectoneovaginales después de la cirugía de reasignación de sexo tienen una incidencia de alrededor del 2-17%, siendo el tipo más común de fístulas después de este procedimiento. La causa más común es secundaria a lesiones rectales durante la cirugía inicial. Para el manejo de estas fístulas se plantean opciones que van desde el cierre primario a las colostomías de descarga, pasando por un manejo conservador o la confección de colgajos. Se recomienda el abordaje por un equipo multidisciplinario para el diagnóstico y tratamiento de esta complicación.

Supplemental digital content is available in the text.Ring avulsions continue to be a challenge in reconstructive surgery. We conducted a retrospective study and reviewed all Urbaniak-Kay type IV degloving injuries replanted at our institution between 2011 and 2018. A systematic review of the literature was also conducted to assess the survival rates, functional, and sensibility outcomes. The results of our systematic review outline a survival rate of 79.50% (101/127). With 1 artery being repaired, 79% of the fingers survived, a value that increased to 87.50% when 2 arteries were anastomosed (P= 0.484). Statistically significant differences (P< 0.001) were found when comparing the survival rates of the fingers with 2 or more veins repaired (87%) with those with only 1 vein anastomosed (51.90%). In terms of nerve reconstruction, there was a significant difference (P< 0.001) with the 2-point discrimination test in favor of the reconstructed group when nerve reparation was done (10.80 mm ± 2.95 mm) versus when digital nerves were not repaired (15.25 mm ± 0.50 mm). Fingers after secondary procedures did not obtain better mobility. The mean total active motion in nonreoperated fingers was 221 degrees (195–270 degrees), whereas the total active motion in the cases who received secondary surgeries was 152 degrees (110–195 degrees), with statistically significant differences (P= 0.02). Therefore, we recommend attempting replantation of degloved fingers. All efforts must be done to carry out 2 vein anastomoses, and our results strongly recommend attempting at least some kind of nerve reconstruction. Secondary surgeries should be reserved for selected cases only, because of the extensive scarring in this kind of injuries. Early mobilization protocols must be encouraged to achieve a good functional result.

En France, le cancer de la vessie est le 4èmecancer le plus fréquent chez les hommes et touche plus rarement les femmes. Les données d'incidence françaises n'incluent pas de manière exhaustive les tumeurs les plus superficielles (Ta ou Tis). Par ailleurs, les données en vie réelle sur les trajectoires de soins en pratique courante portent exclusivement sur les patients ayant eu une cystectomie. Notre objectif est de décrire la population totale incidente en 2017, les caractéristiques des patients, ainsi que les trajectoires de soins à partir des données du SNDS.

We report and study the translation of exceptionally high catalytic oxygen electroreduction activities of molybdenum-doped octahedrally shaped PtNi(Mo) nanoparticles from conventional thin-film rotating disk electrode screenings (3.43 ± 0.35 A mgPt–1at 0.9 VRHE) to membrane electrode assembly (MEA)-based single fuel cell tests with sustained Pt mass activities of 0.45 A mgPt–1at 0.9 Vcell, one of the highest ever reported performances for advanced shaped Pt alloys in real devices. Scanning transmission electron microscopy with energy dispersive X-ray analysis (STEM-EDX) reveals that Mo preferentially occupies the Pt-rich edges and vertices of the element-anisotropic octahedral PtNi particles. Furthermore, by combining in situwide-angle X-ray spectroscopy, X-ray fluorescence, and STEM-EDX elemental mapping with electrochemical measurements, we finally succeeded to realize high Ni retention in activated PtNiMo nanoparticles even after prolonged potential-cycling stability tests. Stability losses at the anodic potential limits were mainly attributed to the loss of the octahedral particle shape. Extending the anodic potential limits of the tests to the Pt oxidation region induced detectable Ni losses and structural changes. Our study shows on an atomic level how Mo adatoms on the surface impact the Ni surface composition, which, in turn, gives rise to the exceptionally high experimental catalytic ORR reactivity and calls for strategies on how to preserve this particular surface composition to arrive at performance stabilities comparable with state-of-the-art spherical dealloyed Pt core–shell catalysts.

AbstractAims:Overall survival (OS) of patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is extremely poor. New therapeutic options emerge but need to establish their economic value. The objective was to describe the direct and related costs of R/M SCCHN in France.Materials and methods:We selected all adult patients treated with chemotherapy for R/M SCCHN between 1 January 2009 and 31 December 2014 from the permanent sample of the French national health insurance database (EGB). Data were analyzed from the index date (first chemotherapy) until patients’ death or 31 December 2015. “Treatment period” and “end-of-life” (EoL) (from last chemotherapy until death) were distinguished. Costs included all hospitalizations for SCCHN and ambulatory care. Costs of hospitalized and non-hospitalized adverse events (AEs) were estimated.Results:Among 267 patients identified, 85% were men, 44% had metastases at the index date and the mean age was 62.0 years (±9.9). The most common tumor location was oropharynx (29%) but 39% of patients had multiple locations. Median OS was 9.3 (95% CI: 7.9–11.8) months for the overall population. The average total direct cost per patient was €49,954, broken down into €32,908 (95% CI: 29,525–36,290) for hospitalizations and €17,047 (14,941–19,152) for ambulatory care. Main cost drivers were drug acquisition and administration (€14,538) during the treatment period (209 days on average) and palliative care (€3,750) during the EoL period (125 days). Regarding related costs, around 12% of patients received disability pensions (€1,397 per patient [624–2,171]) and sick leave payments (€1,592 [888–2,297]). “Metabolism and nutrition disorders” and “Infections and infestations” were the most expensive hospitalized AEs (€1,513 and €1,180 per patient, respectively). Febrile neutropenia was the most expensive non-hospitalized AE (€766 per patient).Conclusions:This analysis of real-world data confirms the poor prognosis of patients with R/M SCCHN and provides cost data for future economic evaluations.

•The first outbreak of avian influenza A (H5N1) detected in Argentina was in February 2023.•The analysis of HA sequences classified them in clade 2.3.4.4b circulating in America.•Epidemiological analysis suggests multiple simultaneous entries by migratory birds.•Epidemiological surveillance in exposed humans has not detected cases in Argentina.

Ulcerative colitis (UC) is an inflammatory bowel disease of autoimmune origin with an estimated prevalence in Spain of 0.39%. Current treatments for UC do not achieve high long-term efficacy. Treatment recommendations in moderate and severe disease involve drugs, but when these options fail, the alternatives are scarce, and surgery is intended to be reserved for the last option. We present the case of a 48-year-old male patient with UC for 23 years, who had failed several lines of treatment. The patient started combined therapy with tofacitinib and vedolizumab. These drugs have different mechanisms of action, achieving an immune response and reducing gastrointestinal inflammation. The patient’s disease symptoms improved 11 months after starting this treatment, and he is now entirely asymptomatic. Analytical parameters related to the disease have also shown improvement, and the patient has so far avoided the need for surgical intervention.

Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro. We discovered characteristic patterns of hierarchical recruitment and coordinated biochemical activities that were specific for DNA structures modeling UFBs arising at either centromeres or common fragile sites. Our results describe a mechanistic model for how unresolved DNA replication structures are processed by DNA-structure-specific binding factors in mitosis to prevent pathological chromosome nondisjunction. Single-molecule and biochemistry approaches are used to investigate how ultra-fine DNA bridges, which form between sister chromatids during anaphase, are recognized and processed by cellular factors PICH, BLM, TopoIIIα and RPA.

Les méthodes de costinghospitalier nécessitent d’avoir recours à des sources de données diverses, que l’on travaille selon une approche micro-costing ou gross-costing, le choix de la méthodologie reposant sur un compromis entre coût de recueil, précision et transférabilité. Ce travail décrit les sources de données disponibles en France, les modalités d’accès pratiques ainsi que les principaux avantages et inconvénients : (1) des coûts unitaires locaux, (2) de la comptabilité analytique hospitalière, (3) de la base d’Angers, (4) de l’Étude nationale des coûts, (5) des bases de données inter CHR/U, (6) du programme de médicalisation des systèmes d’information, (7) des bases de données de l’Assurance Maladie.

The question of what monetary value should be assigned to consumed resources, that is to say the choice of the unit cost, is a major consideration in terms of impact on the cost analysis results. To date, no agreement has been reached regarding this methodological question. The choices made by methodologists and the subsequent impact on the results of the analysis are only rarely put forward. This work addresses the theoretical framework of health strategy evaluations that can be carried out either in the normative framework of the conventional economic approach of well-being, referred to as welfarist, or in that of an approach referred to as extra-welfarist. It also provides elements that help clarify the choice of the hospital unit costs used to calculate the cost of health strategies, so as to reconcile the use of such studies and improve their comparability. What is preferable, opting for specific per hospital unit costs or applying a standard unit cost to all facilities? How should a standard cost be calculated? Is it appropriate to calculate an average of the unit costs, as recommended by certain guidelines? The advantages and the limitations of the various modes of assessing hospital resources in the setting of multicentric trials are discussed.

En cancérologie, comme dans d’autres domaines de la médecine, les essais cliniques multicentriques internationaux sont nés de la nécessité de pouvoir recruter un nombre de sujets suffisants pour pouvoir étudier une question clinique. L’existence de contraintes budgétaires fortes et le souci d’allouer au mieux les ressources disponibles ont favorisé le développement des évaluations économiques associées à ces essais qui fournissent un matériel pertinent en raison de leur niveau de preuve et de leur taille. Ces évaluations posent des questions méthodologiques spécifiques tant concernant le recueil des données économiques que leur analyse. En effet, les coûts des biens et services consommés, les types et les quantités de ressources, ainsi que les pratiques médicales varient d’un pays à l’autre et au sein d’un pays. Disposer de données économiques multinationales doit permettre d’étudier et de prendre en compte cette variabilité, mais il importe d’utiliser les techniques de recueil, d’estimation des coûts et d’analyse adéquates pour agréger les résultats issus de plusieurs pays. À partir d’une revue de la littérature, l’objectif de ce travail était de faire un point méthodologique sur les spécificités liées à la réalisation d’une évaluation économique dans le cadre d’un essai clinique international : l’analyse des données d’efficacité issues de plusieurs pays, la collecte des ressources consommées, les modalités de valorisation monétaire des ressources, l’estimation des résultats agrégés en prenant en compte l’effet pays.

La cystectomie totale (CT) est le traitement de référence des patients atteints de TVIM-HR en France. Aucune donnée française relative à ces patients n’est disponible, notamment au stade adjuvant. Les objectifs de cette étude étaient de décrire les caractéristiques et la prise en charge des patients atteints d’une TVIM-HR ayant eu une CT et d’estimer leur survie sans maladie (SSM) et leur survie globale (SG).

ensure a good quality of life in the last phase of onco-hematological patients should be the primary goal, despite this, we have little data at European level and published studies are contradictory. Nevertheless, most of them agree saying that administrating chemotherapy near the end of life impacts negatively in the patients quality of life. The main objective of this study is to analyze the treatment non-aggressiveness parameters in onco-hematological patients. The secondary objective is to do a describing study of the clinical variables of the patients who receive chemotherapy at the end of life and the treatments more used.

The past decade has witnessed a significant improvement in speaker recognition (SR) technology in terms of performance with the introduction of the i-vectors framework. Despite these advances, the performance of SR systems considerably suffers in the presence of acoustic nuisances and variabilities. In this paper, we develop a data-driven nuisance compensation technique in the i-vector space without referring to the effects of the targeted nuisances in the temporal domain. This approach is nonparametric as it does not suppose a specific relationship between a “good” version of an i-vector and its corrupted version. Instead, our algorithm models directly the joint distribution of both representations (the good i-vector and its corrupted version) and takes advantage of the reproducibility of acoustic corruptions to generate the corrupted i-vectors. We then build an MMSE estimator that computes an improved version of a corrupted test i-vector, given this joint distribution. Experiments are carried out on NIST SRE 2010 and speakers in the wild databases where the proposed algorithm is used to deal with additive noise and short utterances. Our technique is shown to be efficient, improving the baseline system performance in terms of equal-error rate by up to 70% when used on known test noises and up to 65% in the context of unseen noises using a generic model. It was also proven efficient in the context of duration mismatch reaching up to 40% of relative improvement when used on short utterances using multiple models corresponding to different durations and up to 36% when used on arbitrary duration test segments.

La reconstrucción mamaria microquirúrgica con tejido autólogo puede asociar complicaciones relacionadas con el colgajo y la zona donante. Nuestro objetivo fue valorar la evidencia clínica en seguridad, complicaciones y factores de riesgo en pacientes reconstruidas con colgajo de perforantes basado en la arteria epigástrica inferior profunda (DIEP). Se realizó una revisión sistemática en Medline de artículos publicados entre septiembre de 1995 y septiembre de 2015. Se recogieron las características demográficas de las pacientes, las medidas de los colgajos y las complicaciones de la cirugía incluyendo la necrosis completa, la necrosis parcial y la necrosis grasa. Se identificaron 34 artículos que incluían 35 series de casos, 2.761pacientes y un total de 3.927colgajos. La media del índice de masa corporal fue superior a 24,5kg/m2, mientras que la tasa de obesidad se situó por encima del 14,5%. Ningún artículo aportó información acerca del peso, superficie o volumen del colgajo tras su tallado en la zona receptora. Las tasas de necrosis completa y parcial fueron del 1,9% (75/3.811) y del 2,6% (68/2.575) respectivamente. La necrosis grasa se diagnosticó en el 8,2% (308/3.746) de los colgajos, con una desviación estándar de 6,9. El 5,5% (107/1.940) de los colgajos requirieron reintervención quirúrgica. La incidencia de hematoma en la zona receptora y de hernia o debilidad abdominal fue de un 3% (59/1.952 colgajos y 52/1.725 pacientes). En conclusión, la incidencia de complicaciones en reconstrucción mamaria con colgajo DIEP fue baja, aunque la necrosis grasa presentó una dispersión elevada.

Most acute intestinal diseases are caused by food-borne pathogens. A fast and simple real-time PCR-based procedure for simultaneous detection of food contamination by any of the five food-borne pathogens: Campylobacter jejuni, Mycobacterium bovis, Enterobacter sakazaki, Shigella boydii, Clostridium perfrigens using multiplex EvaGreen real-time PCR for LightCycler was developed and evaluated. Real-time qPCR showed excellent sensitivity. Tm calling and Melting Curve Genotyping (MCG) were used for analysis of PCR product melting curves. The Melting Curve Genotyping option showed good performance for discrimination of positive samples containing DNA of single pathogen or pathogen mixtures from negative samples.

To analyze the interaction between acenocoumarol and levofloxacin in the elderly. We also assessed how hypoalbuminemia affects international normalized ratio variation.

This work aims to support real-world studies of immunotherapy-related adverse events (irAEs). Our objective was to examine whether severe irAEs could be identified in the PMSI, using data collected as part of the Registry of Severe Adverse Reactions to Immunomodulatory Antibodies used in Oncology (REISAMIC).

Supplemental Digital Content is available in the text.

Si les technologies de séquençage à haut débit (Next-Generation Sequencing[NGS]) révolutionnent la médecine, l’estimation de leur coût de production en vue de leur tarification par les systèmes de santé pose des questions méthodologiques. L’objectif de cette revue des études de coût des analyses NGS est de tirer des enseignements pour produire des estimations robustes du coût de ces techniques. Nous avons analysé selon une grille d’analyse comportant onze items les études de coûts de type micro-costingdes analyses NGS (n=17) dont deux études menées en France. Les facteurs de variabilité entre les études que nous avons identifiés sont la temporalité (évaluation précoce de l’innovation vs évaluation d’une technologie mature), le choix de la méthode d’évaluation des coûts (périmètre, technique de micro-versusgross-costing), le choix des étapes de production observées et la transposabilité de ces études. Les enseignements que nous en retirons sont qu’il faut avoir une vision globale du processus de production du séquençage en intégrant toutes les étapes depuis le prélèvement de l’échantillon biologique jusqu’au rendu du résultat au clinicien. Il importe également de distinguer ce qui relève du contexte local de ce qui relève du contexte plus général en privilégiant le recours à des méthodes mixtes pour le calcul des coûts. Enfin, des analyses de sensibilité et une ré-estimation périodique des coûts des techniques doivent être effectuées pour pouvoir réviser les tarifs en fonction des évolutions liées à la diffusion de la technologie et au jeu de la concurrence entre les fournisseurs de réactifs.

Analyse the evolution of the MAPEX Project (Strategic Map of Pharmaceutical Care for Outpatients) by regions in Spain, through the results of the comparative situation survey between the years 2016 and 2021.

In this study, flexible textile supercapacitors were obtained on jute fabrics. Insulating jute fibers were converted into electrically conducting using an optimized reduced graphene oxide (rGO) deposition method. Supercapacitors were made of jute fabric and polypyrrole (PPy) as conducting polymer. rGO improved the electrical behavior of PPy-jute supercapacitors obtained by chemical polymerization. These chemical PPy-jute supercapacitors presented a low surface resistivity (6 Ω/sq) suitable for subsequent electrochemical polymerization. The best results were obtained for rGO-PPy-jute supercapacitors synthesized by electrochemical polymerization, with capacitance values of 5127 mF cm−2(117 F g−1) in a 3-electrode system; and1770 mF cm−2, 39.9 F g−1, 250 μW h cm−2and 1100 μW cm−2in a 2-electrode system. It is essential to highlight that the jute supercapacitors obtained are eco-friendly, low cost, flexible and with very competitive energy-storage values compared to recent investigations.

Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure.

In this work, we analyze two Mn50Ni50-xSnx alloys with Sn content i.e., x = 5 and 7.5 respectively. These alloys are produced as ribbon-shape by melt spinning. Their structural transformation is checked by calorimetry. Martensitic transformation temperatures of these alloys strongly depend on the composition. From X-ray diffraction analysis, the 14M monoclinic phase is the main phase in both alloys, but in the alloy Sn5 appears a minor tetragonal phase too.

Sudden cardiac death is an unresolved problem which causes significant mortality and morbidity in both the community and in-hospital setting. Cardiac arrest is often caused by ventricular tachyarrhythmias which may be mostly interrupted by cardioversion or defibrillation. The single most critical factor for survival is the response time. Over the last 30 years, there have been virtually no procedural changes in the way hospitals address in-hospital resuscitation. A unique device has been developed that eliminates human intervention and assures defibrillation therapy is administered in seconds. This is accomplished with a fully automatic, external bedside monitor defibrillator designed to be prophylactically attached to hospitalized patients at risk of ventricular tachyarrhythmia. The safety and efficacy of the device has been demonstrated in multicenter US and European trials. Thus, this device allows a new scenario which may increase survival and enables meaningful redistribution of health resources.

The application of distributed systems theory to the implementation of industrial control systems is one of the best options to develop simple, scalable and physically distributed control systems.

A distributed expert system has been proposed for the smart house control. Its configuration is mainly based on the use of distributed nodes connected by means of a CAN network. This kind of systems allow the implementation of highly flexible control systems capable of adapting themselves to different situations. The expert system used is based on Rule Nets (RN), which are a formalism that seeks to express an automatism in a similar way to as would make it a human being: "IF antecedents THEN consequents". But at the same time Rule nets are a tool for the design, analysis and implementation of rule based systems (RBS), and consist on a mathematic-logical structure which analytically reflects the set of rules that the human expert has designed. Additionally, the RN is able to take decisions concerning possible malfunctions and has bounded response time.

To evaluate the possible involvement of adenosine A2Areceptor‐mediated mechanisms in levodopa‐induced motor fluctuations, we investigated the effects of CSC (8‐(3‐chlorostryryl) caffeine), a selective adenosine A2Areceptor antagonist, on levodopa‐induced motor alterations in rats with unilateral 6‐OHDA lesion. Acute and chronic administration of CSC was studied to evaluate the possible reversion or prevention of these levodopa effects. In a first set of experiments, rats were treated with levodopa (25 mg/kg with benserazide, twice daily, i.p.) for 22 days and on day 23 CSC (5 mg/kg, i.p.) was administered immediately before levodopa. In a second set of experiments, rats were treated daily for 22 days with levodopa and CSC (5 mg/kg/day, i.p.). The duration of the rotational behavior induced by chronic levodopa decreased after 22 days (P< 0.05). Acute administration of CSC on day 23 reversed levodopa‐induced shortening in motor response duration (P< 0.01). Chronic CSC administration did not prevent the shortening in response duration induced by levodopa. Our results demonstrate that the adenosine A2Areceptor antagonist CSC reverses but does not prevent levodopa‐induced motor alterations in parkinsonian rats. These results suggest a role for adenosine A2Areceptor‐mediated mechanisms in the pathophysiology of levodopa‐induced motor response complications. These findings suggest that the antagonism of adenosine A2Areceptors might confer clinical benefit to parkinsonian patients under levodopa therapy suffering from motor complication syndrome. Synapse 46:251–257, 2002. © 2002 Wiley‐Liss, Inc.

To evaluate the possible involvement of glutamate AMPA receptor‐mediated mechanisms in levodopa‐induced motor fluctuations, we investigated the effects of LY293558, a competitive AMPA receptor antagonist, on levodopa‐induced motor alterations in rats with unilateral 6‐OHDA lesion. Acute and chronic administration of LY293558 was studied to evaluate the possible reversion or prevention of these levodopa effects. In the first set of experiments, rats were treated with levodopa (25 mg/kg with benserazide, twice daily, i.p.) for 22 days and on day 23 LY293558 (5 mg/kg, i.p.) was administered immediately before levodopa. In the second set of experiments, rats were treated daily for 22 days with levodopa and LY293558 (5 mg/kg, twice daily, i.p.). In the third set of experiments, the effect of LY293558 (5 mg/kg, i.p.) administration on selective dopamine D‐1 (SKF38393, 1.5 mg/kg, s.c.) and D‐2 agonist (quinpirole, 0.1 mg/kg, i.p.)‐induced rotational behavior after daily levodopa treatment was studied. The duration of the rotational behavior induced by chronic levodopa decreased by 30% after 22 days. Acute administration of LY293558 on day 23 reversed this effect. The group of animals that were chronically treated with levodopa and LY293558 did not show the decrease in this motor response duration. Chronic levodopa treatment attenuated the rotational response to the D‐1 agonist SKF38393 and increased the response to the D‐2 agonist quinpirole. LY293558 did not reverse the effect of levodopa on rotational behavior induced by the D‐1 agonist but significantly reduced the rotational response to the D‐2 agonist in levodopa‐treated animals by 40%. Our results demonstrate that an AMPA receptor antagonist reverses and prevents levodopa‐induced motor alterations in parkinsonian rats and that this effect on motor fluctuations induced by chronic levodopa is probably due to a modulation of the indirect output pathway of the basal ganglia. Synapse 42:40–47, 2001. © 2001 Wiley‐Liss, Inc.

Chronic dopaminomimetic administration to parkinsonian animal models or Parkinson's disease patients leads to characteristic alteration in motor response. Previous studies suggested that the nonphysiologic stimulation of dopaminergic receptors on striatal medium spiny neurons enhances the synaptic efficacy of juxtaposed glutamate receptors of the N‐methyl‐D‐aspartate (NMDA) subtype. Resultant NMDA receptor sensitization due to differential changes in subunit phosphorylation appears to favor alterations in striatal output in ways that influence motor function. To detail the involvement of NMDA receptors further as well as to determine whether similar functional changes might develop in α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptors, the effects of selective antagonist of AMPA receptors (6‐nitro‐7‐sulfamoyl‐benzo[f]‐quinoxaline‐2,3 (1H,4H)‐dione sodium salt, NBQX, 10 mg/kg) on levodopa‐induced response alterations in 6‐hydroxydopamine (6‐OHDA) lesioned rats were compared with drugs which act competitively (3‐(±)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonicacid, CPP, 6.25 mg/kg) or noncompetitively (dextromethorphan, 40 mg/kg) to block NMDA receptors, or a nonselective inhibitor of glutamatergic transmission (2‐amino‐6‐trifluoromethoxy benzothiazole, riluzole, 5 mg/kg). We found that the shortened duration of the motor response to levodopa, which underlies human wearing‐off fluctuations, was reversed to a similar degree by the acute coadministration of CPP, NBQX, or riluzole (n = 4–6) but dextromethorphan did not. These observations strengthen the possibility that a reduction in levodopa‐associated changes in motor response by inhibitors of glutamatergic transmission acting generally or selectively at the glutamate binding‐sites may relate to their ability to attenuate pathologic gain in striatal glutamatergic function. The capacity of NBQX to reverse these altered responses suggests that an enhanced synaptic efficacy of striatal AMPA receptors may also participate in the generation of these motor response changes in levodopa‐treated parkinsonian rats. Synapse 36:267–274, 2000. © 2000 Wiley‐Liss, Inc.

Chronic dopaminomimetic administration to parkinsonian animal models or Parkinson's disease patients leads to characteristic alteration in motor response. Previous studies suggested that the nonphysiologic stimulation of dopaminergic receptors on striatal medium spiny neurons enhances the synaptic efficacy of juxtaposed glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. Resultant NMDA receptor sensitization due to differential changes in subunit phosphorylation appears to favor alterations in striatal output in ways that influence motor function. To detail the involvement of NMDA receptors further as well as to determine whether similar functional changes might develop in α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, the effects of selective antagonist of AMPA receptors (6-nitro-7-sulfamoyl-benzo[f]-quinoxaline-2,3 (1H,4H)-dione sodium salt, NBQX, 10 mg/kg) on levodopa-induced response alterations in 6-hydroxydopamine (6-OHDA) lesioned rats were compared with drugs which act competitively (3-(±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonicacid, CPP, 6.25 mg/kg) or noncompetitively (dextromethorphan, 40 mg/kg) to block NMDA receptors, or a nonselective inhibitor of glutamatergic transmission (2-amino-6-trifluoromethoxy benzothiazole, riluzole, 5 mg/kg). We found that the shortened duration of the motor response to levodopa, which underlies human wearing-off fluctuations, was reversed to a similar degree by the acute coadministration of CPP, NBQX, or riluzole (n = 4–6) but dextromethorphan did not. These observations strengthen the possibility that a reduction in levodopa-associated changes in motor response by inhibitors of glutamatergic transmission acting generally or selectively at the glutamate binding-sites may relate to their ability to attenuate pathologic gain in striatal glutamatergic function. The capacity of NBQX to reverse these altered responses suggests that an enhanced synaptic efficacy of striatal AMPA receptors may also participate in the generation of these motor response changes in levodopa-treated parkinsonian rats. Synapse 36:267–274, 2000. © 2000 Wiley-Liss, Inc.

Fredouille, Corinne, Bonastre, Jean-François, and Merlin, Teva, AMIRAL: A Block-Segmental Multirecognizer Architecture for Automatic Speaker Recognition, Digital Signal Processing10(2000), 172–197.