Present development concerning antimalarial activity of phospholipid metabolism inhibitors with special reference to in vivo activity

The systematic screening of more than 250 molecules against Plasmodium falciparum in vitro has previously shown that interfering with phospholipid metabolism is lethal to the malaria parasite. These compounds act by impairing choline transport in infected erythrocytes, resulting in phosphatidylcholine de novo biosynthesis inhibition. A thorough study was carried out with the leader compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature parasites (trophozoïtes) as determined in vitro with P. falciparum and in vivo with P. chabaudi -infected mice. This specificity corresponds to the most intense phase of phospholipid biosynthesis activity during the parasite cycle, thus corroborating the mechanism of action. The in vivo antimalarial activity (ED50) against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to 20-fold, depending on the P. berghei-strain). This difference in activity could result either from the degree of synchronism of every strain, their invasion preference for mature or immature red blood cells or from an intrinsically lower sensitivity of the P. berghei strain to G25. Irrespective of the mode of administration, G25 had the same therapeutic index (lethal dose 50 (LD50)/ED50) but the dose to obtain antimalarial activity after oral treatment was 100-fold higher than after intraperitoneal (or subcutaneous) administration. This must be related to the low intestinal absorption of these kind of compounds. G25 succeeded to completely inhibiting parasitemia as high as 11.2% without any decrease in its therapeutic index when administered subcutaneously twice a day for at least 8 consecutive days to P. chabaudi -infected-rodent model. Transition to human preclinical investigations now requires a synthesis of molecules which would permit oral absorption.

Frailty and use of health and community services by community-dwelling older men: the Concord Health and Ageing in Men Project.

BACKGROUND: frailty is a concept used to describe older people at high risk of adverse outcomes, including falls, functional decline, hospital or nursing home admission and death. The associations between frailty and use of specific health and community services have not been investigated. METHODS: the cross-sectional relationship between frailty and use of several health and community services in the last 12 months was investigated in 1,674 community-dwelling men aged 70 or older in the Concord Health and Ageing in Men study, a population-based study conducted in Sydney, Australia. Frailty was assessed using a modified version of the Cardiovascular Health Study criteria. RESULTS: overall, 158 (9.4%) subjects were frail, 679 (40.6%) were intermediate (pre-frail) and 837 (50.0%) were robust. Frailty was associated with use of health and community services in the last 12 months, including consulting a doctor, visiting or being visited by a nurse or a physiotherapist, using help with meals or household duties and spending at least one night in a hospital or nursing home. Frail men without disability in activities of daily living were twice more likely to have seen a doctor in the previous 2 weeks than robust men (adjusted odds ratio 2.04, 95% confidence interval 1.21-3.44), independent of age, comorbidity and socio-economic status. CONCLUSION: frailty is strongly associated with use of health and community services in community-dwelling older men. The high level of use of medical services suggests that doctors and nurses could play a key role in implementation of preventive interventions.

Biological comparison between three clones of Trypanosoma cruzi and the strain of origin (Bolivia) with reference to clonal evolution studies

After isolating three clones of Trypanasoma cruzi (Bolivia), we first characterized them according to parasitaemia, pleomorphism and virulence, and then histopathologically. The study's interest lies on the hypothesis that clonal evolution of T. cruzi has a major impact on biologically relevant properties of this parasite. Data obtained from the studies of parasitaemia, pleomorphism and virulence showed no differences between the groups studied. As a final point, the histopathological study shows us a muscular tissue tropism both in clones and in their mother strain (Bolivia). In this paper, we conclude that Bolivia strain and clones isolated from it, pertaining to the same major clone share similar biological properties.

Monitorització de rendiment i accounting de centres de computació grid

El Port d'Informació Científica és un centre de Computació Grid de referència que dona suport a comunitats científiques, com el LHC (CERN). Al PIC, trobem una gran varietat de tecnologies que proporcionen serveis al centre. Des de l'arquitectura i elements de la xarxa, fins a recursos informàtics de computació, sistemes d'emmagatzematge a disc i cinta magnètica, bases de dades (ORACLE/PostgreSQL). El projecte consisteix en el disseny i implementació d'una base de dades col·lectora de tota la informació rellevant dels diferents sistemes del centre, i un portal web on mostrar tots els valors i gràfiques, tot basat en programari lliure.

Services de migration et évolution de la population étrangère dans les cantons suisses 2002-2008 = Migrationsämter und Entwicklung der ausländischen Bevölkerung in den Kantonen 2002-2008

Cette étude montre que les cantons sont confrontés à une augmentation importante de la population étrangère résidante mais aussi du nombre de frontaliers et ceci surtout depuis 2004. La plupart des services cantonaux de migrations sont sous pressions malgré la simplification des formalités pour les ressortissants de l'UE. L'originalité de cette recherche tient au fait qu'elle aborde, pour la première fois, le thème de la population étrangère sous l'angle des activités administratives générées au niveau des cantons. Il s'agit également de la première évaluation présentant dans le détail l'étendue et la multiplication des tâches dévolues à l'Etat du fait de cette immigration depuis l'entrée en vigueur le premier juin 2002 de l'Accord sur la libre circulation des personnes avec l'UE (ACLP). Diese Studie zeigt, dass die Kantone mit einer starken Zunahme der ausländischen Wohnbevölkerung sowie der Zahl Grenzgänger konfrontiert sind. Vor allem seit 2004 sind die Migrationsämter der Kantone, trotz einer Vereinfachung der Formalitäten für EU Angehörige, unter Druck geraten. Die Besonderheit dieser Studie ist, dass sie zum ersten Mal das Thema der ausländischen Bevölkerung aus dem Blickwinkel der administrativen Tätigkeiten der Kantone betrachtet. Es handelt sich auch um die erste Studie, die im Detail die Mehrbelastung durch neue Aufgaben analysiert, welche der Staat auf Grund der Migration seit Inkrafttreten des Personenfreizügigkeits-abkommens (FZA) im Juni 2002 zu leisten leistet hat.

Biological Parameters and Molecular Markers of Clone CL Brener - The Reference Organism of the Trypanosoma cruzi Genome Project

Clone CL Brener is the reference organism used in the Trypanosoma cruzi Genome Project. Some biological parameters of CL Brener were determined: (a) the doubling time of epimastigote forms cultured in liver infusion-tryptose (LIT) medium at 28oC is 58±13 hr; (b) differentiation of epimastigotes to metacyclic trypomastigotes is obtained by incubation in LIT-20% Grace´s medium; (c) trypomastigotes infect mammalian cultured cells and perform the complete intracellular cycle at 33 and 37oC; (d) blood forms are highly infective to mice; (e) blood forms are susceptible to nifurtimox and benznidazole. The molecular typing of CL Brener has been determined: (a) isoenzymatic profiles are characteristic of zymodeme ZB; (b) PCR amplification of a 24Sa ribosomal RNA sequence indicates it belongs to T. cruzi lineage 1; (c) schizodeme, randomly amplified polymorphic DNA (RAPD) and DNA fingerprinting analyses were performed

An audit of diagnostic reference levels in interventional cardiology and radiology: are there differences between academic and non-academic centres?

A wide variation in patient exposure has been observed in interventional radiology and cardiology. The purpose of this study was to investigate the patient dose from fluoroscopy-guided procedures performed in non-academic centres when compared with academic centres. Four procedures (coronary angiography, percutaneous coronary intervention, angiography of the lower limbs and percutaneous transluminal angioplasty of the lower limbs) were evaluated. Data on the dose-area product, fluoroscopy time and number of images for 1000 procedures were obtained from 23 non-academic centres and compared with data from 5 academic centres. No differences were found for cardiology procedures performed in non-academic centres versus academic ones. However, significantly lower doses were delivered to patients for procedures of the lower limbs when they were performed in non-academic centres. This may be due to more complex procedures performed in the academic centres. Comparison between the centres showed a great variation in the patient dose for these lower limb procedures.

La gestion des services environnementaux: entre règles et régulation négociée. Six études de cas de services forestiers pour la production d'eau potable dans trois pays

Cette thèse est construite en quatre parties : trois annexes qui présentent six études de cas (env. 800 pages), précédées par une analyse transversale, plus synthétique (env. 150 pages), dont traite ce résumé. Chaque annexe contient une synthèse détaillée des études de cas. Cette thèse aborde la « gestion des ressources naturelles » en affirmant d'emblée que l'appellation est inappropriée, car ce ne sont pas les ressources qui sont gérées, mais leurs usages. Il s'agit donc d'identifier et d'analyser ce qui influence les comportements humains en lien avec la ressource. Cette affirmation fonde la perspective des sciences sociales sur la gestion des ressources naturelles, dans laquelle s'inscrit cette thèse. L'approche néo-institutionnaliste considère que les usages sont influencés par des institutions, qui sont elles-mêmes influencées par les usagers. Ces institutions sont des constructions humaines qui composent le contexte institutionnel dans lequel les acteurs décident de leurs usages (abattre un arbre, prélever de l'eau, etc.). Les usages des ressources ne sont donc jamais libres et il s'agit de comprendre comment ces règles du jeu influencent les pratiques. Elles sont nombreuses, interdépendantes et forment la trame sur laquelle se décident les usages. Pour saisir cette complexité, l'auteur applique le cadre d'analyse des régimes institutionnels des ressources (RIR) qui se limite à l'analyse de deux types de droits d'usages : ceux issues des règles de la propriété (titres de propriété, servitudes, etc.) et ceux issus des politiques publiques (lois, ordonnances, etc.). Le RIR permet d'identifier un « régime institutionnel », spécifique à la ressource étudiée, dont les évolutions peuvent être comparées dans le temps ou entre plusieurs lieux. Dans cette recherche, ce cadre d'analyse a été appliqué au même objet - la gestion forestière dans les zones de captage d'eau souterraine destinée au réseau public - dans trois pays : en France, en Suisse et en Indonésie. Trois années de recherche de terrain ont permis à l'auteur de s'intéresser non seulement aux règles prédéterminées (la réglementation), mais aussi aux règles effectivement activées sur le terrain (la régulation) par les acteurs rencontrés. Les études de cas montrent que les règles prévues sont inégalement activées et que les acteurs privilégient parfois la négociation directe pour résoudre leurs rivalités d'usages, à la place d'invoquer leurs droits acquis. Ce constat conduit l'auteur à proposer un élargissement de la focale du RIR, qui constitue le coeur de sa thèse. On ne s'intéresse plus seulement à ce qui « est » régulé, mais aussi à ce qui ne l'« est pas » et qui échappe à l'application classique du RIR. Ce renversement de perspective est crucial pour comprendre les usages concrets des ressources dans les régimes peu intégrés, où les pratiques s'expliquent davantage par la marge de manoeuvre laissée aux acteurs que par les règles prédéterminées. Cette relecture, testée avec succès dans cette thèse, permet d'intégrer la marge de manoeuvre à l'analyse au moyen du RIR. Elle se concrétise par l'identification des lacunes et incohérences dans les régimes institutionnels étudiés. Le champ d'application du RIR s'en trouve élargi et sa vulgarisation pour des non-spécialistes est facilitée, notamment pour les environnementalistes. La complémentarité entre les approches s'en trouve renforcée. Les résultats montrent deux choses : premièrement les acteurs disposent toujours d'une marge de manoeuvre pour négocier des régulations ponctuelles, qui sont autant d'alternatives à l'application des règles prévues. Deuxièmement, la conclusion d'accords issus de la négociation bi-/multilatérale dépend directement de la marge de manoeuvre laissée par le contexte institutionnel. Ceci explique pourquoi la négociation entre les propriétaires forestiers et les exploitants de captages s'imposent en Indonésie, est envisageable en France, mais n'aboutit pas en Suisse. Les nombreuses tentatives infructueuses de mise en oeuvre de solutions négociées, notamment sous forme de paiements pour services environnementaux (PSE), trouvent ici une explication. - This thesis (written in French) is built in four parts: three annexes that present six case studies (approx. 800 pages), preceded by a transverse, more conceptual analysis (approx. 150 pages), which this summary is about. Each annexe contains a detailed summary of the case studies. 'Natural resource management' is an inappropriate designation because it is not the resources that are managed but the uses made of them, therefore this thesis addresses the identification and analysis of the influences on human behaviour in relation to the resource. This statement roots the social sciences perspective on the management of natural resources, in which this thesis fits. A neoinstitutionalist approach considers that the uses are influenced by institutions, which are themselves influenced by users. These institutions are human constructions that form the institutional context in which the actors decide on the use of resources (felling a tree, collecting water, etc.). Thus, the uses of resources are never independent from institutional influences and it becomes necessary to understand how these rules of the game affect practices. They are numerous, interrelated and form the basis for the uses of resources. To understand this complexity, the author applies the institutional regime resource framework (IRR) which limits the analysis to two types of use rights: those resulting from the property rights (deeds, easements, etc.) and those from public policies (laws, ordinances, etc.). The IRR identifies an 'institutional regime', specific to the resource, from which developments can be compared over time or between several places. In this research, this analytical framework has been applied to the same topic - forest management in the recharging areas of groundwater piped for public supply - in three countries: France, Switzerland and Indonesia. Three years of field research allow the author to look not only at predetermined rules (rules), but also at regulations that are actually activated on the ground (rules-in-use). The case studies show that the predetermined rules are unevenly applied and that sometimes actors favour direct negotiation to resolve their rivalry of uses, instead of invoking their vested rights. From this observation the author proposes an enlargement of the IRR's scope, forming the core of his thesis. The interest covers not only what 'is' regulated, but what 'is not' and so is beyond the classical application of the IRR. This shift in perspective is crucial to understand the concrete uses of resources in poorly integrated regimes, where practices are explained by the margin of manoeuvre left to the actors rather than predetermined rules. This reinterpretation, tested successfully in this research, allows the margin of manoeuvre to be integrated in the analysis using the IRR and is made concrete by the identification of gaps and inconsistencies in the investigated institutional context. The new interpretation of the IRR in this thesis complements and enhances its classical application. In particular, its use and understanding by non-specialists, especially environmentalists, is facilitated. The results show two things: first the actors always have leeway to negotiate ad hoc regulations, which are alternatives to the application of the predefined rules. Second, the conclusion of bi/multilateral negotiated agreements depends directly on the leeway left by the institutional context. This explains why the negotiation between forest owners and operators of water catchments is needed in Indonesia, is possible in France, but does not succeed in Switzerland. This offers an explanation for many unsuccessful attempts to implement negotiated solutions, notably payments for environmental services (PES).

Health services utilization associated with cognitive impairment and dementia in older patients undergoing post-acute rehabilitation.

OBJECTIVE: To investigate the relationship between levels of cognitive impairment and health services utilization in older patients undergoing post-acute rehabilitation. DESIGN: Cross-sectional study. SETTING: Post-acute rehabilitation facility. PARTICIPANTS: Patients (N = 1764) aged 70 years and older admitted over 3 years. MEASUREMENTS: Sociodemographic, medical, and functional data were collected upon admission. Based on discharge diagnoses, patients were classified as cognitively intact, cognitively impaired with no dementia (CIND), and demented. RESULTS: Dementia and CIND were diagnosed in 425 (24.1%) and 301 (17.1%) patients, respectively. Gradients from cognitively intact to cognitively impaired to demented patients were observed in median length of stay (19, 22, and 25 days, P < .001), and institutionalization rates at discharge (4.2%, 7.6%, and 28.8%, P < .001). Among patients discharged home, similar gradients were observed in utilization of home care (68.2%, 79.7%, and 83.3%, P < .001) and day care (3.1%, 7.1%, and 14.3%, P < .001). After adjustment, compared with cognitively intact patients, only those with dementia still had longer stays (+2.7 days) and increased odds of institutionalization (adjOR 6.1, 95% CI 4.0-9.3, P < .001). Among patients discharged home, use of home and day care remained higher in those with dementia (adjOR 1.8, 95% CI 1.2-2.7, P = .005, and adjOR 1.8, 95% CI 1.2-2.7, P = .005, respectively), while CIND patients had higher odds of using home care (adjOR 1.6, 95% CI 1.1-2.4, P = .028). CONCLUSION: Among patients undergoing post-acute rehabilitation, those with dementia had increased use of both institutional and community care, whereas those with CIND had increased use of home care services only. Future studies should investigate specific strategies susceptible to reduce the related burden on health care systems.

The Digital Memory of Catalonia, Consortium of Academic Libraries of Catalonia

The Digital Memory of Catalonia, Consortium of Academic Libraries of Catalonia, contains open-access digitized collections of photographs, drawings, maps, posters, pamphlets, incunabula, ancient Catalan periodicals and many other items with a total of over two million documents related to Catalonia from 18 different institutions (universities, specialized libraries, institutes, archives, etc.).