Nouveautés thérapeutiques 2008 en médecine interne hospitalière: perspective des chefs de clinique [Highlights 2008 in a university hospital-based internal medicine: the point of view from the chief residents]

Doctors must regularly adjust their patients' care according to recent relevant publications. The chief residents from the Department of Internal Medicine of a university hospital present some major themes of internal medicine treated during the year 2008, such as heart failure, diabetes, COPD, and thromboembolic disease. Emphasis will be placed primarily on changes in the daily hospital practice induced by these recent studies. This variety of topics illustrates both the broad spectrum of the current internal medicine, and the many uncertainties associated with modem medical practice based on evidence.

Risk factors associated with human papillomavirus infection in two populations from Rio de Janeiro, Brazil

We investigated human papillomavirus (HPV) infection in two female populations from diverse socio-economic strata from the state of Rio de Janeiro and we also investigated the possible co-factors related to infection and the progression to cancer. In Group I, the reference group of this study, 10.7% of the patients presented HPV infection, as detected by generic PCR, while in Group II (low socio-demographic conditions) HPV was detected in 31.1% of the samples. HPV16 was the most prevalent virus type found in both Groups I and II (5.3% and 10%, respectively), followed by HPV 18 (1.3% and 4.7%, respectively). Although only a small sample was analysed, we detected differences among the groups regarding the rates of HPV infection, HPV types, age, ethnicity, familial income, schooling, marital status, parity, tobacco smoking and oral contraceptive use. For Group I, the Papanicolaou test was the most powerful independent factor associated with HPV status, followed by an age of under 30 years old, the number of sexual partners and black ethnicity. Our data are in agreement with the co-factors that are typically described for the developed world. For Group II, the Pap test was also the most relevant variable that was analysed, but the history of other sexually transmitted diseases and the use of alcohol were additional factors that were implicated in infection. These findings point out the need for the development of general and specific strategies for HPV screening of all Brazilian women.

Remodeling of DNA replication structures by the branch point translocase FANCM

Fanconi anemia (FA) is a genetically heterogeneous chromosome instability syndrome associated with congenital abnormalities, bone marrow failure, and cancer predisposition. Eight FA proteins form a nuclear core complex, which promotes tolerance of DNA lesions in S phase, but the underlying mechanisms are still elusive. We reported recently that the FA core complex protein FANCM can translocate Holliday junctions. Here we show that FANCM promotes reversal of model replication forks via concerted displacement and annealing of the nascent and parental DNA strands. Fork reversal by FANCM also occurs when the lagging strand template is partially single-stranded and bound by RPA. The combined fork reversal and branch migration activities of FANCM lead to extensive regression of model replication forks. These observations provide evidence that FANCM can remodel replication fork structures and suggest a mechanism by which FANCM could promote DNA damage tolerance in S phase

A quality-based cost distribution charging scheme for QoS multicast networks

This paper presents a new charging scheme for cost distribution along a point-to-multipoint connection when destination nodes are responsible for the cost. The scheme focus on QoS considerations and a complete range of choices is presented. These choices go from a safe scheme for the network operator to a fair scheme to the customer. The in-between cases are also covered. Specific and general problems, like the incidence of users disconnecting dynamically is also discussed. The aim of this scheme is to encourage the users to disperse the resource demand instead of having a large number of direct connections to the source of the data, which would result in a higher than necessary bandwidth use from the source. This would benefit the overall performance of the network. The implementation of this task must balance between the necessity to offer a competitive service and the risk of not recovering such service cost for the network operator. Throughout this paper reference to multicast charging is made without making any reference to any specific category of service. The proposed scheme is also evaluated with the criteria set proposed in the European ATM charging project CANCAN

Manufacturing and characterization of a recombinant adeno-associated virus type 8 reference standard material.

Gene therapy approaches using recombinant adeno-associated virus serotype 2 (rAAV2) and serotype 8 (rAAV8) have achieved significant clinical benefits. The generation of rAAV Reference Standard Materials (RSM) is key to providing points of reference for particle titer, vector genome titer, and infectious titer for gene transfer vectors. Following the example of the rAAV2RSM, here we have generated and characterized a novel RSM based on rAAV serotype 8. The rAAV8RSM was produced using transient transfection, and the purification was based on density gradient ultracentrifugation. The rAAV8RSM was distributed for characterization along with standard assay protocols to 16 laboratories worldwide. Mean titers and 95% confidence intervals were determined for capsid particles (mean, 5.50×10(11) pt/ml; CI, 4.26×10(11) to 6.75×10(11) pt/ml), vector genomes (mean, 5.75×10(11) vg/ml; CI, 3.05×10(11) to 1.09×10(12) vg/ml), and infectious units (mean, 1.26×10(9) IU/ml; CI, 6.46×10(8) to 2.51×10(9) IU/ml). Notably, there was a significant degree of variation between institutions for each assay despite the relatively tight correlation of assay results within an institution. This outcome emphasizes the need to use RSMs to calibrate the titers of rAAV vectors in preclinical and clinical studies at a time when the field is maturing rapidly. The rAAV8RSM has been deposited at the American Type Culture Collection (VR-1816) and is available to the scientific community.

On optimal computation of MPLS label binding for multipoint-to-point connections

Most network operators have considered reducing Label Switched Routers (LSR) label spaces (i.e. the number of labels that can be used) as a means of simplifying management of underlaying Virtual Private Networks (VPNs) and, hence, reducing operational expenditure (OPEX). This letter discusses the problem of reducing the label spaces in Multiprotocol Label Switched (MPLS) networks using label merging - better known as MultiPoint-to-Point (MP2P) connections. Because of its origins in IP, MP2P connections have been considered to have tree- shapes with Label Switched Paths (LSP) as branches. Due to this fact, previous works by many authors affirm that the problem of minimizing the label space using MP2P in MPLS - the Merging Problem - cannot be solved optimally with a polynomial algorithm (NP-complete), since it involves a hard- decision problem. However, in this letter, the Merging Problem is analyzed, from the perspective of MPLS, and it is deduced that tree-shapes in MP2P connections are irrelevant. By overriding this tree-shape consideration, it is possible to perform label merging in polynomial time. Based on how MPLS signaling works, this letter proposes an algorithm to compute the minimum number of labels using label merging: the Full Label Merging algorithm. As conclusion, we reclassify the Merging Problem as Polynomial-solvable, instead of NP-complete. In addition, simulation experiments confirm that without the tree-branch selection problem, more labels can be reduced

Decentralized model reference control of flexible cable-stayed beam structures

A decentralized model reference controller is designed to reduce the magnitude of the transversal vibration of a flexible cable-stayed beam structure induced by a seismic excitation. The controller design is made based on the principle of sliding mode such that a priori knowledge

Conceptual framework and pilot study to benchmark phylogenomic databases based on reference gene trees.

Phylogenomic databases provide orthology predictions for species with fully sequenced genomes. Although the goal seems well-defined, the content of these databases differs greatly. Seven ortholog databases (Ensembl Compara, eggNOG, HOGENOM, InParanoid, OMA, OrthoDB, Panther) were compared on the basis of reference trees. For three well-conserved protein families, we observed a generally high specificity of orthology assignments for these databases. We show that differences in the completeness of predicted gene relationships and in the phylogenetic information are, for the great majority, not due to the methods used, but to differences in the underlying database concepts. According to our metrics, none of the databases provides a fully correct and comprehensive protein classification. Our results provide a framework for meaningful and systematic comparisons of phylogenomic databases. In the future, a sustainable set of 'Gold standard' phylogenetic trees could provide a robust method for phylogenomic databases to assess their current quality status, measure changes following new database releases and diagnose improvements subsequent to an upgrade of the analysis procedure.

Laboratory detection of respiratory viruses by automated techniques.

Advances in clinical virology for detecting respiratory viruses have been focused on nucleic acids amplification techniques, which have converted in the reference method for the diagnosis of acute respiratory infections of viral aetiology. Improvements of current commercial molecular assays to reduce hands-on-time rely on two strategies, a stepwise automation (semi-automation) and the complete automation of the whole procedure. Contributions to the former strategy have been the use of automated nucleic acids extractors, multiplex PCR, real-time PCR and/or DNA arrays for detection of amplicons. Commercial fully-automated molecular systems are now available for the detection of respiratory viruses. Some of them could convert in point-of-care methods substituting antigen tests for detection of respiratory syncytial virus and influenza A and B viruses. This article describes laboratory methods for detection of respiratory viruses. A cost-effective and rational diagnostic algorithm is proposed, considering technical aspects of the available assays, infrastructure possibilities of each laboratory and clinic-epidemiologic factors of the infection.

Identification of reference genes for quantitative RT-PCR in ascending aortic aneurysms.

Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue.

Els marges del pensament polític contemporani

La crisi i esfondrament del pensament metafísic heretat de la modernitat deixa la filosofia contemporània davant d'un nou paradigma on el coneixement s’ha de construir prescindint de tota identitat i fonamentació. El meu projecte s’estableix com un recorregut descendent que parteix d’un àmbit concret, com és el del problema de la manca de fonamentació en la filosofia política contemporània, per arribar a la veritable arrel del problema general que no és altre que la mateixa naturalesa del llenguatge filosòfic. El punt de partida és la pregunta sobre la possibilitat d’una filosofia política en termes postmetafísics. La filosofia política, atrapada entre les forces de la tirania unitària del concepte metafísic i la dissolució pràctica en pro de la realitat instrumental, traça ponts cap a l’estètica i la deconstrucció, que tenen com a corol•lari final qüestionar-nos els propis límits del pensament polític. El concepte d’impolític és una sortida deconstructiva a aquest atzucac. Des d’Esposito, Rancière, Nancy, però sobretot Massimo Cacciari, he aprofundit en el paradigma postmetafísic que origina aquesta negació política de la pròpia política, política com els seus límits, relació com a distància i identitat com a silenci. És evident que la clau de volta és l’herència i recepció contemporània de Nietzsche i la seva crítica a la transcendentalitat moderna en el sí de l’elaboració d’un coneixement en un naufragi constant pel fracàs de la síntesi que anhela. És aquesta herència la que ha possibilitat aquest pensament negatiu contemporani, el del joc wittgensteinià, la deconstrucció del valor que queda convertit en el seu propi marge (Derrida). Definim així no només una comunitat política basada en la incommensurabilitat dels seus membres alhora buits de contingut (Musil), sinó un model de llenguatge que és el seu propi silenci, un llenguatge en contínua lluita contra sí mateix. El meu projecte és una relectura d’aquesta veritat no identitària on el concepte de diàleg pren una importància cabdal. La filosofia de la música aquí es presenta com un terreny fèrtil d’eines conceptuals a l’hora de desenvolupar-ho. La música és el llenguatge negatiu que només troba possibilitat en la seva pròpia impossibilitat de contingut sintètic. Més enllà de les referències obligatòries a chönberg i Adorno entre altres, el camí iniciat per Bergson amb la introducció de la temporalitat a la discussió obra la porta al paper de l’esdveniment en aquest discurs sobre la impossibilitat. Tornant a la filosofia, on el propi llenguatge filosòfic es defineix ja com a impossible, l’esdeveniment reobre l’antiga tensió entre l’escriptura i la paraula viva, veritable fonament del problema, i vèrtex de la possibilitat d’aquesta filosofia impossible.