In vitro activity of fosfomycin against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: comparison of susceptibility testing procedures

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.

Postmortem circulation: a new model for testing endovascular devices and training clinicians in their use.

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients.

Testing of Diagnostic Methods for Detection of Influenza Virusfor Optimal Performance in the Context of an Influenza Surveillance Network

Influenza surveillance networks must detect early the viruses that will cause the forthcoming annual epidemics and isolate the strains for further characterization. We obtained the highest sensitivity (95.4%) with a diagnostic tool that combined a shell-vial assay and reverse transcription-PCR on cell culture supernatants at 48 h, and indeed, recovered the strain

The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.

Compositional hypotheses of subcompositional stability and specific perturbation change and their testing

In standard multivariate statistical analysis common hypotheses of interest concern changes in mean vectors and subvectors. In compositional data analysis it is now well established that compositional change is most readily described in terms of the simplicial operation of perturbation and that subcompositions replace the marginal concept of subvectors. To motivate the statistical developments of this paper we present two challenging compositional problems from food production processes.Against this background the relevance of perturbations and subcompositions can beclearly seen. Moreover we can identify a number of hypotheses of interest involvingthe specification of particular perturbations or differences between perturbations and also hypotheses of subcompositional stability. We identify the two problems as being the counterpart of the analysis of paired comparison or split plot experiments and of separate sample comparative experiments in the jargon of standard multivariate analysis. We then develop appropriate estimation and testing procedures for a complete lattice of relevant compositional hypotheses

Methods for testing association between uncertain genotypes and quantitative traits.

Interpretability and power of genome-wide association studies can be increased by imputing unobserved genotypes, using a reference panel of individuals genotyped at higher marker density. For many markers, genotypes cannot be imputed with complete certainty, and the uncertainty needs to be taken into account when testing for association with a given phenotype. In this paper, we compare currently available methods for testing association between uncertain genotypes and quantitative traits. We show that some previously described methods offer poor control of the false-positive rate (FPR), and that satisfactory performance of these methods is obtained only by using ad hoc filtering rules or by using a harsh transformation of the trait under study. We propose new methods that are based on exact maximum likelihood estimation and use a mixture model to accommodate nonnormal trait distributions when necessary. The new methods adequately control the FPR and also have equal or better power compared to all previously described methods. We provide a fast software implementation of all the methods studied here; our new method requires computation time of less than one computer-day for a typical genome-wide scan, with 2.5 M single nucleotide polymorphisms and 5000 individuals.

Testing the validity of a set of diagnostic criteria for sensory neuronopathies: a francophone collaborative study.

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria on a French multicenter study. 210 patients with sensory neuropathies from 15 francophone reference centers for neuromuscular diseases were included in the study with an expert diagnosis of non-SNN, SNN or suspected SNN according to the investigations performed in these centers. Diagnosis was obtained independently from the set of criteria to be tested. The expert diagnosis was taken as the reference against which the proposed SNN criteria were tested. The set relied on clinical and electrophysiological data easily obtainable with routine investigations. 9/61 (16.4 %) of non-SNN patients, 23/36 (63.9 %) of suspected SNN, and 102/113 (90.3 %) of SNN patients according to the expert diagnosis were classified as SNN by the criteria. The SNN criteria tested against the expert diagnosis in the SNN and non-SNN groups had 90.3 % (102/113) sensitivity, 85.2 % (52/61) specificity, 91.9 % (102/111) positive predictive value, and 82.5 % (52/63) negative predictive value. Discordance between the expert diagnosis and the SNN criteria occurred in 20 cases. After analysis of these cases, 11 could be reallocated to a correct diagnosis in accordance with the SNN criteria. The proposed criteria may be useful for the diagnosis of probable SNN in patients with sensory neuropathy. They can be reached with simple clinical and paraclinical investigations.

WMR navigation using local potential field corridors and narrow local occupancy grid perception

Path planning and control strategies applied to autonomous mobile robots should fulfil safety rules as well as achieve final goals. Trajectory planning applications should be fast and flexible to allow real time implementations as well as environment interactions. The methodology presented uses the on robot information as the meaningful data necessary to plan a narrow passage by using a corridor based on attraction potential fields that approaches the mobile robot to the final desired configuration. It employs local and dense occupancy grid perception to avoid collisions. The key goals of this research project are computational simplicity as well as the possibility of integrating this method with other methods reported by the research community. Another important aspect of this work consist in testing the proposed method by using a mobile robot with a perception system composed of a monocular camera and odometers placed on the two wheels of the differential driven motion system. Hence, visual data are used as a local horizon of perception in which trajectories without collisions are computed by satisfying final goal approaches and safety criteria

Partial disjoint path for multi-layer protection in GMPLS networks

In this paper, different recovery methods applied at different network layers and time scales are used in order to enhance the network reliability. Each layer deploys its own fault management methods. However, current recovery methods are applied to only a specific layer. New protection schemes, based on the proposed partial disjoint path algorithm, are defined in order to avoid protection duplications in a multi-layer scenario. The new protection schemes also encompass shared segment backup computation and shared risk link group identification. A complete set of experiments proves the efficiency of the proposed methods in relation with previous ones, in terms of resources used to protect the network, the failure recovery time and the request rejection ratio

The long and painful path towards arthroplasty: A qualitative study

Hip or knee arthroplasty is proposed after osteoarthritis or an accident. It is decided after a long path of pain and decrease in the quality of life. This research explores the period of illness until surgery. Twenty-four semi-structured interviews were conducted one month before surgery and a thematic discourse analysis performed. The diversity and complexity of the patient experience, in a commonly performed surgical intervention underlines important topics, requiring attention in order to improve patient preparations and information prior to arthroplasty: information adapted to individual concerns, needs and representations. Psychological and physical acceptance is necessary for integration of the prosthesis.

Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects.

Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric disorders, i.e., anxiety disorders, depression, and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB) system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R) in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD), the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation.

Clinical data and molecular analysis of Mycobacterium tuberculosis isolates from drug-resistant tuberculosis patients in Goiás, Brazil

Drug resistance is one of the major concerns regarding tuberculosis (TB) infection worldwide because it hampers control of the disease. Understanding the underlying mechanisms responsible for drug resistance development is of the highest importance. To investigate clinical data from drug-resistant TB patients at the Tropical Diseases Hospital, Goiás (GO), Brazil and to evaluate the molecular basis of rifampin (R) and isoniazid (H) resistance in Mycobacterium tuberculosis. Drug susceptibility testing was performed on 124 isolates from 100 patients and 24 isolates displayed resistance to R and/or H. Molecular analysis of drug resistance was performed by partial sequencing of the rpoB and katGgenes and analysis of the inhA promoter region. Similarity analysis of isolates was performed by 15 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. The molecular basis of drug resistance among the 24 isolates from 16 patients was confirmed in 18 isolates. Different susceptibility profiles among the isolates from the same individual were observed in five patients; using MIRU-VNTR, we have shown that those isolates were not genetically identical, with differences in one to three loci within the 15 analysed loci. Drug-resistant TB in GO is caused by M. tuberculosis strains with mutations in previously described sites of known genes and some patients harbour a mixed phenotype infection as a consequence of a single infective event; however, further and broader investigations are needed to support our findings.

Mosaico mediterráneo. El Arte como herramienta de diálogo intercultural

El presente trabajo de investigación doctoral reflexiona sobre el aporte de las prácticas artísticas contemporáneas en los procesos de diálogo entre culturas en el Mediterráneo. En las dinámicas de percepción, acercamiento y (re)conocimiento del otro y de las culturas otras, todos los medios informativos y de comunicación pueden ser, por un lado, válidos y efectivos como, por otro, pueden desviar de la verdad y difundir fácilmente numerosos prejuicios. Frente a la “síntesis” operada por los medios de comunicación tradicionales, donde “el Otro” es a menudo objeto de representaciones estereotipadas, las prácticas artísticas, en su sentido más amplio, contraponen un “análisis” que puede permitir, en diferentes casos, la eliminación de las barreras y un mayor acercamiento a la cultura otra. En la presente investigación se quiere trazar un itinerario teórico que parte de las hipótesis orientalistas, pasa por las filosofías del encuentro con el otro; los estudios sobre la participación; las actuales reflexiones sobre la estética relacional; las definiciones históricas y socio-políticas del Mediterráneo; hasta llegar a reconocer en el arte, en la creación artística, el medio de comunicación más eficaz y penetrante a la hora de refinar el conocimiento y (re)descubrir los diferentes aspectos de las culturas de los países y de los pueblos del Mediterráneo. En el espacio plural del Mediterráneo las prácticas artísticas y creativas actuales actúan como un campo de experimentación y un territorio de debate valioso e importante para el desarrollo del discurso intercultural.

Application of Molecular Diagnostic Techniques for Viral Testing.

Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses. These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis. The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide. This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory. Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases. The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care. The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care. The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory.