Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

The joint R&D project: The case of the first Brazilian microcontroller chip

ABSTRACT The interorganizational cooperation, through joint efforts with various actors, allows the high-tech companies to complement resources, especially in R&D projects. Collaborative projects have been identified in many studies as an important strategy to produce complex products and services in uncertain and competitive environments. Thus, this research aims at deepening the understanding of how the development dynamics of a collaborative R&D project in an industry of high technology occur. In order to achieve the proposed objective, the R&D project of the first microcontroller in the Brazilian semiconductor industry was defined as the object of analysis. The empirical choice is justified by the uniqueness of the case, besides bringing a diversity of actors and a level of complementarity of resources that were significant to the success of the project. Given the motivation to know who the actors were and what the main forms of interorganizational coordination were used in this project, interviews were carried out and a questionnaire was also made, besides other documents related to the project. The results presented show a network of nine actors and their roles in the interorganizational collaboration process, as well as the forms of social and temporal overlapping, used in the coordination of collective efforts. Focusing on the mechanisms of temporal and social integration highlighted throughout the study, the inclusion of R&D projects in the typology for interorganizational projects is proposed in this paper, which was also proposed by Jones and Lichtenstein (2008).

Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir.

BACKGROUND: Antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) and didanosine (ddI) has been associated with poor immune recovery despite virologic success. This effect might be related to ddI toxicity since ddI exposure is substantially increased by TDF. OBJECTIVE: To analyze whether immune recovery during ART with TDF and ddI is ddI-dose dependent. DESIGN AND METHODS: A retrospective longitudinal analysis of immune recovery measured by the CD4 T-cell slope in 614 patients treated with ART containing TDF with or without ddI. Patients were stratified according to the tertiles of their weight-adjusted ddI dose: low dose (< 3.3 mg/kg), intermediate dose (3.3-4.1 mg/kg) and high dose (> 4.1 mg/kg). Cofactors modifying the degree of immune recovery after starting TDF-containing ART were identified by univariable and multivariable linear regression analyses. RESULTS: CD4 T-cell slopes were comparable between patients treated with TDF and a weight-adjusted ddI-dose of < 4.1 mg/kg per day (n = 143) versus TDF-without-ddI (n = 393). In the multivariable model the slopes differed by -13 CD4 T cells/mul per year [95% confidence interval (CI), -42 to 17; P = 0.40]. In contrast, patients treated with TDF and a higher ddI dose (> 4.1 mg/kg per day, n = 78) experienced a significantly impaired immune recovery (-47 CD4 T cells/microl per year; 95% CI, -82 to -12; P = 0.009). The virologic response was comparable between the different treatment groups. CONCLUSIONS: Immune recovery is impaired, when high doses of ddI (> 4.1 mg/kg) are given in combination with TDF. If the dose of ddI is adjusted to less than 4.1 mg/kg per day, immune recovery is similar to other TDF-containing ART regimen.

Tree-based message diffusion for managing replicated data in unreliable and resource-constrained peer-to-peer environment

Abstract This thesis proposes a set of adaptive broadcast solutions and an adaptive data replication solution to support the deployment of P2P applications. P2P applications are an emerging type of distributed applications that are running on top of P2P networks. Typical P2P applications are video streaming, file sharing, etc. While interesting because they are fully distributed, P2P applications suffer from several deployment problems, due to the nature of the environment on which they perform. Indeed, defining an application on top of a P2P network often means defining an application where peers contribute resources in exchange for their ability to use the P2P application. For example, in P2P file sharing application, while the user is downloading some file, the P2P application is in parallel serving that file to other users. Such peers could have limited hardware resources, e.g., CPU, bandwidth and memory or the end-user could decide to limit the resources it dedicates to the P2P application a priori. In addition, a P2P network is typically emerged into an unreliable environment, where communication links and processes are subject to message losses and crashes, respectively. To support P2P applications, this thesis proposes a set of services that address some underlying constraints related to the nature of P2P networks. The proposed services include a set of adaptive broadcast solutions and an adaptive data replication solution that can be used as the basis of several P2P applications. Our data replication solution permits to increase availability and to reduce the communication overhead. The broadcast solutions aim, at providing a communication substrate encapsulating one of the key communication paradigms used by P2P applications: broadcast. Our broadcast solutions typically aim at offering reliability and scalability to some upper layer, be it an end-to-end P2P application or another system-level layer, such as a data replication layer. Our contributions are organized in a protocol stack made of three layers. In each layer, we propose a set of adaptive protocols that address specific constraints imposed by the environment. Each protocol is evaluated through a set of simulations. The adaptiveness aspect of our solutions relies on the fact that they take into account the constraints of the underlying system in a proactive manner. To model these constraints, we define an environment approximation algorithm allowing us to obtain an approximated view about the system or part of it. This approximated view includes the topology and the components reliability expressed in probabilistic terms. To adapt to the underlying system constraints, the proposed broadcast solutions route messages through tree overlays permitting to maximize the broadcast reliability. Here, the broadcast reliability is expressed as a function of the selected paths reliability and of the use of available resources. These resources are modeled in terms of quotas of messages translating the receiving and sending capacities at each node. To allow a deployment in a large-scale system, we take into account the available memory at processes by limiting the view they have to maintain about the system. Using this partial view, we propose three scalable broadcast algorithms, which are based on a propagation overlay that tends to the global tree overlay and adapts to some constraints of the underlying system. At a higher level, this thesis also proposes a data replication solution that is adaptive both in terms of replica placement and in terms of request routing. At the routing level, this solution takes the unreliability of the environment into account, in order to maximize reliable delivery of requests. At the replica placement level, the dynamically changing origin and frequency of read/write requests are analyzed, in order to define a set of replica that minimizes communication cost.

Size-dependent predation by Dugesia lugubris (Turbellaria) on Physa acuta (Gastropoda): experiments and model

1. We investigated experimentally predation by the flatworm Dugesia lugubris on the snail Physa acuta in relation to predator body length and to prey morphology [shell length (SL) and aperture width (AW)]. 2. SL and AW correlate strongly in the field, but display significant and independent variance among populations. In the laboratory, predation by Dugesia resulted in large and significant selection differentials on both SL and AW. Analysis of partial effects suggests that selection on AW was indirect, and mediated through its strong correlation with SL. 3. The probability P(ij) for a snail of size category i (SL) to be preyed upon by a flatworm of size category j was fitted with a Poisson-probability distribution, the mean of which increased linearly with predator size (i). Despite the low number of parameters, the fit was excellent (r2 = 0.96). We offer brief biological interpretations of this relationship with reference to optimal foraging theory. 4. The largest size class of Dugesia (>2 cm) did not prey on snails larger than 7 mm shell length. This size threshold might offer Physa a refuge against flatworm predation and thereby allow coexistence in the field. 5. Our results are further discussed with respect to previous field and laboratory observations on P acuta life-history patterns, in particular its phenotypic variance in adult body size.

Free-and open source software for a course on network management: authoring and enactment of scripts based on collaborative learning strategies

This paper describes a Computer-Supported Collaborative Learning (CSCL) case study in engineering education carried out within the context of a network management course. The case study shows that the use of two computing tools developed by the authors and based on Free- and Open-Source Software (FOSS) provide significant educational benefits over traditional engineering pedagogical approaches in terms of both concepts and engineering competencies acquisition. First, the Collage authoring tool guides and supports the course teacher in the process of authoring computer-interpretable representations (using the IMS Learning Design standard notation) of effective collaborative pedagogical designs. Besides, the Gridcole system supports the enactment of that design by guiding the students throughout the prescribed sequence of learning activities. The paper introduces the goals and context of the case study, elaborates onhow Collage and Gridcole were employed, describes the applied evaluation methodology, anddiscusses the most significant findings derived from the case study.

Is spinal stenosis assessment dependent on slice orientation? A magnetic resonance imaging study.

INTRODUCTION: Lumbar spinal stenosis (LSS) treatment is based primarily on the clinical criteria providing that imaging confirms radiological stenosis. The radiological measurement more commonly used is the dural sac cross-sectional area (DSCA). It has been recently shown that grading stenosis based on the morphology of the dural sac as seen on axial T2 MRI images, better reflects severity of stenosis than DSCA and is of prognostic value. This radiological prospective study investigates the variability of surface measurements and morphological grading of stenosis for varying degrees of angulation of the T2 axial images relative to the disc space as observed in clinical practice. MATERIALS AND METHODS: Lumbar spine TSE T2 three-dimensional (3D) MRI sequences were obtained from 32 consecutive patients presenting with either suspected spinal stenosis or low back pain. Axial reconstructions using the OsiriX software at 0°, 10°, 20° and 30° relative to the disc space orientation were obtained for a total of 97 levels. For each level, DSCA was digitally measured and stenosis was graded according to the 4-point (A-D) morphological grading by two observers. RESULTS: A good interobserver agreement was found in grade evaluation of stenosis (k = 0.71). DSCA varied significantly as the slice orientation increased from 0° to +10°, +20° and +30° at each level examined (P < 0.0001) (-15 to +32% at 10°, -24 to +143% at 20° and -29 to +231% at 30° of slice orientation). Stenosis definition based on the surface measurements changed in 39 out of the 97 levels studied, whereas the morphology grade was modified only in two levels (P < 0.01). DISCUSSION: The need to obtain continuous slices using the classical 2D MRI acquisition technique entails often at least a 10° slice inclination relative to one of the studied discs. Even at this low angulation, we found a significantly statistical difference between surface changes and morphological grading change. In clinical practice, given the above findings, it might therefore not be necessary to align the axial cuts to each individual disc level which could be more time-consuming than obtaining a single series of axial cuts perpendicular to the middle of the lumbar spine or to the most stenotic level. In conclusion, morphological grading seems to offer an alternative means of assessing severity of spinal stenosis that is little affected by image acquisition technique.

Time-resolved lanthanide luminescence for lab-on-a-chip detection of biomarkers on cancerous tissues.

PDMS-based microfluidic devices combined with lanthanide-based immunocomplexes have been successfully tested for the multiplex detection of biomarkers on cancerous tissues, revealing an enhanced sensitivity compared to classical organic dyes.

Social network of family caregivers of disabled and dependent patients

Cross-sectional study that used the Social Network Index and the genogram to assess the social network of 110 family caregivers of dependent patients attended by a Home Care Service in São Paulo, Brazil. Data were analyzed using the test U of Mann-Whitney, Kruskal-Wallis and Spearman correlation. Results were considered statistically significant when p<0,05. Few caregivers participated in activities outside the home and the average number of people they had a bond was 4,4 relatives and 3,6 friends. Caregivers who reported pain and those who had a partner had higher average number of relatives who to trust. The average number of friends was higher in the group that reported use of medication for depression. Total and per capita incomes correlated with the social network. It was found that family members are the primary caregiver’s social network.





Effects of thyromimetic drugs on aldosterone-dependent sodium transport in the toad bladder.

Aldosterone increases transepithelial Na+ transport in the urinary bladder of Bufo marinus. The response is characterized by 3 distinct phases: 1) a lag period of about 60 min, ii) an initial phase (early response) of about 2 hr during which Na+ transport increases rapidly and transepithelial electrical resistance falls, and iii) a late phase (late response) of about 4 to 6 hr during which Na+ transport still increases significantly but with very little change in resistance. Triiodothyronine (T3, 6 nM) added either 2 or 18 hr before aldosterone selectively antagonizes the late response. T3 per se (up to 6 nM) has no effect on base-line Na+ transport. The antagonist activity of T3 is only apparent after a latent period of about 6 to 8 hr. It is not rapidly reversible after a 4-hr washout of the hormone. The effects appear to be selective for thyromimetic drugs since reverse T3 (rT3) is inactive and isopropyldiiodothyronine (isoT2) is more active than T3. The relative activity of these analogs corresponds to their relative affinity for T3 nuclear binding sites which we have previously described. Our data suggest that T3 might control the expression of aldosterone by regulating gene expression, e.g. by the induction of specific proteins, which in turn will inhibit the late mineralocorticoid response, without interaction with the early response.

Inverse association between circulating vitamin D and mortality-dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures.

An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to study the maturation-dependent sensitivity of brain cells to two organophosphorus pesticides (OPs), chlorpyrifos and parathion, and to their oxon derivatives. Immature (DIV 5-15) or differentiated (DIV 25-35) brain cells were treated continuously for 10 days. Acetylcholinesterase (AChE) inhibitory potency for the OPs was compared to that of eserine (physostigmine), a reversible AChE inhibitor. Oxon derivatives were more potent AChE inhibitors than the parent compounds, and parathion was more potent than chlorpyrifos. No maturation-dependent differences for AChE inhibition were found for chlorpyrifos and eserine, whereas for parathion and paraoxon there was a tendency to be more effective in immature cultures, while the opposite was true for chlorpyrifos-oxon. Toxic effects, assessed by measuring protein content as an index of general cytotoxicity, and various enzyme activities as cell-type-specific neuronal and glial markers (ChAT and GAD, for cholinergic and GABAergic neurons, respectively, and GS and CNP, for astrocytes and oligodendrocytes, respectively) were only found at more than 70% of AChE inhibition. Immature compared to differentiated cholinergic neurons appeared to be more sensitive to OP treatments. The oxon derivates were found to be more toxic on neurons than the parent compounds, and chlorpyrifos was more toxic than parathion. Eserine was not neurotoxic. These results indicate that inhibition of AChE remains the most sensitive macromolecular target of OP exposure, since toxic effects were found at concentrations in which AChE was inhibited. Furthermore, the compound-specific reactions, the differential pattern of toxicity of OPs compared to eserine, and the higher sensitivity of immature brain cells suggest that the toxic effects and inhibition of AChE are unrelated.

Reduction of Helicobacter infection in IL-10-/- mice is dependent on CD4+ T cells but not on mast cells.

BACKGROUND: In contrast to wild type, interleukin-10-deficient (IL-10(-/-)) mice are able to clear Helicobacter infection. In this study, we investigated the immune response of IL-10(-/-) mice leading to the reduction of Helicobacter infection. MATERIALS AND METHODS: We characterized the immune responses of Helicobacter felis-infected IL-10(-/-) mice by studying the systemic antibody and cellular responses toward Helicobacter. We investigated the role of CD4(+) T cells in the Helicobacter clearance by injecting H. felis-infected IL-10(-/-) mice with anti-CD4 depleting antibodies. To examine the role of mast cells in Helicobacter clearance, we constructed and infected mast cells and IL-10 double-deficient mice. RESULTS: Reduction of Helicobacter infection in IL-10(-/-) mice is associated with strong humoral (fivefold higher serum antiurease antibody titers were measured in IL-10(-/-) in comparison to wild-type mice, p < .008) and cellular (urease-stimulated splenic CD4(+) T cells isolated from infected IL-10(-/-) mice produce 150-fold more interferon-gamma in comparison to wild-type counterparts, p < .008) immune responses directed toward Helicobacter. Depletion of CD4(+) cells from Helicobacter-infected IL-10(-/-) mice lead to the loss of bacterial clearance (rapid urease tests are threefold higher in CD4(+) depleted IL-10(-/-) in comparison to nondepleted IL-10(-/-) mice, p < .02). Mast cell IL-10(-/-) double-deficient mice clear H. felis infection, indicating that mast cells are unnecessary for the bacterial eradication in IL-10(-/-) mice. CONCLUSION: Taken together, these results suggest that CD4(+) cells are required for Helicobacter clearance in IL-10(-/-) mice. This reduction of Helicobacter infection is, however, not dependent on the mast cell population.