In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung: a dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing11Workshop on 'In-Vitro Exposure Studies for Toxicity Testing of Engineered Nanoparticles' sponsored by the Association for Aerosol Research (GAeF), 5-6 September 2009, Karlsruhe, Germany. an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5mg/m3 (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10-5-5×10-3μg/h/cm2 of lung tissue and 2-300particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

Hilbert space on probability density functions with Aitchison geometry

Compositional data analysis motivated the introduction of a complete Euclidean structure in the simplex of D parts. This was based on the early work of J. Aitchison (1986) and completed recently when Aitchinson distance in the simplex was associated with an inner product and orthonormal bases were identified (Aitchison and others, 2002; Egozcue and others, 2003). A partition of the support of a random variable generates a composition by assigning the probability of each interval to a part of the composition. One can imagine that the partition can be refined and the probability density would represent a kind of continuous composition of probabilities in a simplex of infinitely many parts. This intuitive idea would lead to a Hilbert-space of probability densitiesby generalizing the Aitchison geometry for compositions in the simplex into the set probability densities

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

One major goal of research on Chagas disease is the development of effective chemotherapy to eliminate the infection from individuals who have not yet developed cardiac and/or digestive disease manifestations. Cure evaluation is the more complex aspect of its treatment, often leading to diverse and controversial results. The absence of reliable methods or a diagnostic gold standard to assess etiologic treatment efficacy still constitutes a major challenge. In an effort to develop more sensitive tools, polymerase chain reaction (PCR)-based assays were introduced to detect low amounts of Trypanosoma cruzi DNA in blood samples from chagasic patients, thus improving the diagnosis and follow-up evaluation after chemotherapy. In this article, I review the main problems concerning drug efficacy and criteria used for cure estimation in treated chagasic patients, and the work conducted by different groups on developing PCR methodologies to monitor treatment outcome of congenital infections as well as recent and late chronic T. cruzi infections.

Analyzing shapes as compositions of distances

We propose to analyze shapes as “compositions” of distances in Aitchison geometry asan alternate and complementary tool to classical shape analysis, especially when sizeis non-informative.Shapes are typically described by the location of user-chosen landmarks. Howeverthe shape – considered as invariant under scaling, translation, mirroring and rotation– does not uniquely define the location of landmarks. A simple approach is to usedistances of landmarks instead of the locations of landmarks them self. Distances arepositive numbers defined up to joint scaling, a mathematical structure quite similar tocompositions. The shape fixes only ratios of distances. Perturbations correspond torelative changes of the size of subshapes and of aspect ratios. The power transformincreases the expression of the shape by increasing distance ratios. In analogy to thesubcompositional consistency, results should not depend too much on the choice ofdistances, because different subsets of the pairwise distances of landmarks uniquelydefine the shape.Various compositional analysis tools can be applied to sets of distances directly or afterminor modifications concerning the singularity of the covariance matrix and yield resultswith direct interpretations in terms of shape changes. The remaining problem isthat not all sets of distances correspond to a valid shape. Nevertheless interpolated orpredicted shapes can be backtransformated by multidimensional scaling (when all pairwisedistances are used) or free geodetic adjustment (when sufficiently many distancesare used)

A Bayesian network approach to the database serch problem in criminal proceedings

Background The 'database search problem', that is, the strengthening of a case - in terms of probative value - against an individual who is found as a result of a database search, has been approached during the last two decades with substantial mathematical analyses, accompanied by lively debate and centrally opposing conclusions. This represents a challenging obstacle in teaching but also hinders a balanced and coherent discussion of the topic within the wider scientific and legal community. This paper revisits and tracks the associated mathematical analyses in terms of Bayesian networks. Their derivation and discussion for capturing probabilistic arguments that explain the database search problem are outlined in detail. The resulting Bayesian networks offer a distinct view on the main debated issues, along with further clarity. Methods As a general framework for representing and analyzing formal arguments in probabilistic reasoning about uncertain target propositions (that is, whether or not a given individual is the source of a crime stain), this paper relies on graphical probability models, in particular, Bayesian networks. This graphical probability modeling approach is used to capture, within a single model, a series of key variables, such as the number of individuals in a database, the size of the population of potential crime stain sources, and the rarity of the corresponding analytical characteristics in a relevant population. Results This paper demonstrates the feasibility of deriving Bayesian network structures for analyzing, representing, and tracking the database search problem. The output of the proposed models can be shown to agree with existing but exclusively formulaic approaches. Conclusions The proposed Bayesian networks allow one to capture and analyze the currently most well-supported but reputedly counter-intuitive and difficult solution to the database search problem in a way that goes beyond the traditional, purely formulaic expressions. The method's graphical environment, along with its computational and probabilistic architectures, represents a rich package that offers analysts and discussants with additional modes of interaction, concise representation, and coherent communication.

Improving Clustering Algorithms for Image Segmentation using Contour and Region Information

In image segmentation, clustering algorithms are very popular because they are intuitive and, some of them, easy to implement. For instance, the k-means is one of the most used in the literature, and many authors successfully compare their new proposal with the results achieved by the k-means. However, it is well known that clustering image segmentation has many problems. For instance, the number of regions of the image has to be known a priori, as well as different initial seed placement (initial clusters) could produce different segmentation results. Most of these algorithms could be slightly improved by considering the coordinates of the image as features in the clustering process (to take spatial region information into account). In this paper we propose a significant improvement of clustering algorithms for image segmentation. The method is qualitatively and quantitative evaluated over a set of synthetic and real images, and compared with classical clustering approaches. Results demonstrate the validity of this new approach

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

An improved method for discovering link criticality in transport networks

Quantitatively assessing the importance or criticality of each link in a network is of practical value to operators, as that can help them to increase the network's resilience, provide more efficient services, or improve some other aspect of the service. Betweenness is a graph-theoretical measure of centrality that can be applied to communication networks to evaluate link importance. However, as we illustrate in this paper, the basic definition of betweenness centrality produces inaccurate estimations as it does not take into account some aspects relevant to networking, such as the heterogeneity in link capacity or the difference between node-pairs in their contribution to the total traffic. A new algorithm for discovering link centrality in transport networks is proposed in this paper. It requires only static or semi-static network and topology attributes, and yet produces estimations of good accuracy, as verified through extensive simulations. Its potential value is demonstrated by an example application. In the example, the simple shortest-path routing algorithm is improved in such a way that it outperforms other more advanced algorithms in terms of blocking ratio

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Current applications of cardiac magnetic resonance (CMR) imaging offer a wide spectrum of indications in the setting of acute cardiac care. In particular, CMR is helpful for the differential diagnosis of chest pain by detection of myocarditis and pericarditis. Also, takotsubo cardiomyopathy and acute aortic diseases can be evaluated by CMR and are important differential diagnoses in patients with acute chest pain. In patients with restricted windows for echocardiography, CMR is the method of choice to evaluate complications of acute myocardial infarction (AMI). In AMI, CMR allows for a unique characterization of myocardial damage by quantifying necrosis, microvascular obstruction, oedema (=area at risk), and haemorrhage. These capabilities will help us to understand better the pathophysiological events during infarction and will also allow to assess new treatment strategies in AMI. To what extent the information on tissue damage will guide patient management is not yet clear and further research in this field is warranted. In the near future, CMR will certainly become more routine in acute cardiac care units, as manufacturers are now focusing strongly on this aspect of user-friendliness. Finally, in the next decade or so, MRI of other nuclei such as fluorine and carbon might become a clinical reality, which would allow for metabolic and targeted molecular imaging with excellent sensitivity and specificity

Assessing the link between coping patterns and interpersonal behaviors in depressed women

Aim. Stressful life events are an important contributor to the onset and course of depression. Coping strategies and interpersonal patterns have been found to mediate the effects of stress [1]. Methods. This study examined the relationship between coping patterns and interpersonal interactions in early psychotherapy sessions of 25 female patients with major depression. Transcripts were rated for coping patterns using the Coping Patterns Rating Scale (CPRS; [2]). Interpersonal patterns were assessed using the Structural Analysis of Social Behavior (SASB; [3]). Results. Significant correlations were found between coping patterns and markers of interpersonal functioning in selected contexts. Discussion. The implications of these findings in understanding an important aspect of vulnerability to depression and enhancing treatment outcome are discussed.

Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses.

The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.

Estimation of the lateral correlation structure of subsurface water content from surface-based ground-penetrating radar reflection images

Over the past decade, significant interest has been expressed in relating the spatial statistics of surface-based reflection ground-penetrating radar (GPR) data to those of the imaged subsurface volume. A primary motivation for this work is that changes in the radar wave velocity, which largely control the character of the observed data, are expected to be related to corresponding changes in subsurface water content. Although previous work has indeed indicated that the spatial statistics of GPR images are linked to those of the water content distribution of the probed region, a viable method for quantitatively analyzing the GPR data and solving the corresponding inverse problem has not yet been presented. Here we address this issue by first deriving a relationship between the 2-D autocorrelation of a water content distribution and that of the corresponding GPR reflection image. We then show how a Bayesian inversion strategy based on Markov chain Monte Carlo sampling can be used to estimate the posterior distribution of subsurface correlation model parameters that are consistent with the GPR data. Our results indicate that if the underlying assumptions are valid and we possess adequate prior knowledge regarding the water content distribution, in particular its vertical variability, this methodology allows not only for the reliable recovery of lateral correlation model parameters but also for estimates of parameter uncertainties. In the case where prior knowledge regarding the vertical variability of water content is not available, the results show that the methodology still reliably recovers the aspect ratio of the heterogeneity.

Continuidad De Cuidados y Comunicación interniveles entre equipos de emergencias sanitarias y Atención Primaria.

The gradual incorporation of the nurses to the extrahospital emergency teams give them a holistic aspect in the field of care. And this is not possible without addressing the possibility of continuity of care and communication with other levels of care. All efforts in this regard and made speeches themselves as nursing, "Refer" (Nic 8100) and "Exchange of information on health care" (Nic 7960), is the conceptual framework of this work, which objetives are to quantify and exposing the proceedings in this line taken by the nurses of emergency team.

Digital beamforming and moving target indication for future spaceborne synthetic aperture radar

During the last decade the interest on space-borne Synthetic Aperture Radars (SAR) for remote sensing applications has grown as testified by the number of recent and forthcoming missions as TerraSAR-X, RADARSAT-2, COSMO-kyMed, TanDEM-X and the Spanish SEOSAR/PAZ. In this sense, this thesis proposes to study and analyze the performance of the state-of-the-Art space-borne SAR systems, with modes able to provide Moving Target Indication capabilities (MTI), i.e. moving object detection and estimation. The research will focus on the MTI processing techniques as well as the architecture and/ or configuration of the SAR instrument, setting the limitations of the current systems with MTI capabilities, and proposing efficient solutions for the future missions. Two European projects, to which the Universitat Politècnica de Catalunya provides support, are an excellent framework for the research activities suggested in this thesis. NEWA project proposes a potential European space-borne radar system with MTI capabilities in order to fulfill the upcoming European security policies. This thesis will critically review the state-of-the-Art MTI processing techniques as well as the readiness and maturity level of the developed capabilities. For each one of the techniques a performance analysis will be carried out based on the available technologies, deriving a roadmap and identifying the different technological gaps. In line with this study a simulator tool will be developed in order to validate and evaluate different MTI techniques in the basis of a flexible space-borne radar configuration. The calibration of a SAR system is mandatory for the accurate formation of the SAR images and turns to be critical in the advanced operation modes as MTI. In this sense, the SEOSAR/PAZ project proposes the study and estimation of the radiometric budget. This thesis will also focus on an exhaustive analysis of the radiometric budget considering the current calibration concepts and their possible limitations. In the framework of this project a key point will be the study of the Dual Receive Antenna (DRA) mode, which provides MTI capabilities to the mission. An additional aspect under study is the applicability of the Digital Beamforming on multichannel and/or multistatic radar platforms, which conform potential solutions for the NEWA project with the aim to fully exploit its capability jointly with MTI techniques.

Predictive ability of an early diagnostic guess in patients presenting with chest pain; a longitudinal descriptive study.

ABSTRACT: BACKGROUND: The intuitive early diagnostic guess could play an important role in reaching a final diagnosis. However, no study to date has attempted to quantify the importance of general practitioners' (GPs) ability to correctly appraise the origin of chest pain within the first minutes of an encounter. METHODS: The validation study was nested in a multicentre cohort study with a one year follow-up and included 626 successive patients who presented with chest pain and were attended by 58 GPs in Western Switzerland. The early diagnostic guess was assessed prior to a patient's history being taken by a GP and was then compared to a diagnosis of chest pain observed over the next year. RESULTS: Using summary measures clustered at the GP's level, the early diagnostic guess was confirmed by further investigation in 51.0% (CI 95%; 49.4% to 52.5%) of patients presenting with chest pain. The early diagnostic guess was more accurate in patients with a life threatening illness (65.4%; CI 95% 64.5% to 66.3%) and in patients who did not feel anxious (62.9%; CI 95% 62.5% to 63.3%). The predictive abilities of an early diagnostic guess were consistent among GPs. CONCLUSIONS: The GPs early diagnostic guess was correct in one out of two patients presenting with chest pain. The probability of a correct guess was higher in patients with a life-threatening illness and in patients not feeling anxious about their pain.