Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

Meta Modeling for Business Process Improvement

Conducting business process improvement (BPI) initiatives is a topic of high priority for today’s companies. However, performing BPI projects has become challenging. This is due to rapidly changing customer requirements and an increase of inter-organizational business processes, which need to be considered from an end-to-end perspective. In addition, traditional BPI approaches are more and more perceived as overly complex and too resource-consuming in practice. Against this background, the paper proposes a BPI roadmap, which is an approach for systematically performing BPI projects and serves practitioners’ needs for manageable BPI methods. Based on this BPI roadmap, a domain-specific conceptual modeling method (DSMM) has been developed. The DSMM supports the efficient documentation and communication of the results that emerge during the application of the roadmap. Thus, conceptual modeling acts as a means for purposefully codifying the outcomes of a BPI project. Furthermore, a corresponding software prototype has been implemented using a meta modeling platform to assess the technical feasibility of the approach. Finally, the usability of the prototype has been empirically evaluated

Variable structure robot control systems: The RAPP approach

International audienceThis paper presents a method of designing variable structure control systems for robots. As the on-board robot computational resources are limited, but in some cases the demands imposed on the robot by the user are virtually limitless, the solution is to produce a variable structure system. The task dependent part has to be exchanged, however the task governs the activities of the robot. Thus not only exchange of some task-dependent modules is required, but also supervisory responsibilities have to be switched. Such control systems are necessary in the case of robot companions, where the owner of the robot may demand from it to provide many services.

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Euclid preparation. Measuring detailed galaxy morphologies for Euclid with Machine Learning

The Euclid mission is expected to image millions of galaxies with high resolution, providing an extensive dataset to study galaxy evolution. We investigate the application of deep learning to predict the detailed morphologies of galaxies in Euclid using Zoobot a convolutional neural network pretrained with 450000 galaxies from the Galaxy Zoo project. We adapted Zoobot for emulated Euclid images, generated based on Hubble Space Telescope COSMOS images, and with labels provided by volunteers in the Galaxy Zoo: Hubble project. We demonstrate that the trained Zoobot model successfully measures detailed morphology for emulated Euclid images. It effectively predicts whether a galaxy has features and identifies and characterises various features such as spiral arms, clumps, bars, disks, and central bulges. When compared to volunteer classifications Zoobot achieves mean vote fraction deviations of less than 12% and an accuracy above 91% for the confident volunteer classifications across most morphology types. However, the performance varies depending on the specific morphological class. For the global classes such as disk or smooth galaxies, the mean deviations are less than 10%, with only 1000 training galaxies necessary to reach this performance. For more detailed structures and complex tasks like detecting and counting spiral arms or clumps, the deviations are slightly higher, around 12% with 60000 galaxies used for training. In order to enhance the performance on complex morphologies, we anticipate that a larger pool of labelled galaxies is needed, which could be obtained using crowdsourcing. Finally, our findings imply that the model can be effectively adapted to new morphological labels. We demonstrate this adaptability by applying Zoobot to peculiar galaxies. In summary, our trained Zoobot CNN can readily predict morphological catalogues for Euclid images.Comment: 27 pages, 26 figures, 5 tables, submitted to A&

Confrontation of fibroblasts with cancer cells in vitro: Gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth

Background: There is growing evidence that emerging malignancies in solid tissues might be kept under control by physical intercellular contacts with normal fibroblasts. Methods: Here we characterize transcriptional landscapes of fibroblasts that confronted cancer cells. We studied four pairs of in vitro and ex vivo fibroblast lines which, within each pair, differed in their capacity to inhibit cancer cells. The natural process was modeled in vitro by confronting the fibroblasts with PC-3 cancer cells. Fibroblast transcriptomes were recorded by Affymetrix microarrays and then investigated using network analysis. Results: The network enrichment analysis allowed us to separate confrontation- and inhibition-specific components of the fibroblast transcriptional response. Confrontation-specific differences were stronger and were characterized by changes in a number of pathways, including Rho, the YAP/TAZ cascade, NF-kB, and TGF-beta signaling, as well as the transcription factor RELA. Inhibition-specific differences were more subtle and characterized by involvement of Rho signaling at the pathway level and by potential individual regulators such as IL6, MAPK8, MAP2K4, PRKCA, JUN, STAT3, and STAT5A. Conclusions: We investigated the interaction between cancer cells and fibroblasts in order to shed light on the potential mechanisms and explain the differential inhibitory capacity of the latter, which enabled both a holistic view on the process and details at the gene/protein level. The combination of our methods pointed to proteins, such as members of the Rho pathway, pro-inflammatory signature and the YAP1/TAZ cascade, that warrant further investigation via tools of experimental perturbation. We also demonstrated functional congruence between the in vitro and ex vivo models. © 2015 Alexeyenko et al

Euclid preparation XLIII. Measuring detailed galaxy morphologies for Euclid with machine learning

The Euclid mission is expected to image millions of galaxies at high resolution, providing an extensive dataset with which to study galaxy evolution. Because galaxy morphology is both a fundamental parameter and one that is hard to determine for large samples, we investigate the application of deep learning in predicting the detailed morphologies of galaxies in Euclid using Zoobot, a convolutional neural network pretrained with 450000 galaxies from the Galaxy Zoo project. We adapted Zoobot for use with emulated Euclid images generated based on Hubble Space Telescope COSMOS images and with labels provided by volunteers in the Galaxy Zoo: Hubble project. We experimented with different numbers of galaxies and various magnitude cuts during the training process. We demonstrate that the trained Zoobot model successfully measures detailed galaxy morphology in emulated Euclid images. It effectively predicts whether a galaxy has features and identifies and characterises various features, such as spiral arms, clumps, bars, discs, and central bulges. When compared to volunteer classifications, Zoobot achieves mean vote fraction deviations of less than 12% and an accuracy of above 91% for the confident volunteer classifications across most morphology types. However, the performance varies depending on the specific morphological class. For the global classes, such as disc or smooth galaxies, the mean deviations are less than 10%, with only 1000 training galaxies necessary to reach this performance. On the other hand, for more detailed structures and complex tasks, such as detecting and counting spiral arms or clumps, the deviations are slightly higher, of namely around 12% with 60000 galaxies used for training. In order to enhance the performance on complex morphologies, we anticipate that a larger pool of labelled galaxies is needed, which could be obtained using crowd sourcing. We estimate that, with our model, the detailed morphology of approximately 800 million galaxies of the Euclid Wide Survey could be reliably measured and that approximately 230 million of these galaxies would display features. Finally, our findings imply that the model can be effectively adapted to new morphological labels. We demonstrate this adaptability by applying Zoobot to peculiar galaxies. In summary, our trained Zoobot CNN can readily predict morphological catalogues for Euclid images

The Reciprocal Association between Fitness Indicators and Sleep Quality in the Context of Recent Sport Injury

The purpose of the study is to investigate whether the oxygen uptake and heart rate at rest, in Greek professional soccer players, are affected by recent injuries, as well as how sleep quality is affected. Forty-two male professional soccer players were included in the study and divided into two groups: injurygroup (n = 22, age: 21.6 &plusmn; 5.4 years, body fat: 11.0 &plusmn; 3.9%, total body water: 64.0 &plusmn; 2.5%) and no-injurygroup (n = 20, age: 24.2 &plusmn; 5.6 years, body fat: 10.1 &plusmn; 2.8%, total body water: 64.3 &plusmn; 1.8%). The oxygen uptake at rest (VO2resting, mL/min/kg) and heart rate (HR, bpm) were recorded in the upright position for 3 min, and the predicted values were calculated. One hour before, the athletes answered the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed a difference between groups (injurygroup vs. no-injurygroup) in VO2resting (7.5 &plusmn; 1.4 vs. 5.5 &plusmn; 1.2 mL/min/kg, p &lt; 0.001) and percent of predicted values (92.5 &plusmn; 17.2 vs. 68.3 &plusmn; 14.6%, p &lt; 0.001) and HR, such as beats per min (100.6 &plusmn; 12.8 vs. 93.1 &plusmn; 4.6 bpm, p = 0.001), percent of predicted values (50.7 &plusmn; 6.4 vs. 47.6 &plusmn; 2.8%, p = 0.003) and sleep quality score (PSQI: 4.9 &plusmn; 2.2 vs. 3.1 &plusmn; 0.9, p = 0.005). Anthropometric characteristics were not different between groups. Oxygen consumption and heart rate at rest are affected by the systemic adaptations due to injury. These pathophysiological changes probably relate to increased blood flow in an attempt to restore the injury area