Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial

Aims: The LION-HEART study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Methods and results: Sixty-nine patients from 12 centres were randomly assigned at a 2: 1 ratio to levosimendan or placebo groups, receiving treatment by a 6-hour intravenous infusion (0.2 mu g/kg/min without bolus) every 2weeks for 12weeks. The primary endpoint was the effect on serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health-related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT-proBNP over time for patients who received levosimendan was significantly lower than for the placebo group {344 x 10(3) [95% confidence interval (CI) 283 x 10(3)-404 x 10(3)] vs. 535 x 10(3) [443 x 10(3)-626 x 10(3)], P = 0.003}. In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. Conclusions: In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT-proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials

Stability Analysis and Design of Negative Impedance Converters: Application to Circuit and Small Antennas

Negative impedance converters (NICs) have been proposed as structures to improve the performance of RF circuits and electrically small antennas. However, NICs suffer from stability problems. This paper presents a compact procedure to analyze the stability of NICs. Then, the required and sufficient conditions to predict the stability of a negative impedance converter are given. These conditions can be evaluated using standard computer-aided-design software. Finally, a NIC prototype is given to validate and illustrate the presented design procedure, it is also integrated with a printed, blade-type, electrically small monopole in the VHF ban

Case-Based Statistical Learning: A Non-Parametric Implementation with a Conditional-Error Rate SVM

© 2013 IEEE. Machine learning has been successfully applied to many areas of science and engineering. Some examples include time series prediction, optical character recognition, signal and image classification in biomedical applications for diagnosis and prognosis and so on. In the theory of semi-supervised learning, we have a training set and an unlabeled data, that are employed to fit a prediction model or learner, with the help of an iterative algorithm, such as the expectation-maximization algorithm. In this paper, a novel non-parametric approach of the so-called case-based statistical learning is proposed in a low-dimensional classification problem. This supervised feature selection scheme analyzes the discrete set of outcomes in the classification problem by hypothesis-testing and makes assumptions on these outcome values to obtain the most likely prediction model at the training stage. A novel prediction model is described in terms of the output scores of a confidence-based support vector machine classifier under class-hypothesis testing. To have a more accurate prediction by considering the unlabeled points, the distribution of unlabeled examples must be relevant for the classification problem. The estimation of the error rates from a well-trained support vector machines allows us to propose a non-parametric approach avoiding the use of Gaussian density function-based models in the likelihood ratio test

Evaluation of Textural and Sensory Properties on Typical Spanish Small Cakes Designed Using Alternative Flours

[EN] The objective of this study was to evaluate the effect of wheat flour substitution with toasted corn, quinoa, and sorghum flours on the overall perception and texture of typical Spanish small cakes named madeleine. In order to evaluate these characteristics, a texture profile analysis (TPA) and a sensory analysis were carried out. TPA showed that the replacement of wheat flour by sorghum flour did not affect significantly texture parameters of cakes. Hedonic sensory tests were also conducted revealing that the cake prepared with sorghum flour was highly appreciated by the consumers as it got scores similar to traditional cakes made with wheat flour.Casas Moreno, MDM.; Barreto Palacios, VJ.; González Carrascosa, R.; Iborra Bernad, MDC.; Andrés Bello, MD.; Martínez Monzó, J.; García-Segovia, P. (2015). Evaluation of Textural and Sensory Properties on Typical Spanish Small Cakes Designed Using Alternative Flours. Journal of Culinary Science and Technology. 13(1):19-28. doi:10.1080/15428052.2014.952475S1928131Baldwin, R. R., Baldry, R. P., & Johansen, R. G. (1972). Fat systems for bakery products. Journal of the American Oil Chemists’ Society, 49(8), 473-477. doi:10.1007/bf02582482Beleia, A., Miller, R. A., & Hoseney, R. C. (1996). Starch Gelatinization in Sugar Solutions. Starch - Starke, 48(7-8), 259-262. doi:10.1002/star.19960480705Brannan, G. L., Setser, C. S., Kemp, K. E., Seib, P. A., & Roozeboom, K. (2001). Sensory Characteristics of Grain Sorghum Hybrids with Potential for Use in Human Food. Cereal Chemistry Journal, 78(6), 693-700. doi:10.1094/cchem.2001.78.6.693Cauvain, S. P., & Young, L. S. (Eds.). (2006). Baked Products. doi:10.1002/9780470995907Chieh, C. (s. f.). Water. Bakery Products, 211-232. doi:10.1002/9780470277553.ch11Conforti, F. D. (s. f.). Cake Manufacture. Bakery Products, 393-410. doi:10.1002/9780470277553.ch22Ghotra, B. S., Dyal, S. D., & Narine, S. S. (2002). Lipid shortenings: a review. Food Research International, 35(10), 1015-1048. doi:10.1016/s0963-9969(02)00163-1Kiosseoglou, V., & Paraskevopoulou, A. (s. f.). Eggs. Bakery Products, 161-172. doi:10.1002/9780470277553.ch8Lai, H.-M., & Lin, T.-C. (s. f.). Bakery Products: Science and Technology. Bakery Products, 3-68. doi:10.1002/9780470277553.ch1Lau, M. ., Tang, J., & Paulson, A. . (2000). Texture profile and turbidity of gellan/gelatin mixed gels. Food Research International, 33(8), 665-671. doi:10.1016/s0963-9969(00)00111-3LINDLEY, M. G. (1987). Sucrose in baked products. Nutrition Bulletin, 12(1), 41-45. doi:10.1111/j.1467-3010.1987.tb00011.xMastromatteo, M., Chillo, S., Iannetti, M., Civica, V., & Del Nobile, M. A. (2011). Formulation optimisation of gluten-free functional spaghetti based on quinoa, maize and soy flours. International Journal of Food Science & Technology, 46(6), 1201-1208. doi:10.1111/j.1365-2621.2011.02613.xOreopoulou, V. (s. f.). Fat Replacers. Bakery Products, 193-210. doi:10.1002/9780470277553.ch10Peressini, D., Pin, M., & Sensidoni, A. (2011). Rheology and breadmaking performance of rice-buckwheat batters supplemented with hydrocolloids. Food Hydrocolloids, 25(3), 340-349. doi:10.1016/j.foodhyd.2010.06.012Sanz, T., Salvador, A., Baixauli, R., & Fiszman, S. M. (2009). Evaluation of four types of resistant starch in muffins. II. Effects in texture, colour and consumer response. European Food Research and Technology, 229(2), 197-204. doi:10.1007/s00217-009-1040-1Taylor, J. R. N., Schober, T. J., & Bean, S. R. (2006). Novel food and non-food uses for sorghum and millets. Journal of Cereal Science, 44(3), 252-271. doi:10.1016/j.jcs.2006.06.009Wilderjans, E., Luyts, A., Brijs, K., & Delcour, J. A. (2013). Ingredient functionality in batter type cake making. Trends in Food Science & Technology, 30(1), 6-15. doi:10.1016/j.tifs.2013.01.001Wilderjans, E., Pareyt, B., Goesaert, H., Brijs, K., & Delcour, J. A. (2008). The role of gluten in a pound cake system: A model approach based on gluten–starch blends. Food Chemistry, 110(4), 909-915. doi:10.1016/j.foodchem.2008.02.079Wilson, N. L. W. (2011). How the Cookie Crumbles: A Case Study of Gluten-Free Cookies and Random Utility. American Journal of Agricultural Economics, 94(2), 576-582. doi:10.1093/ajae/aar081Zhu, J.-H., Yang, X.-Q., Ahmad, I., Li, L., Wang, X.-Y., & Liu, C. (2008). Rheological properties of κ-carrageenan and soybean glycinin mixed gels. Food Research International, 41(3), 219-228. doi:10.1016/j.foodres.2007.11.00

Proteomic Analysis of the Cyst Stage of Entamoeba histolytica

We used tandem mass spectrometry to identify E. histolytica cyst proteins in 5 cyst positive stool samples. We report the identification of 417 non-redundant E. histolytica proteins including 195 proteins that were not identified in existing trophozoite derived proteome or EST datasets, consistent with cyst specificity. Because the cysts were derived directly from patient samples with incomplete purification, a limited number of proteins were identified (N = 417) that probably represent only a partial proteome. Nevertheless, the study succeeded in identifying proteins that are likely to be abundant in the cyst stage of the parasite. Several of these proteins may play roles in E. histolytica stage conversion or cyst function. Proteins identified in this study may be useful markers for diagnostic detection of E. histolytica cysts. Overall, the data generated in this study promises to aid the understanding of the cyst stage of the parasite which is vital for disease transmission and pathogenesis in E. histolytica

Modeling the clonal heterogeneity of stem cells

Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties

Cystic Echinococcosis in Spain: Current Situation and Relevance for Other Endemic Areas in Europe

Cystic echinococcosis (CE) remains an important health problem in many regions of the world, both where no control measures have been implemented, and where control programs have been incompletely successful with ensuing re-emergence of the disease. In Spain, official data on CE show an increase in the proportion of intermediate hosts with CE during the last few years, and autochthonous pediatric patients have been reported, a sign of active local transmission of disease. A similar picture emerges from data reported to the European Food Safety Authority by other European countries. Nevertheless, several crucial aspects related to CE that would help better understand and control the disease have not been tackled appropriately, in particular the emergence of infection in specific geographical areas. In this respect, while some data are missing, other data are conflicting because they come from different databases. We review the current situation of CE in Spain compared with areas in which similar problems in the CE field exist, and offer recommendations on how to overcome those limitations. Specifically, we believe that the introduction of national registries for CE with online data entry, following the example set by the European Registry for Alveolar Echinococcosis, would help streamline data collection on CE by eliminating the need for evaluating and integrating data from multiple regions, by avoiding duplication of data from patients who access several different health facilities over time, and by providing much needed clinical and epidemiological data that are currently accessible only to clinicians

The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

BACKGROUND: The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. METHODS: We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS: Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Computational Approaches to Explainable Artificial Intelligence:Advances in Theory, Applications and Trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9 International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications