Predictive validity of the CriSTAL tool for short-term mortality in older people presenting at Emergency Departments: a prospective study

© 2018, The Author(s). Abstract: To determine the validity of the Australian clinical prediction tool Criteria for Screening and Triaging to Appropriate aLternative care (CRISTAL) based on objective clinical criteria to accurately identify risk of death within 3 months of admission among older patients. Methods: Prospective study of ≥ 65 year-olds presenting at emergency departments in five Australian (Aus) and four Danish (DK) hospitals. Logistic regression analysis was used to model factors for death prediction; Sensitivity, specificity, area under the ROC curve and calibration with bootstrapping techniques were used to describe predictive accuracy. Results: 2493 patients, with median age 78–80 years (DK–Aus). The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% CI 7.7–8.6 vs. 5.8 95% CI 5.6–5.9) and Danish mean 7.1 (95% CI 6.6–7.5 vs. 5.5 95% CI 5.4–5.6). The model with Fried Frailty score was optimal for the Australian cohort but prediction with the Clinical Frailty Scale (CFS) was also good (AUROC 0.825 and 0.81, respectively). Values for the Danish cohort were AUROC 0.764 with Fried and 0.794 using CFS. The most significant independent predictors of short-term death in both cohorts were advanced malignancy, frailty, male gender and advanced age. CriSTAL’s accuracy was only modest for in-hospital death prediction in either setting. Conclusions: The modified CriSTAL tool (with CFS instead of Fried’s frailty instrument) has good discriminant power to improve prognostic certainty of short-term mortality for ED physicians in both health systems. This shows promise in enhancing clinician’s confidence in initiating earlier end-of-life discussions

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of Ilex laurina and Ilex paraguariensis on Colon Cancer Cells

Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells.Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic and antiproliferative effects were analyzed using MTT ((3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) and sulfhorodamine-B respectively. Cell death and apoptosis of human colon adenocarcinoma cells SW480 and their metastatic-derived SW620 cells, were analyzed by flow cytometry using propidium iodide and Annexin-V.Results: Although their flavonoid levels were similar, I. laurina infusion contained 2.2 and 4.4 times higher amounts of total phenolic and caffeoyl derivatives, respectively, than I. paraguariensis. FRAP and ORAC values for I. laurina infusion were 1.6 and 2.0 more active than I. paraguariensis. Both plant infusions inhibited viability and cell growth of SW480 and SW620 cells. These results may be associated to cell cycle-arrest and apoptosis because of the comparable increase of hypodiploid and annexin-V positive colon cancer cells.Conclusion: These data highlight the antioxidant and promising anticancer activities of I. laurina and Ilex paraguariensis.Keywords: Ilex laurina, Ilex paraguariensis, Antioxidant, Antiproliferative, Apoptosis, Colon cance

Solving Tree Problems with Category Theory

Artificial Intelligence (AI) has long pursued models, theories, and techniques to imbue machines with human-like general intelligence. Yet even the currently predominant data-driven approaches in AI seem to be lacking humans' unique ability to solve wide ranges of problems. This situation begs the question of the existence of principles that underlie general problem-solving capabilities. We approach this question through the mathematical formulation of analogies across different problems and solutions. We focus in particular on problems that could be represented as tree-like structures. Most importantly, we adopt a category-theoretic approach in formalising tree problems as categories, and in proving the existence of equivalences across apparently unrelated problem domains. We prove the existence of a functor between the category of tree problems and the category of solutions. We also provide a weaker version of the functor by quantifying equivalences of problem categories using a metric on tree problems.Comment: 10 pages, 4 figures, International Conference on Artificial General Intelligence (AGI) 201

Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L

[EN] Rhamnus ludovici-salvatoris, endemic to the Gymnesian Islands, coexists with the related and widespread R. alaternus in Mallorca and Menorca. In both species, the population genetic structure using RAPD, and flowering during a 3-year period to check for possible phenological barriers, were analyzed. Rhamnus ludovici-salvatoris showed lower genetic diversity and stronger population structure than R. alaternus, the Cabrera population being less diverse and the most differentiated. Rhamnus ludovici-salvatoris flowered one month later, although flowering of both species coincided sporadically. These congeners seem to have diverged through isolation by time and differentiation in habitat. The population genetic structure of R. ludovici-salvatoris could mainly be due to the existence of small populations on the one hand, and a gene flow caused by rare hybridization events on the other, which may also explain the presence of morphologically intermediate individuals in Menorca. The conservation of R. ludovici-salvatoris populations may include population reinforcements and other in situ interventions.Ferriol Molina, M.; Llorens García, L.; Gil, L.; Boira Tortajada, H. (2009). Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L. Plant Systematics and Evolution. 277(1-2):105-116. doi:10.1007/s00606-008-0110-3S1051162771-2Affre L, Thompson JD, Debussche M (1997) Genetic structure of continental and island populations of the Mediterranean endemic Cyclamen balearicum (Primulaceae). Amer J Bot 84(4): 437–451BOIB (2005) Decreto 75/2005. BOIB 106: 29–32Bolmgren K, Oxelman B (2004) Generic limits in Rhamnus L. s.l. (Rhamnaceae) inferred from nuclear and chloroplast DNA sequence phylogenies. Taxon 53(2):383–390Bolòs O, Molinier R (1958) Recherches phytosociologiques dans l’île de Majorque. 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Visualization and Analysis of 3D Microscopic Images

In a wide range of biological studies, it is highly desirable to visualize and analyze three-dimensional (3D) microscopic images. In this primer, we first introduce several major methods for visualizing typical 3D images and related multi-scale, multi-time-point, multi-color data sets. Then, we discuss three key categories of image analysis tasks, namely segmentation, registration, and annotation. We demonstrate how to pipeline these visualization and analysis modules using examples of profiling the single-cell gene-expression of C. elegans and constructing a map of stereotyped neurite tracts in a fruit fly brain

The Effects of Governmental Protected Areas and Social Initiatives for Land Protection on the Conservation of Mexican Amphibians

Traditionally, biodiversity conservation gap analyses have been focused on governmental protected areas (PAs). However, an increasing number of social initiatives in conservation (SICs) are promoting a new perspective for analysis. SICs include all of the efforts that society implements to conserve biodiversity, such as land protection, from private reserves to community zoning plans some of which have generated community-protected areas. This is the first attempt to analyze the status of conservation in Latin America when some of these social initiatives are included. The analyses were focused on amphibians because they are one of the most threatened groups worldwide. Mexico is not an exception, where more than 60% of its amphibians are endemic. We used a niche model approach to map the potential and real geographical distribution (extracting the transformed areas) of the endemic amphibians. Based on remnant distribution, all the species have suffered some degree of loss, but 36 species have lost more than 50% of their potential distribution. For 50 micro-endemic species we could not model their potential distribution range due to the small number of records per species, therefore the analyses were performed using these records directly. We then evaluated the efficiency of the existing set of governmental protected areas and established the contribution of social initiatives (private and community) for land protection for amphibian conservation. We found that most of the species have some proportion of their potential ecological niche distribution protected, but 20% are not protected at all within governmental PAs. 73% of endemic and 26% of micro-endemic amphibians are represented within SICs. However, 30 micro-endemic species are not represented within either governmental PAs or SICs. This study shows how the role of land conservation through social initiatives is therefore becoming a crucial element for an important number of species not protected by governmental PAs

Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study

[EN] Regulated expression of the Ena1 Na+-ATPase is a crucial event for adaptation to high salt and/or alkaline pH stress in the budding yeast Saccharomyces cerevisiae. ENA1 expression is under the control of diverse signaling pathways, including that mediated by the calcium-regulatable protein phosphatase calcineurin and its downstream transcription factor Crz1. We present here a quantitative study of the expression of Ena1 in response to alkalinization of the environment and we analyze the contribution of Crz1 to this response. Experimental data and mathematical models substantiate the existence of two stress-responsive Crz1-binding sites in the ENA1 promoter and estimate that the contribution of Crz1 to the early response of the ENA1 promoter is about 60%. The models suggest the existence of a second input with similar kinetics, which would be likely mediated by high pH-induced activation of the Snf1 kinase.This work was supported by grants BFU2011-30197-C3-01, BFU2014-54591-C2-1-P and EUI2009-04147 (SysMo2) to JA. (Ministry of Industry and Competitivity, Spain, and Fondo Europeo de Desarrollo Regional [FEDER]). JA is the recipient of an Ajut 2014SGR-4 award (Generalitat de Catalunya). DC was recipient of a predoctoral fellowship from the Spanish Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Petrezsélyová, S.; López-Malo, M.; Canadell, D.; Roque, A.; Serra-Cardona, A.; Marques Romero, MC.; Vilaprinyó, E.... (2016). Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study. PLoS ONE. 11(6):e0158424-e0158424. https://doi.org/10.1371/journal.pone.0158424Se0158424e015842411

Capability driven development: an approach to designing digital enterprises

The final publication is available at Springer via http://dx.doi.org/10.1007/s12599-014-0362-0[EN] The need for organizations to operate in changing environments is addressed by proposing an approach that integrates organizational development with information system (IS) development taking into account changes in the application context of the solution. This is referred to as Capability Driven Development (CDD). A meta-model representing business and IS designs consisting of goals, key performance indicators, capabilities, context and capability delivery patterns, is being proposed. The use of the meta-model is validated in three industrial case studies as part of an ongoing collaboration project, whereas one case is presented in the paper. Issues related to the use of the CDD approach, namely, CDD methodology and tool support are also discussed.This work has been partially supported by the EU-FP7 funded project no: 611351 CaaS - Capability as a Service in Digital Enterprises.Berzisa, S.; Bravos, G.; Cardona Gonzalez, T.; Czubayko, U.; España, S.; Grabis, J.; Henkel, M.... (2015). Capability driven development: an approach to designing digital enterprises. Business and Information Systems Engineering. 57(1):15-25. https://doi.org/10.1007/s12599-014-0362-0S1525571ArchiMate (2013) An enterprise modeling language from the Open Group. http://www.opengroup.org/archimate/ . Accessed 3 Dec 2014Asadi M, Ramsin R (2008) MDA-based methodologies: an analytical survey. In: Proceedings Model driven architecture – foundations and applications (ECMDA-FA 2008), LNCS 5095, pp 419–431Barney JB (1991) Firm resources and sustained competitive advantage. J Manag 17(1):99–120Bērziša S, Bravos G, Gonzalez Cardona T, Czubayko U, España S, Grabis J, Henke lM, Jokste L, Kampars J, Koc H, Kuhr J, Llorca C, Loucopoulos P, Juanes Pascua lR, Sandkuh lK, Simic H, Stirna J, Zdravkovic J (2014) Deliverable 1.4: Requirements specification for CDD, CaaS – capability as a service for digital enterprises. FP7 project no 611351, Riga Technical University, Latvia. Submitted for reviewBubenko JA Jr, Persson A, Stirna J (2001) User guide of the knowledge management approach using enterprise knowledge patterns. Deliverable D3, IST programme project hypermedia and pattern based knowledge management for smart organisations. project no. IST-2000-28401, Royal Institute of Technology, SwedenBriand LC, Yue T, Labiche Y (2011) A systematic review of transformation approaches between user requirements and analysis models. Requir Eng 16:75–99De Kinderen S, Gordijn J, Akkermans H (2009) Reasoning about customer needs in multi-supplier ICT service bundles using decision models. In: Proceedings 11th international conference on enterprise information systems (ICEIS 2009), pp 131–136Deloitte (2009) Cloud computing: forecasting change. Deloitte Consulting, New York. http://public.deloitte.no/dokumenter/2_Cloud_Computing%5B1%5D.pdf . Accessed 3 Dec 2014Dey A (2001) Understanding and using context. Pers Ubiquitous Comput 5(1):4–7Gamma E, Helm R, Johnson R, Vlissides J (1995) Design patterns: elements of reusable object-oriented software architecture. Addison-Wesley, BostonGomes D, Gonçalves JM, Santos R, Aguiar R (2010) XMPP based context management architecture. In: Proceedings GLOBECOM workshop, IEEE, pp 1372–1377González A, España S, Ruiz M, Pastor Ó (2011) Systematic derivation of class diagrams from communication-oriented business process models. In: 12th working conference on business process modeling, development, and support (BPMDS’11). Springer LNBIP 81, pp 246–260Henkel M, Stirna J (2010) Pondering on the key functionality of model driven development tools: the case of mendix. In: Forbrig P, Günther H (eds) Proceedings business informatics research (BIR 2010), Springer LNBIP 64, pp 146–160Hervas R, Bravo J, Fontecha J (2010) A context model based on ontological languages – a proposal for information visualisation. J Univers Comput Sci 16(12):1539–1555Jarke M, Loucopoulos P, Lyytinen K, Mylopoulos J, Robinson W (2011) The brave new world of design requirements. Information Syst 36(7):992–1008Kaplan RS, Norton DP (2004) Strategy maps: converting intangible assets into tangible outcomes. Harvard Business School Press, BostonKleppe A, Warmer J, Bast W (2013) MDA explained. Addison-Wesley, BostonLoniewski G, Insfran E, Abrahao L (2010) A systematic review of the use of requirements engineering techniques in model-driven development. In: Proceedings model driven engineering languages and systems (MODELS 2010), Part II, LNCS 6395, pp 213–227Mohagheghi P, Dehlen V (2008) Where is the proof? - a review of experiences from applying MDE in industry. In: Proceedings model driven architecture – foundations and applications (ECMDA-FA 2008). LNCS 5095. Springer, Heidelberg, pp 432–443Nilsson AG, Tolis C, Nellborn C (eds) (1999) Perspectives on business modelling: understanding and changing organisations. Springer, HeidelbergOASIS (2011) Reference architecture foundation for service oriented architecture version 1.0, committee specification draft 03/public review draft 02 06 July 2011. http://docs.oasis-open.org/soa-rm/soa-ra/v1.0/soa-ra.pdf . Accessed 3 Dec 2014OMG (2011a) UML superstructure. http://www.omg.org/spec/UML/2.4.1/ . Accessed 3 Dec 2014OMG (2011b) Business process model and notation. http://www.omg.org/spec/BPMN/2.0/ . Accessed 3 Dec 2014Osterwalder A, Pigneur Y (2003) Modeling value propositions in e-business. Proc 5th international conference on electronic commerce (ICEC 2003). ACM Conference Proceedings Series 50Papazoglou MP, Yang J (2002) Design methodology for web services and business processes. In: Proceedings 3rd international workshop on technologies for e-services (TES 03). LNCS 2444. Springer, Heidelberg, pp 54–64Pastor O, Giachetti G (2010) Linking goal-oriented requirements and model-driven development. In: Intentional perspectives on information systems engineering. Springer, Heidelberg, pp 257–276Porter ME (1985) Competitive advantage: creating and sustaining superior performance. Free Press, New YorkRuiz M, Costal D, España S, Franch X, Pastor Ó (2014) Integrating the goal and business process perspectives in information system analysis. 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IEEE, Venice, pp 261–266Wesenberg H (2011) Enterprise modeling in an agile world. In: Johannesson P, Krogstie J, Opdahl AL (eds) The practice of enterprise modeling (PoEM 2011). LNBIP 92. Springer, Heidelberg, pp 126–130Zdravkovic J, Stirna J, Henkel M, Grabis J (2013) Modeling business capabilities and context dependent delivery by cloud services. In: Proceedings advanced information systems engineering (CAiSE 2013). LNCS 7908. Springer, Heidelberg, pp 369–38

Mycobacterium tuberculosis Induces an Atypical Cell Death Mode to Escape from Infected Macrophages

BACKGROUND: Macrophage cell death following infection with Mycobacterium tuberculosis plays a central role in tuberculosis disease pathogenesis. Certain attenuated strains induce extrinsic apoptosis of infected macrophages but virulent strains of M. tuberculosis suppress this host response. We previously reported that virulent M. tuberculosis induces cell death when bacillary load exceeds approximately 20 per macrophage but the precise nature of this demise has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the characteristics of cell death in primary murine macrophages challenged with virulent or attenuated M. tuberculosis complex strains. We report that high intracellular bacillary burden causes rapid and primarily necrotic death via lysosomal permeabilization, releasing hydrolases that promote Bax/Bak-independent mitochondrial damage and necrosis. Cell death was independent of cathepsins B or L and notable for ultrastructural evidence of damage to lipid bilayers throughout host cells with depletion of several host phospholipid species. These events require viable bacteria that can respond to intracellular cues via the PhoPR sensor kinase system but are independent of the ESX1 system. CONCLUSIONS/SIGNIFICANCE: Cell death caused by virulent M. tuberculosis is distinct from classical apoptosis, pyroptosis or pyronecrosis. Mycobacterial genes essential for cytotoxicity are regulated by the PhoPR two-component system. This atypical death mode provides a mechanism for viable bacilli to exit host macrophages for spreading infection and the eventual transition to extracellular persistence that characterizes advanced pulmonary tuberculosis