Laccase-modified gold nanorods for electrocatalytic reduction of oxygen

The multicopper oxidase Trametes hirsuta laccase (ThLc) served as a bioelectrocatalyst on nanostructured cathodes. Nanostructuring was provided by gold nanorods (AuNRs), which were characterized and covalently attached to electrodes made of low-density graphite. The nanostructured electrode was the scaffold for covalent and oriented attachment of ThLc. The bioelectrocatalytic currents measured for oxygen reductionwere as high as 0.5 mA/cm2 and 0.7 mA/cm2, which were recorded under direct and mediated electron transfer regimes, respectively. The experimental data were fitted to mathematical models showing that when the O2 is bioelectroreduced at high rotation speed of the electrode the heterogeneous electron transfer step is the rateliming stage. The electrochemical measurement hints a wider population of non-optimally wired laccases than previously reported for 5-8 nmsize Au nanoparticle-modified electrode, which could be due to a larger size of the AuNRs when compared to the laccases as well as their different crystal facets. © 2015 Elsevier B.V.This work was funded by the Seventh Framework Programme (BIOENERGY FP7-PEOPLE-2013-607793 project).Peer Reviewe

Immunomodulatory properties of mesenchymal stem cells : a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005

Peer reviewedPublisher PD

pMineR: An Innovative R Library for Performing Process Mining in Medicine

Process Mining is an emerging discipline investigating tasks related with the automated identification of process models, given realworld data (Process Discovery). The analysis of such models can provide useful insights to domain experts. In addition, models of processes can be used to test if a given process complies (Conformance Checking) with specifications. For these capabilities, Process Mining is gaining importance and attention in healthcare. In this paper we introduce pMineR, an R library specifically designed for performing Process Mining in the medical domain, and supporting human experts by presenting processes in a human-readable way

Targeting the IL-6-Yap-Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis

ACKNOWLEDGEMENTS The authors thank staff at the University of Aberdeen’s Animal Facility, Microscopy and Histology Facility, qPCR Facility, and the Iain Fraser Cytometry Centre for their expert support. The authors also thank the NHS Grampian Biorepository for facilitating the collection of human tissue samples. Additionally, thanks is given to Denis Evseenko for critical review of the manuscript. Funding This work was supported by funding from the Medical Research Council (grants MR/L020211/1, MR/L022893/1), Versus Arthritis (formerly Arthritis Research UK, grants 20775, 19429, 21156, 20050, 19667, 20865, 21800), Tenovus Scotland (grant G13/14), and European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska Curie (Grant 642414).Peer reviewedPublisher PD

What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

[EN] In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?Gatta, R.; Vallati, M.; Fernández Llatas, C.; Martinez-Millana, A.; Orini, S.; Sacchi, L.; Lenkowicz, J.... (2020). What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper. International Journal of Environmental research and Public Health (Online). 17(18):1-19. https://doi.org/10.3390/ijerph17186616S1191718Guyatt, G. (1992). Evidence-Based Medicine. JAMA, 268(17), 2420. doi:10.1001/jama.1992.03490170092032Hripcsak, G., Ludemann, P., Pryor, T. A., Wigertz, O. B., & Clayton, P. D. (1994). Rationale for the Arden Syntax. Computers and Biomedical Research, 27(4), 291-324. doi:10.1006/cbmr.1994.1023Peleg, M. (2013). Computer-interpretable clinical guidelines: A methodological review. 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BMJ, 336(7650), 924-926. doi:10.1136/bmj.39489.470347.adHill, J., Bullock, I., & Alderson, P. (2011). A Summary of the Methods That the National Clinical Guideline Centre Uses to Produce Clinical Guidelines for the National Institute for Health and Clinical Excellence. Annals of Internal Medicine, 154(11), 752. doi:10.7326/0003-4819-154-11-201106070-00007Qaseem, A. (2012). Guidelines International Network: Toward International Standards for Clinical Practice Guidelines. Annals of Internal Medicine, 156(7), 525. doi:10.7326/0003-4819-156-7-201204030-00009Rosenfeld, R. M., Nnacheta, L. C., & Corrigan, M. D. (2015). Clinical Consensus Statement Development Manual. Otolaryngology–Head and Neck Surgery, 153(2_suppl), S1-S14. doi:10.1177/0194599815601394De Boeck, K., Castellani, C., & Elborn, J. S. (2014). Medical consensus, guidelines, and position papers: A policy for the ECFS. Journal of Cystic Fibrosis, 13(5), 495-498. doi:10.1016/j.jcf.2014.06.012Clinical Practical Guidelineshttp://www.openclinical.org/guidelines.htmlHaynes, A. B., Weiser, T. G., Berry, W. R., Lipsitz, S. R., Breizat, A.-H. S., Dellinger, E. P., … Gawande, A. A. (2009). A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population. New England Journal of Medicine, 360(5), 491-499. doi:10.1056/nejmsa0810119Grigg, E. (2015). Smarter Clinical Checklists. Anesthesia & Analgesia, 121(2), 570-573. doi:10.1213/ane.0000000000000352Hales, B., Terblanche, M., Fowler, R., & Sibbald, W. (2007). Development of medical checklists for improved quality of patient care. International Journal for Quality in Health Care, 20(1), 22-30. doi:10.1093/intqhc/mzm062Greenfield, S. (2017). Clinical Practice Guidelines. JAMA, 317(6), 594. doi:10.1001/jama.2016.19969Vegting, I. L., van Beneden, M., Kramer, M. H. H., Thijs, A., Kostense, P. J., & Nanayakkara, P. W. B. (2012). How to save costs by reducing unnecessary testing: Lean thinking in clinical practice. European Journal of Internal Medicine, 23(1), 70-75. doi:10.1016/j.ejim.2011.07.003Drummond, M. (2016). Clinical Guidelines: A NICE Way to Introduce Cost-Effectiveness Considerations? Value in Health, 19(5), 525-530. doi:10.1016/j.jval.2016.04.020Prior, M., Guerin, M., & Grimmer-Somers, K. (2008). The effectiveness of clinical guideline implementation strategies - a synthesis of systematic review findings. Journal of Evaluation in Clinical Practice, 14(5), 888-897. doi:10.1111/j.1365-2753.2008.01014.xWatts, C. G., Dieng, M., Morton, R. L., Mann, G. J., Menzies, S. W., & Cust, A. E. (2014). Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. British Journal of Dermatology, 172(1), 33-47. doi:10.1111/bjd.13403Woolf, S., Schünemann, H. J., Eccles, M. P., Grimshaw, J. M., & Shekelle, P. (2012). Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations. Implementation Science, 7(1). doi:10.1186/1748-5908-7-61Legido-Quigley, H., Panteli, D., Brusamento, S., Knai, C., Saliba, V., Turk, E., … Busse, R. (2012). Clinical guidelines in the European Union: Mapping the regulatory basis, development, quality control, implementation and evaluation across member states. Health Policy, 107(2-3), 146-156. doi:10.1016/j.healthpol.2012.08.004Rashidian, A., Eccles, M. P., & Russell, I. (2008). Falling on stony ground? A qualitative study of implementation of clinical guidelines’ prescribing recommendations in primary care. Health Policy, 85(2), 148-161. doi:10.1016/j.healthpol.2007.07.011Yang, W.-S., & Hwang, S.-Y. (2006). A process-mining framework for the detection of healthcare fraud and abuse. Expert Systems with Applications, 31(1), 56-68. doi:10.1016/j.eswa.2005.09.003Kose, I., Gokturk, M., & Kilic, K. (2015). An interactive machine-learning-based electronic fraud and abuse detection system in healthcare insurance. Applied Soft Computing, 36, 283-299. doi:10.1016/j.asoc.2015.07.018Pryor, T. A., Gardner, R. M., Clayton, P. D., & Warner, H. R. (1983). The HELP system. Journal of Medical Systems, 7(2), 87-102. doi:10.1007/bf00995116Shahar, Y., Miksch, S., & Johnson, P. (1998). The Asgaard project: a task-specific framework for the application and critiquing of time-oriented clinical guidelines. Artificial Intelligence in Medicine, 14(1-2), 29-51. doi:10.1016/s0933-3657(98)00015-3Boxwala, A. A., Peleg, M., Tu, S., Ogunyemi, O., Zeng, Q. T., Wang, D., … Shortliffe, E. H. (2004). GLIF3: a representation format for sharable computer-interpretable clinical practice guidelines. Journal of Biomedical Informatics, 37(3), 147-161. doi:10.1016/j.jbi.2004.04.002Terenziani, P., Molino, G., & Torchio, M. (2001). A modular approach for representing and executing clinical guidelines. Artificial Intelligence in Medicine, 23(3), 249-276. doi:10.1016/s0933-3657(01)00087-2Sutton, D. R., & Fox, J. (2003). The Syntax and Semantics of the PROformaGuideline Modeling Language. Journal of the American Medical Informatics Association, 10(5), 433-443. doi:10.1197/jamia.m1264Musen, M. A., Tu, S. W., Das, A. K., & Shahar, Y. (1996). EON: A Component-Based Approach to Automation of Protocol-Directed Therapy. Journal of the American Medical Informatics Association, 3(6), 367-388. doi:10.1136/jamia.1996.97084511Ciccarese, P., Caffi, E., Quaglini, S., & Stefanelli, M. (2005). Architectures and tools for innovative Health Information Systems: The Guide Project. International Journal of Medical Informatics, 74(7-8), 553-562. doi:10.1016/j.ijmedinf.2005.02.001Shiffman, R. N., & Greenes, R. A. (1994). Improving Clinical Guidelines with Logic and Decision-table Techniques. Medical Decision Making, 14(3), 245-254. doi:10.1177/0272989x9401400306Peleg, M., Tu, S., Bury, J., Ciccarese, P., Fox, J., Greenes, R. A., … Stefanelli, M. (2003). Comparing Computer-interpretable Guideline Models: A Case-study Approach. Journal of the American Medical Informatics Association, 10(1), 52-68. doi:10.1197/jamia.m1135Karadimas, H., Ebrahiminia, V., & Lepage, E. (2018). User-defined functions in the Arden Syntax: An extension proposal. Artificial Intelligence in Medicine, 92, 103-110. doi:10.1016/j.artmed.2015.11.003Peleg, M., Keren, S., & Denekamp, Y. (2008). Mapping computerized clinical guidelines to electronic medical records: Knowledge-data ontological mapper (KDOM). Journal of Biomedical Informatics, 41(1), 180-201. doi:10.1016/j.jbi.2007.05.003German, E., Leibowitz, A., & Shahar, Y. (2009). An architecture for linking medical decision-support applications to clinical databases and its evaluation. Journal of Biomedical Informatics, 42(2), 203-218. doi:10.1016/j.jbi.2008.10.007Marcos, M., Maldonado, J. A., Martínez-Salvador, B., Boscá, D., & Robles, M. (2013). Interoperability of clinical decision-support systems and electronic health records using archetypes: A case study in clinical trial eligibility. Journal of Biomedical Informatics, 46(4), 676-689. doi:10.1016/j.jbi.2013.05.004Marco-Ruiz, L., Moner, D., Maldonado, J. A., Kolstrup, N., & Bellika, J. G. (2015). Archetype-based data warehouse environment to enable the reuse of electronic health record data. International Journal of Medical Informatics, 84(9), 702-714. doi:10.1016/j.ijmedinf.2015.05.016Gooch, P., & Roudsari, A. (2011). Computerization of workflows, guidelines, and care pathways: a review of implementation challenges for process-oriented health information systems. Journal of the American Medical Informatics Association, 18(6), 738-748. doi:10.1136/amiajnl-2010-000033Quaglini, S., Stefanelli, M., Cavallini, A., Micieli, G., Fassino, C., & Mossa, C. (2000). Guideline-based careflow systems. Artificial Intelligence in Medicine, 20(1), 5-22. doi:10.1016/s0933-3657(00)00050-6Schadow, G., Russler, D. C., & McDonald, C. J. (2001). Conceptual alignment of electronic health record data with guideline and workflow knowledge. International Journal of Medical Informatics, 64(2-3), 259-274. doi:10.1016/s1386-5056(01)00196-4González-Ferrer, A., ten Teije, A., Fdez-Olivares, J., & Milian, K. (2013). Automated generation of patient-tailored electronic care pathways by translating computer-interpretable guidelines into hierarchical task networks. Artificial Intelligence in Medicine, 57(2), 91-109. doi:10.1016/j.artmed.2012.08.008Shabo, A., Parimbelli, E., Quaglini, S., Napolitano, C., & Peleg, M. (2016). Interplay between Clinical Guidelines and Organizational Workflow Systems. Methods of Information in Medicine, 55(06), 488-494. doi:10.3414/me16-01-0006Mulyar, N., van der Aalst, W. M. P., & Peleg, M. (2007). A Pattern-based Analysis of Clinical Computer-interpretable Guideline Modeling Languages. Journal of the American Medical Informatics Association, 14(6), 781-787. doi:10.1197/jamia.m2389Grando, M. A., Glasspool, D., & Fox, J. (2012). A formal approach to the analysis of clinical computer-interpretable guideline modeling languages. Artificial Intelligence in Medicine, 54(1), 1-13. doi:10.1016/j.artmed.2011.07.001Kaiser, K., & Marcos, M. (2015). Leveraging workflow control patterns in the domain of clinical practice guidelines. BMC Medical Informatics and Decision Making, 16(1). doi:10.1186/s12911-016-0253-zMartínez-Salvador, B., & Marcos, M. (2016). Supporting the Refinement of Clinical Process Models to Computer-Interpretable Guideline Models. Business & Information Systems Engineering, 58(5), 355-366. doi:10.1007/s12599-016-0443-3Decision Model and Notation Version 1.0https://www.omg.org/spec/DMN/1.0Ghasemi, M., & Amyot, D. (2016). Process mining in healthcare: a systematised literature review. International Journal of Electronic Healthcare, 9(1), 60. doi:10.1504/ijeh.2016.078745Rebuge, Á., & Ferreira, D. R. (2012). Business process analysis in healthcare environments: A methodology based on process mining. Information Systems, 37(2), 99-116. doi:10.1016/j.is.2011.01.003Rovani, M., Maggi, F. M., de Leoni, M., & van der Aalst, W. M. P. (2015). Declarative process mining in healthcare. Expert Systems with Applications, 42(23), 9236-9251. doi:10.1016/j.eswa.2015.07.040Rojas, E., Munoz-Gama, J., Sepúlveda, M., & Capurro, D. (2016). Process mining in healthcare: A literature review. Journal of Biomedical Informatics, 61, 224-236. doi:10.1016/j.jbi.2016.04.007Lenkowicz, J., Gatta, R., Masciocchi, C., Casà, C., Cellini, F., Damiani, A., … Valentini, V. (2018). Assessing the conformity to clinical guidelines in oncology. Management Decision, 56(10), 2172-2186. doi:10.1108/md-09-2017-0906Fernández-Llatas, C., Benedi, J.-M., García-Gómez, J., & Traver, V. (2013). Process Mining for Individualized Behavior Modeling Using Wireless Tracking in Nursing Homes. Sensors, 13(11), 15434-15451. doi:10.3390/s131115434Qu, G., Liu, Z., Cui, S., & Tang, J. (2013). Study on Self-Adaptive Clinical Pathway Decision Support System Based on Case-Based Reasoning. Frontier and Future Development of Information Technology in Medicine and Education, 969-978. doi:10.1007/978-94-007-7618-0_95Van de Velde, S., Roshanov, P., Kortteisto, T., Kunnamo, I., Aertgeerts, B., Vandvik, P. O., & Flottorp, S. (2015). Tailoring implementation strategies for evidence-based recommendations using computerised clinical decision support systems: protocol for the development of the GUIDES tools. Implementation Science, 11(1). doi:10.1186/s13012-016-0393-

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.</p> <p>Methods</p> <p>We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21–7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.</p> <p>Results</p> <p>Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71–5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4⁺T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4⁺T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).</p> <p>Conclusion</p> <p>Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.</p

IEA EBC Annex 72: Assessing Life Cycle Related Environmental Impacts Caused by Buildings: Guidelines for design decision-makers:Energy in Buildings and Communities Technology Collaboration Programme

The purpose of this report is to provide support to the design decisions-makers during the design process. For each of the defined design step decision the important topics to consider were identified, the key stakeholders are declared and the purpose of LCA at the selected design step is defined. The report covers: The definition of the design steps, the definition of the tasks in each design step and an overview of the relevant milestones for performing LCA; An overview of the systematic building decomposition methods and the appropriate levels at each design step; An overview of the tools that can be used for LCA and a selection process for choosing the right LCA tool. A special emphasize is given to the topic of Building Information Modelling (BIM), how the BIM tools can facilitate the LCA assessment and what information should be implemented in the BIM model; Strategies on how to reduce the design-related uncertainties; An overview of the visualization of the LCA results and which are appropriate in the selected design steps

On contractive cyclic fuzzy maps in metric spaces and some related results on fuzzy best proximity points and fuzzy fixed points

This paper investigates some properties of cyclic fuzzy maps in metric spaces. The convergence of distances as well as that of sequences being generated as iterates defined by a class of contractive cyclic fuzzy mapping to fuzzy best proximity points of (non-necessarily intersecting adjacent subsets) of the cyclic disposal is studied. An extension is given for the case when the images of the points of a class of contractive cyclic fuzzy mappings restricted to a particular subset of the cyclic disposal are allowed to lie either in the same subset or in its next adjacent one.The first author thanks the Spanish Ministry of Economy and Competitiveness for partial support of this work through Grant DPI2012-30651. He also thanks the Basque Government for its support through Grant IT378-10, and to the University of Basque Country by its support through Grant UFI 11/07

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe