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Applicability of Winthrop Score for the Diagnosis of Influenza A in the Emergency Department of Hospital Pablo Arturo Suárez, January to March of 2018
Introduction: In 2010, the Department of Infectious Diseases at Winthrop University Hospital designed a score system for the diagnosis of Legionella pneumonia. In this study, we applied the score to patients with acute respiratory symptoms suspected of having type A influenza. The identification of patients at medium to high risk of Influenza A allows for early initiation of treatment.Objective: To study the applicability of the Winthrop score for the diagnosis of Influenza A.Methodology: A prospective cohort study was performed in 2018 at Hospital Pablo Arturo Suárez, in Quito, Ecuador. Patients 0 to 100 years old presenting to the emergency department with influenza-like illness in January-March of 2018 were included in the study. Winthrop score results were then compared with the result of the reverse transcription polymerase chain reaction (RT-PCR) for influenza A, the gold standard for diagnosis. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were used to establish the diagnostic performance of this point system for influenza A within the sample at large and in subgroup analyses by age (<5 years, 5-65 years, and >65 years) and comorbidities.Results: 149 patients were enrolled in the study period. The study population included 81 males (54.4%) and the majority of patients were less than 5 years of age (N=85, 57.0%). Furthermore, almost one-third of the patients were less than one year old (N=38, 25.5%). According to the Winthrop point system, 68.5% of the cases had a low probability of having influenza (n = 102), 8.7% of cases had a medium probability (n = 13) and 22.8 % of cases had a high probability (n = 34). The RT-PCR test for influenza was positive for 26.2% of patients (n = 39). The Winthrop point system had a sensitivity of 97.4%, specificity of 91.8%, positive predictive value of 80.8%, negative predictive value of 99.0%, positive likelihood ratio of 11.9, and negative likelihood ratio of 35.8 in the total study population. For children under 5 years, a sensitivity of 100%, specificity of 96.3%, positive predictive value of 77.7%, negative predictive value of 100%, positive likelihood ratio of 27, and negative likelihood ratio of 0. In patients older than 6 years, a sensitivity of 96.9%, specificity of 89%, positive predictive value of 84.21%, negative predictive value of 98%, positive likelihood ratio of 8.8, and negative likelihood ratio of 29.4. Testing in patients over 65 years had a sensitivity of 100%, specificity of 90%, positive predictive value of 87.5%, negative predictive value of 100%, positive likelihood ratio of 10 and negative likelihood ratio of 0. Finally, patients with comorbidities had a sensitivity of 90%, specificity of 88.24%, positive predictive value of 81.82%, negative predictive value of 93.75%, positive likelihood ratio of 7.65, and negative likelihood ratio of 8.82.Conclusions: The Winthrop score performed well in predicting Influenza A in patients with acute respiratory symptoms. This score may be useful in settings were Influenza A PCR testing is unavailable
Lecitase ultra: A phospholipase with great potential in biocatalysis
Lecitase Ultra is a chimera produced by the fusion of the genes of the lipase from Thermomyces lanuginosus and the phospholipase A1 from Fusarium oxysporum. The enzyme was first designed for the enzymatic degumming of oils, as that problem was not fully resolved before. It is commercialized only as an enzyme solution by Novo Nordisk A/S. This review shows the main uses of this promising enzyme. Starting from the original degumming use, the enzyme has found applications in many other food modification applications, like production of structured phospholipids (e.g., derivatives of phosphatidylcholine), tuning the properties of flour, etc. Moreover, the enzyme has been used in fine chemistry (resolution of racemic mixtures), in the production of aromas and fragrances, polymers modification, etc. Some papers show the use of the enzyme in biodiesel production. Moreover, we present the different technologies applied to obtain a suitable immobilized biocatalyst, remarking the immobilization via interfacial activation and how heterofunctional acyl supports may solve some of the limitations. Immobilized enzyme physical and chemical modifications have also been presented. Finally, Lecitase Ultra has been one of the model enzymes in a new strategy to coimmobilize lipases and other less stable enzymes.We gratefully recognize the financial support from MINECO from Spanish Government (project number CTQ2017-86170-R), Colciencias, Ministerio de Educación Nacional, Ministerio de Industria, Comercio y Turismo e ICETEX, Convocatoria Ecosistema Científico – Colombia Científica. Fondo Francisco José de Caldas, Contrato RC-FP44842-212-2018, Colciencias (Colombia, project number FP 44842-076-2016), Generalitat Valenciana (PROMETEO/2018/076), FAPERGS (project number 17/2551-0000939-8), FUNCAP (project number BP3-0139-00005.01.00/18) and CONACYT (Mexico, project number CB-2016-01, 286992)
Counterfeit medicines: a pilot study for chemical profiling employing a different proposal of an usual technique
Gas chromatography (GC) is a gold standard technique used in forensic laboratories, including for the characterization of counterfeit medicines. When coupled simultaneously to flame ionization (FID) and mass detector (MS) allow the identification and quantification of medicines and drugs employing a single method, besides permitting the application of chemometric tools for forensic intelligence purposes. Here is presented a pilot project that developed and applied a qualitative method for the analysis of counterfeit medicines comprised by amphetamine-type stimulants and antidepressants, through a simple extraction procedure followed by GC-FID/MS analysis, with application of exploratory tools by Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA). The main purpose was to identify similarities between the all compounds detected in the irregular medicines allowing the traceability of illicit producers with the creation of a common data base. Through the analyses it was verified that different producers of counterfeit medicines labeled as Sibutramine, added a mixture of Caffeine and Benzocaine in their formulation, respecting the same ratio of 2.2:1. HCA was able to confirm these results, showing the presence of both falsifications in the same cluster, representing the best tool to identify similar characteristics among the samples – when compared to PCA. Other interesting finding was the use of Fluoxetine as a falsification of counterfeit medicines labeled as Sibutramine and Diethylpropion. Another seized sample labeled as “Nobesio Forte”, marketed as a mix of stimulants, showed only Caffeine and Lidocaine in its formulation. The pilot project applied primarily to 45 samples of counterfeit medicines containing amphetamine-type stimulants and antidepressants, showed the capability of perform the chemical profiling of counterfeit medicines in the solid form - powder, capsules and tablets. Further analysis can be performed for different types of medicines in solid form using the developed method, allowing the construction of a single database to perform the chemical profiling of counterfeit medicines, enabling the traceability of illicit producers
Analytical and discrete solutions for the incipient motion of ellipsoidal sediment particles
[EN] This work introduces analytical and numerical approaches to compute the incipient motion of ellipsoidal sediment particles. Initiation of motion of spherical particles is dominated by rolling mode. However, solutions for initiation of motion for non-spherical grains have to incorporate rolling, sliding, and mixed modes. The proposed approaches include a wide variety of shapes and inclinations that represent realistic configurations of sediment bed layers. The numerical procedure is based on the discrete element method, simulating the micro-mechanics of the sediment as an aggregate of rigid ellipsoids interacting by contact. The numerical solution covers a range of incipient movements that cannot be covered by the analytical approach. Hence, some trapped modes observed in analytical calculations are complemented by the numerical computation of threshold stresses. The main results are organized as novel extended Shields diagrams for non-spherical grains, where non-dimensional critical shear stress is represented in terms of friction Reynolds number.This work was supported by the Ministerio de Ciencia e Innovación Grant [#BIA-2012-32918 and #BIA-2015-64994-P (MINECO/FEDER)].Bravo, R.; Ortiz, P.; Pérez-Aparicio, JL. (2018). Analytical and discrete solutions for the incipient motion of ellipsoidal sediment particles. Journal of Hydraulic Research. 56(1):29-43. https://doi.org/10.1080/00221686.2017.1289263S2943561Belytschko, T., & Neal, M. O. (1991). Contact-impact by the pinball algorithm with penalty and Lagrangian methods. International Journal for Numerical Methods in Engineering, 31(3), 547-572. doi:10.1002/nme.1620310309Bravo, R., Ortiz, P., & Pérez-Aparicio, J. L. (2014). Incipient sediment transport for non-cohesive landforms by the discrete element method (DEM). Applied Mathematical Modelling, 38(4), 1326-1337. doi:10.1016/j.apm.2013.08.010Bravo, R., Pérez-Aparicio, J. L., & Gómez-Hernández, J. J. (2015). Numerical sedimentation particle-size analysis using the Discrete Element Method. Advances in Water Resources, 86, 58-72. doi:10.1016/j.advwatres.2015.09.024Bravo, R., Pérez-Aparicio, J. L., & Laursen, T. A. (2012). An energy consistent frictional dissipating algorithm for particle contact problems. International Journal for Numerical Methods in Engineering, 92(9), 753-781. doi:10.1002/nme.4346Buffington, J. M., & Montgomery, D. R. (1997). A systematic analysis of eight decades of incipient motion studies, with special reference to gravel-bedded rivers. Water Resources Research, 33(8), 1993-2029. doi:10.1029/96wr03190Cheng, N.-S., & Chiew, Y.-M. (1999). Incipient sediment motion with upward seepage. Journal of Hydraulic Research, 37(5), 665-681. doi:10.1080/00221689909498522Chiew, Y.-M., & Parker, G. (1994). Incipient sediment motion on non-horizontal slopes. Journal of Hydraulic Research, 32(5), 649-660. doi:10.1080/00221689409498706Derksen, J. J. (2015). Simulations of granular bed erosion due to a mildly turbulent shear flow. Journal of Hydraulic Research, 53(5), 622-632. doi:10.1080/00221686.2015.1077354Dey, S. (1999). Sediment threshold. Applied Mathematical Modelling, 23(5), 399-417. doi:10.1016/s0307-904x(98)10081-1Dey, S. (2003). Threshold of sediment motion on combined transverse and longitudinal sloping beds. Journal of Hydraulic Research, 41(4), 405-415. doi:10.1080/00221680309499985Dey, S., Sarker, H. K. D., & Debnath, K. (1999). Sediment Threshold under Stream Flow on Horizontal and Sloping Beds. Journal of Engineering Mechanics, 125(5), 545-553. doi:10.1061/(asce)0733-9399(1999)125:5(545)Hölzer, A., & Sommerfeld, M. (2008). New simple correlation formula for the drag coefficient of non-spherical particles. Powder Technology, 184(3), 361-365. doi:10.1016/j.powtec.2007.08.021James, C. S. (1990). Prediction of entrainment conditions for nonuniform, noncohesive sediments. Journal of Hydraulic Research, 28(1), 25-41. doi:10.1080/00221689009499145Ji, C., Munjiza, A., Avital, E., Ma, J., & Williams, J. J. R. (2013). Direct numerical simulation of sediment entrainment in turbulent channel flow. Physics of Fluids, 25(5), 056601. doi:10.1063/1.4807075Klamkin, M. S. (1971). Elementary Approximations to the Area of N-Dimensional Ellipsoids. The American Mathematical Monthly, 78(3), 280. doi:10.2307/2317530Mandø, M., & Rosendahl, L. (2010). On the motion of non-spherical particles at high Reynolds number. Powder Technology, 202(1-3), 1-13. doi:10.1016/j.powtec.2010.05.001MILLER, M. C., McCAVE, I. N., & KOMAR, P. D. (1977). Threshold of sediment motion under unidirectional currents. Sedimentology, 24(4), 507-527. doi:10.1111/j.1365-3091.1977.tb00136.xWan Mohtar, W. H. M., & Munro, R. J. (2013). Threshold criteria for incipient sediment motion on an inclined bedform in the presence of oscillating-grid turbulence. Physics of Fluids, 25(1), 015103. doi:10.1063/1.4774341Ortiz, P., & Smolarkiewicz, P. K. (2006). Numerical simulation of sand dune evolution in severe winds. International Journal for Numerical Methods in Fluids, 50(10), 1229-1246. doi:10.1002/fld.1138Ortiz, P., & Smolarkiewicz, P. K. (2009). Coupling the dynamics of boundary layers and evolutionary dunes. Physical Review E, 79(4). doi:10.1103/physreve.79.041307Van Rijn, L. C. (1984). Sediment Transport, Part I: Bed Load Transport. Journal of Hydraulic Engineering, 110(10), 1431-1456. doi:10.1061/(asce)0733-9429(1984)110:10(1431)Shi, G.-H., & Goodman, R. E. (1985). Two dimensional discontinuous deformation analysis. International Journal for Numerical and Analytical Methods in Geomechanics, 9(6), 541-556. doi:10.1002/nag.1610090604Shields, A. (1936). 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Novozym 435 : the “perfect” lipase immobilized biocatalyst?
Novozym 435 (N435) is a commercially available immobilized lipase produced by Novozymes. It is based on immobilization via interfacial activation of lipase B from Candida antarctica on a resin, Lewatit VP OC 1600. This resin is a macroporous support formed by polyIJmethyl methacrylate) crosslinked with divinylbenzene. N435 is perhaps the most widely used commercial biocatalyst in both academy and industry. Here, we review some of the success stories of N435 (in chemistry, energy and lipid manipulation), but we focus on some of the problems that the use of this biocatalyst may generate. Some of these problems are just based on the mechanism of immobilization (interfacial activation) that may facilitate enzyme desorption under certain conditions. Other problems are specific to the support: mechanical fragility, moderate hydrophilicity that permits the accumulation of hydrophilic compounds (e.g., water or glycerin) and the most critical one, support dissolution in some organic media. Finally, some solutions (N435 coating with silicone, enzyme physical or chemical crosslinking, and use of alternative supports) are proposed. However, the N435 history, even with these problems, may continue in the coming future due to its very good properties if some simpler alternative biocatalysts are not developed
Identification of the presence of ischaemic stroke lesions by means of texture analysis on brain magnetic resonance images
Study funding This work was funded by the Row Fogo Charitable Trust (MVH, VGC) grant no. BRO-D.FID3668413, and the Wellcome Trust (patient recruitment, scanning, primary study Ref No. 088134/Z/09). The study was conducted independently of the funders who do not hold the data and did not participate in the study design or analyses. The Lothian Birth Cohort 1936 is funded by Age UK (Disconnected Mind grant) and the Medical Research Council (MRC; MR/M01311/1, G1001245, 82800), and the latter supported BSA. IJD was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology, which is funded by the MRC and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). David Moratal acknowledges financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER funds under Grant BFU2015-64380-C2-2-R, and from the Conselleria d'Educació, Investigació, Cultura i Esport, Generalitat Valenciana (grants AEST/2017/013 and AEST/2018/021). Rafael Ortiz-Ramón was supported by grant ACIF/2015/078 and grant BEFPI/2017/004 from the Conselleria d’Educació, Investigació, Cultura i Esport of the Valencian Community (Spain).Peer reviewedPublisher PD
Polyethylenimine: a very useful ionic polymer in the design of immobilized enzyme biocatalysts
This review discusses the possible roles of polyethylenimine (PEI) in the design of improved immobilized biocatalysts from diverse perspectives. This includes their use to activate supports and immobilize enzymes via ion exchange, as well as to improve immobilized enzymes by coating with PEI. PEI is a polymer containing primary, secondary and tertiary amino groups, having a strong anion exchange capacity under a broad range of conditions, and the capability to chemically react with different moieties on either an enzyme or a support. Also, as a multifunctional polymer, it has been modified stepwise to introduce different functionalities into the same polymer. This polymer (in combination with other anionic ones) permits the generation of “saline” environments around enzyme molecules, improving enzyme stability in the presence of hydrophobic compounds. The use of PEI as a physical glue useful to crosslink enzyme subunits in multimeric enzymes, monomeric enzymes immobilized via physical interactions or production of enzyme multilayers will be specially emphasized as new open avenues for enzyme coimmobilization. The coimmobilization of enzymes and cofactors using PEI may become one of the future developments allowed through an adequate use of this polymer and new pathways towards the design of enzyme combi-catalysts for their use in cascade reactions. Some unexplored but suggested uses derived from the properties of PEI are also proposed in the review, like the use of the buffering power of this multifunctional polymer to avoid pH gradients inside biocatalyst particles. Thus, although PEI has been a largely popular polymer in biocatalyst design, it looks like a long and in some cases almost unexplored road lies ahead.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) project number CTQ2013-41507-R, CNPq (process 403505/2013-5). A. B. M. thanks MINECO, Generalitat Valenciana and FEDER (CTQ2015-66080-R MINECO/FEDER and PROMETEOII/2014/010) for financial support
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