Comparison of the efficacy and safety outcomes of edoxaban in 8040 women versus 13 065 men with atrial fibrillation in the ENGAGE AF-TIMI 48 trial.

BACKGROUND: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. METHODS: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis-defined major bleeding (safety). RESULTS: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P<0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69-1.11], men: HR, 0.87 [0.71-1.06]; P-interaction=0.97) and major bleeding (women: HR, 0.74 [0.59-0.92], men: HR, 0.84 [0.72-0.99]; P-interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15-0.59] versus HR, 0.70 [95% CI, 0.46-1.06]), intracranial bleeding (HR, 0.20 [95% CI, 0.10-0.39] versus HR, 0.63 [95% CI, 0.44-0.89]), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15-0.42] versus HR, 0.72 [95% CI, 0.54-0.96]) than men (each P-interaction<0.05). CONCLUSIONS: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes

Deep mantle roots and continental emergence: implications for whole-Earth elemental cycling, long-term climate, and the Cambrian explosion

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Effect of mechanical preconditioning on the electrical properties of knitted conductive textiles during cyclic loading

This paper presents, for the first time, the electrical response of knitted conductive fabrics to a considerable number of cycles of deformation in view of their use as wearable sensors. The changes in the electrical properties of four knitted conductive textiles, made of 20% stainless steel and 80% polyester fibers, were studied during unidirectional elongation in an Instron machine. Two tests sessions of 250 stretch–recovery cycles were conducted for each sample at two elongation rates (9.6 and 12 mm/s) and at three constant currents (1, 3 and 6 mA). The first session assessed the effects of an extended cyclic mechanical loading (preconditioning) on the electrical properties, especially on the electrical stabilization. The second session, which followed after a 5 minute interval under identical conditions, investigated whether the stabilization and repeatability of the electrical features were maintained after rest. The influence of current and elongation rate on the resistance measurements was also analyzed. In particular, the presence of a semiconducting behavior of the stainless steel fibers was proved by means of different test currents. Lastly, the article shows the time-dependence of the fabrics by means of hysteresis graphs and their non-linear behavior thanks to a time–frequency analysis. All knit patterns exhibited interesting changes in electrical properties as a result of mechanical preconditioning and extended use. For instance, the gauge factor, which indicates the sensitivity of the fabric sensor, varied considerably with the number of cycles, being up to 20 times smaller than that measured using low cycle number protocols

Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure

Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage

[EN] As a well established discipline and profession, project management has its distinctive tools and techniques. One of them that has been considered the embodiment of the core principles of project management is the Earned Value Management (EVM). In managing construction projects, the EVM has been considered as a suitable tool and hence, has been implemented in various construction industry but absent in some others. Taking into account the dynamic environment where construction companies have to operate, particularly in turbulence environments as the direct result of recent global economic downturn, this paper explores the potential implementation of EVM in one of the construction industry, the Spanish construction industry. The outcomes confirm the needs for and feasibility of implementing EVM as a structured approach in the industry to reposition the Spanish construction industry with the long term view to increase its project management maturity level as a pathway to gaining competitive advantage.Universitat Politecnica de Valencia [grant number 19701344]Sutrisna, M.; Pellicer, E.; Torres-Machí, C.; Picornell, M. (2018). Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage. International Journal of Construction Management. 20(1):1-12. https://doi.org/10.1080/15623599.2018.1459155S112201Anbari, F. T. (2004). Earned value project management method and extensions. IEEE Engineering Management Review, 32(3), 97-97. doi:10.1109/emr.2004.25113Aram, J. D., & Walochik, K. (1996). Improvisation and the Spanish Manager. International Studies of Management & Organization, 26(4), 73-89. doi:10.1080/00208825.1996.11656695Brandon, D. M. (1998). Implementing Earned Value Easily and Effectively. Project Management Journal, 29(2), 11-18. doi:10.1177/875697289802900204Brown, A., & Adams, J. (2000). Measuring the effect of project management on construction outputs: a new approach. International Journal of Project Management, 18(5), 327-335. doi:10.1016/s0263-7863(99)00026-5Bryde, D. J. (2003). Modelling project management performance. International Journal of Quality & Reliability Management, 20(2), 229-254. doi:10.1108/02656710310456635Chen, H. L., Chen, W. T., & Lin, Y. L. (2016). Earned value project management: Improving the predictive power of planned value. International Journal of Project Management, 34(1), 22-29. doi:10.1016/j.ijproman.2015.09.008De la Cruz, M. P., del Caño, A., & de la Cruz, E. (2006). Downside Risks in Construction Projects Developed by the Civil Service: The Case of Spain. Journal of Construction Engineering and Management, 132(8), 844-852. doi:10.1061/(asce)0733-9364(2006)132:8(844)Din, S., Abd-Hamid, Z., & Bryde, D. J. (2011). ISO 9000 certification and construction project performance: The Malaysian experience. International Journal of Project Management, 29(8), 1044-1056. doi:10.1016/j.ijproman.2010.11.001Eldin, N. N. (1989). Measurement of Work Progress: Quantitative Technique. Journal of Construction Engineering and Management, 115(3), 462-474. doi:10.1061/(asce)0733-9364(1989)115:3(462)Gidado, K. I. (1996). Project complexity: The focal point of construction production planning. Construction Management and Economics, 14(3), 213-225. doi:10.1080/014461996373476Hastak, M., Halpin, D. W., & Vanegas, J. (1996). COMPASS—New Paradigm for Project Cost Control Strategy and Planning. Journal of Construction Engineering and Management, 122(3), 254-264. doi:10.1061/(asce)0733-9364(1996)122:3(254)D. Holt, G., & S. Goulding, J. (2014). Conceptualisation of ambiguous-mixed-methods within building and construction research. Journal of Engineering, Design and Technology, 12(2), 244-262. doi:10.1108/jedt-02-2013-0020Ibbs, C. W., & Kwak, Y. H. (2000). Assessing Project Management Maturity. Project Management Journal, 31(1), 32-43. doi:10.1177/875697280003100106Jugdev, K., & Thomas, J. (2002). 2002 Student Paper Award Winner: Project Management Maturity Models: The Silver Bullets of Competitive Advantage? Project Management Journal, 33(4), 4-14. doi:10.1177/875697280203300402Kim, E., Wells, W. G., & Duffey, M. R. (2003). A model for effective implementation of Earned Value Management methodology. International Journal of Project Management, 21(5), 375-382. doi:10.1016/s0263-7863(02)00049-2Kim, T., Kim, Y.-W., & Cho, H. (2016). Customer Earned Value: Performance Indicator from Flow and Value Generation View. Journal of Management in Engineering, 32(1), 04015017. doi:10.1061/(asce)me.1943-5479.0000377Laufer, A., & Tucker, R. L. (1987). Is construction project planning really doing its job? A critical examination of focus, role and process. Construction Management and Economics, 5(3), 243-266. doi:10.1080/01446198700000023Liberatore, M. J., Pollack-Johnson, B., & Smith, C. A. (2001). Project Management in Construction: Software Use and Research Directions. Journal of Construction Engineering and Management, 127(2), 101-107. doi:10.1061/(asce)0733-9364(2001)127:2(101)Mir, F. A., & Pinnington, A. H. (2014). Exploring the value of project management: Linking Project Management Performance and Project Success. International Journal of Project Management, 32(2), 202-217. doi:10.1016/j.ijproman.2013.05.012Navon, R., & Haskaya, I. (2006). Is detailed progress monitoring possible without designated manual data collection? Construction Management and Economics, 24(12), 1225-1229. doi:10.1080/01446190600999097Onwuegbuzie, A. J., & Leech, N. L. (2005). Taking the «Q» Out of Research: Teaching Research Methodology Courses Without the Divide Between Quantitative and Qualitative Paradigms. Quality & Quantity, 39(3), 267-295. doi:10.1007/s11135-004-1670-0Oviedo-Haito, R. J., Jiménez, J., Cardoso, F. F., & Pellicer, E. (2014). Survival Factors for Subcontractors in Economic Downturns. Journal of Construction Engineering and Management, 140(3), 04013056. doi:10.1061/(asce)co.1943-7862.0000811Pellicer, E., Sanz, M. A., Esmaeili, B., & Molenaar, K. R. (2016). Exploration of Team Integration in Spanish Multifamily Residential Building Construction. Journal of Management in Engineering, 32(5), 05016012. doi:10.1061/(asce)me.1943-5479.0000438Potts, K., & Ankrah, N. (2008). Construction Cost Management. doi:10.4324/9780203933015Vanhoucke, M. (2012). Project Management with Dynamic Scheduling. doi:10.1007/978-3-642-25175-7Yazici, H. J. (2009). The Role of Project Management Maturity and Organizational Culture in Perceived Performance. Project Management Journal, 40(3), 14-33. doi:10.1002/pmj.20121Yu, A. G., Flett, P. D., & Bowers, J. A. (2005). Developing a value-centred proposal for assessing project success. International Journal of Project Management, 23(6), 428-436. doi:10.1016/j.ijproman.2005.01.00

Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection

Chronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis

Tailor-made inflammation: how neutrophil serine proteases modulate the inflammatory response

Neutrophil granulocytes are important mediators of innate immunity, but also participate in the pathogenesis of (auto)inflammatory diseases. Neutrophils express a specific set of proteolytic enzymes, the neutrophil serine proteases (NSPs), which are stored in cytoplasmic granules and can be secreted into the extra- and pericellular space upon cellular activation. These NSPs, namely cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3), have early been implicated in bacterial defense. However, NSPs also regulate the inflammatory response by specifically altering the function of cytokines and chemokines. For instance, PR3 and NE both inactivate the anti-inflammatory mediator progranulin, which may play a role in chronic inflammation. Here, we provide a concise update on NSPs as modulators of inflammation and discuss the biological and pathological significance of this novel function of NSPs. Mounting evidence support an important proinflammatory function for PR3, which may have been underestimated in the past