1,099 research outputs found

    Assessing architectural evolution: A case study

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    This is the post-print version of the Article. The official published can be accessed from the link below - Copyright @ 2011 SpringerThis paper proposes to use a historical perspective on generic laws, principles, and guidelines, like Lehman’s software evolution laws and Martin’s design principles, in order to achieve a multi-faceted process and structural assessment of a system’s architectural evolution. We present a simple structural model with associated historical metrics and visualizations that could form part of an architect’s dashboard. We perform such an assessment for the Eclipse SDK, as a case study of a large, complex, and long-lived system for which sustained effective architectural evolution is paramount. The twofold aim of checking generic principles on a well-know system is, on the one hand, to see whether there are certain lessons that could be learned for best practice of architectural evolution, and on the other hand to get more insights about the applicability of such principles. We find that while the Eclipse SDK does follow several of the laws and principles, there are some deviations, and we discuss areas of architectural improvement and limitations of the assessment approach

    Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

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    The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

    Dielectric 5-Branes and Giant Gravitons in ABJM

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    We construct a supersymmetric NS5-brane wrapped on a twisted 5-sphere expanding in the CP3CP^3 in AdS4×CP3AdS_4\times CP^3, with D0-brane charge. This configuration provides a realization of the stringy exclusion principle in terms of giant D0-branes. In the maximal case the twisted 5-sphere reduces to a CP2CP^2 and its energy can be accounted for both by a bound state of kk D4-branes wrapping the CP2CP^2 and a bound state of NN D0-branes, a realization on the gravity side of the symmetry of Young diagrams with NN rows and kk columns. We discuss some generalizations of this configuration in M-theory carrying angular momentum, some of them with an interpretation as giant gravitons. We provide the microscopical description that allows to explore the region of finite 't Hooft coupling.Comment: 26 pages, reference adde

    Slip and hall current effects on Jeffrey fluid suspension flow in a peristaltic hydromagnetic blood micropump

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    The magnetic properties of blood allow it to be manipulated with an electromagnetic field. Electromagnetic blood flow pumps are a robust technology which provide more elegant and sustainable performance compared with conventional medical pumps. Blood is a complex multi-phase suspension with non-Newtonian characteristics which are significant in micro-scale transport. Motivated by such applications, in the present article a mathematical model is developed for magnetohydrodynamic (MHD) pumping of blood in a deformable channel with peristaltic waves. A Jeffery’s viscoelastic formulation is employed for the rheology of blood. A twophase fluid-particle (“dusty”) model is utilized to better simulate suspension characteristics (plasma and erythrocytes). Hall current and wall slip effects are incorporated to achieve more realistic representation of actual systems. A two-dimensional asymmetric channel with dissimilar peristaltic wave trains propagating along the walls is considered. The governing conservation equations for mass, fluid and particle momentum are formulated with appropriate boundary conditions. The model is simplified using of long wavelength and creeping flow approximations. The model is also transformed from the fixed frame to the wave frame and rendered non-dimensional. Analytical solutions are derived. The resulting boundary value problem is solved analytically and exact expressions are derived for the fluid velocity, particulate velocity, fluid/particle fluid and particulate volumetric flow rates, axial pressure gradient, pressure rise and skin friction distributions are evaluated in detail. Increasing Hall current parameter reduces bolus growth in the channel, particle phase velocity and pressure difference in the augmented pumping region whereas it increases fluid phase velocity, axial pressure gradient and pressure difference in the pumping region. Increasing the hydrodynamic slip parameter accelerates both particulate and fluid phase flow at and close to the channel walls, enhances wall skin friction, boosts pressure difference in the augmented pumping region and increases bolus magnitudes. Increasing viscoelastic parameter (stress relaxation time to retardation time ratio) decelerates the fluid phase flow, accelerates the particle phase flow, decreases axial pressure gradient, elevates pressure difference in the augmented pumping region and reduces pressure difference in the pumping region. Increasing drag particulate suspension parameter decelerates the particle phase velocity, accelerates the fluid phase velocity, strongly elevates axial pressure gradient and reduces pressure difference (across one wavelength) in the augmented pumping region. Increasing particulate volume fraction density enhances bolus magnitudes in both the upper and lower zones of the channel and elevates pressure rise in the augmented pumping region

    Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

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    © 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia

    Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

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    Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge

    Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

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    Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development

    A spatiotemporal Data Envelopment Analysis (S-T DEA) approach:the need to assess evolving units

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    One of the major challenges in measuring efficiency in terms of resources and outcomes is the assessment of the evolution of units over time. Although Data Envelopment Analysis (DEA) has been applied for time series datasets, DEA models, by construction, form the reference set for inefficient units (lambda values) based on their distance from the efficient frontier, that is, in a spatial manner. However, when dealing with temporal datasets, the proximity in time between units should also be taken into account, since it reflects the structural resemblance among time periods of a unit that evolves. In this paper, we propose a two-stage spatiotemporal DEA approach, which captures both the spatial and temporal dimension through a multi-objective programming model. In the first stage, DEA is solved iteratively extracting for each unit only previous DMUs as peers in its reference set. In the second stage, the lambda values derived from the first stage are fed to a Multiobjective Mixed Integer Linear Programming model, which filters peers in the reference set based on weights assigned to the spatial and temporal dimension. The approach is demonstrated on a real-world example drawn from software development
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