79 research outputs found

    Geometry of Middle to Late Triassic extensional deformation pattern in the Cordillera del Viento (Southern Central Andes): A combined field and geophysical study

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    Combined field and gravimetric-magnetic data reveal a complex pattern of extensional structures superimposed to the late Carboniferous – Early Permian Gondwanan orogen at the inner sectors of the Southern Central Andes, in the westernmost part of the Chos Malal fold and thrust belt at the cordillera del Viento area. W-NW, NW basement structures of regional significance, segmented by minor NE structures are bounding Late Triassic depocenters and structural highs corresponding to the cordillera del Viento rifting, equivalent to the Precuyo cycle. A pattern of roughly N-S trending structures recognized in the field associated with Andean thrusts do not show evidences of previ­ous structural controls, as they cut the magnetic anomalies. Field observations show that W-NW, NW and NE normal structures control changes in Late Triassic sedimentary thicknesses and are associated with synextensional geometries. Our model indicates that Late Triassic rifting in the area would have had a regional W-NW to NW trend being segmented by minor NE structures. Both sets were reactivated dur­ing Andean times, acting W-NW and NW structures as transfer zones between decoupled contractional panels and NE structures as frontal contractional structures. N-S contractional structures did not respect rifting architecture cutting through the depocenters and occasionaly exhuming synextensional geometries.La combinacion de datos de campo, junto con magnéticos y gravimétricos, revelan un patrón complejo de estructuras sobreimpuestas al orógeno gondwánico (Carbonífero superior– Pérmico) en el sector interno de la faja plegada y corrida de los Andes Centrales australes, en el área de la cordillera del Viento. Estructuras de basamento W-NW, NW de significancia regional, segmentadas por estruturas menores NE están limitando depocentros y altos estructurales correspondientes al rifting del Triásico Superior de la cordillera del Viento, equivalente de las unidades del ciclo Precuyo. En el campo se reconoce además un patrón de estructuras de rumbo N, asociadas a fallas andinas que no muestran evidencias de un control estrutural previo, ya que las anomalías magnéticas están cortadas por éstas. Las observaciones de campo demuestran que tanto las estructuras W-NW y NW como las NE controlan cambios de espesor de los sedimentos del Triásico Superior y se asocian a geometrías sinextensionales. El modelo propuesto indica que el rifting del Triásico Superior podría haber tenido una geometría elongada según el patrón de estructuras identificadas W-NW a NW, segmentado por estructuras menores NE. Ambas muestran reactivación durante tiempos andinos, las primeras actuando como zonas de transferencia entre sectores que muestran diferentes grados y mecánicas de contracción y las últimas como estructuras frontales contraccionales. Las estructuras contraccionales de orientación N-S no respetan la arquitectura del rift triásico, cortando los depocentros y eventualmente exhumando geometrías sinextensionales

    Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre-versus Postmenopausal Women

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    Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet-(PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 x 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 x 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 x 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 x 10(6)/l, range 139-462, vs. 121 x 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 x 10(6)/l, range 182-551, vs. 137 x 10(6)/l, range 64-432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women. Copyright (C) 2012 S. Karger AG, Base

    Quality of medication use in primary care - mapping the problem, working to a solution: a systematic review of the literature

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    Background: The UK, USA and the World Health Organization have identified improved patient safety in healthcare as a priority. Medication error has been identified as one of the most frequent forms of medical error and is associated with significant medical harm. Errors are the result of the systems that produce them. In industrial settings, a range of systematic techniques have been designed to reduce error and waste. The first stage of these processes is to map out the whole system and its reliability at each stage. However, to date, studies of medication error and solutions have concentrated on individual parts of the whole system. In this paper we wished to conduct a systematic review of the literature, in order to map out the medication system with its associated errors and failures in quality, to assess the strength of the evidence and to use approaches from quality management to identify ways in which the system could be made safer. Methods: We mapped out the medicines management system in primary care in the UK. We conducted a systematic literature review in order to refine our map of the system and to establish the quality of the research and reliability of the system. Results: The map demonstrated that the proportion of errors in the management system for medicines in primary care is very high. Several stages of the process had error rates of 50% or more: repeat prescribing reviews, interface prescribing and communication and patient adherence. When including the efficacy of the medicine in the system, the available evidence suggested that only between 4% and 21% of patients achieved the optimum benefit from their medication. Whilst there were some limitations in the evidence base, including the error rate measurement and the sampling strategies employed, there was sufficient information to indicate the ways in which the system could be improved, using management approaches. The first step to improving the overall quality would be routine monitoring of adherence, clinical effectiveness and hospital admissions. Conclusion: By adopting the whole system approach from a management perspective we have found where failures in quality occur in medication use in primary care in the UK, and where weaknesses occur in the associated evidence base. Quality management approaches have allowed us to develop a coherent change and research agenda in order to tackle these, so far, fairly intractable problems

    Can Interactions between Timing of Vaccine-Altered Influenza Pandemic Waves and Seasonality in Influenza Complications Lead to More Severe Outcomes?

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    Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves

    Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

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    The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs

    Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

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    Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required

    Using a mHealth tutorial application to change knowledge and attitude of frontline health workers to Ebola virus disease in Nigeria: a before-and-after study

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    Background: The Ebola epidemic exposed the weak state of health systems in West Africa and their devastating effect on frontline health workers and the health of populations. Fortunately, recent reviews of mobile technology demonstrate that mHealth innovations can help alleviate some health system constraints such as balancing multiple priorities, lack of appropriate tools to provide services and collect data, and limited access to training in health fields such as mother and child health, HIV/AIDS and sexual and reproductive health. However, there is little empirical evidence of mHealth improving health system functions during the Ebola epidemic in West Africa. Methods: We conducted quantitative cross-sectional surveys in 14 health facilities in Ondo State, Nigeria, to assess the effect of using a tablet computer tutorial application for changing the knowledge and attitude of health workers regarding Ebola virus disease. Results: Of 203 participants who completed pre- and post-intervention surveys, 185 people (or 91%) were female, 94 participants (or 46.3%) were community health officers, 26 people (13 %) were nurses/midwives, 8 people (or 4%) were laboratory scientists and 75 people (37%) belonged to a group called others. Regarding knowledge of Ebola: 178 participants (or 87.7%) had foreknowledge of Ebola before the study. Further analysis showed an 11% improvement in average knowledge levels between pre- and post-intervention scores with statistically significant differences (P < 0.05) recorded for questions concerning the transmission of the Ebola virus among humans, common symptoms of Ebola fever and whether Ebola fever was preventable. Additionally, there was reinforcement of positive attitudes of avoiding the following: contact with Ebola patients, eating bush meat and risky burial practices as indicated by increases between pre- and post-intervention scores from 83 to 92%, 57 to 64% and 67 to 79%, respectively. Moreover, more participants (from 95 to 97%) reported a willingness to practice frequent hand washing and disinfecting surfaces and equipment following the intervention, and more health workers were willing (from 94 to 97%) to use personal protective equipment to prevent the transmission of Ebola. Conclusions: The modest improvements in knowledge and reported attitudinal change toward Ebola virus disease suggests mHealth tutorial applications could hold promise for training health workers and building resilient health systems to respond to epidemics in West Africa
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