125 research outputs found

    Mapping temporally-variable exposure to flooding in small Mediterranean basins using land-use indicators

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    This article deals with mapping exposure (or external vulnerability) to flood risk in two typical Mediterranean ephemeral streams: the Barranco de Carraixet and the Rambla de Poyo. The floodplains of both streams are within the metropolitan area of the city of Valencia (Spain"s third largest city). Following the Mediterranean model, they are very fertile areas (with intense periurban and highly productive agriculture) which have recently absorbed the great urban expansion of the metropolis. Hydrologically these basins remain dry for most of the year, but become particularly dangerous during flash-flood events. They generate a risk pattern highly dependent on exposure since, in general, the hazard factor is very difficult to map, given the unpredictable nature of flash-floods. This work constitutes a proof of concept based on simple estimators obtained from land uses. External vulnerability or exposure is evaluated as a function of economic land value and human exposure to hazard. Land value is directly taken from the cadastre whilst human exposure is indirectly estimated from the location of population in relation to timeeactivity profiles. The temporal dimension is introduced and three exposure scenarios have been mapped, related to different time periods: working days, nights, weekends and holidays. The results show different patterns of exposure for each plain. In Carraixet floodplain exposure is greater at night and on weekends and holidays than during working hours, on account of the dominant agricultural and residential land uses. In the Poyo plain there are no major contrasts in absolute terms between day and night time, although spatial patterns of exposure vary from day to night: during the day, exposure is higher in industrial and commercial areas (around communication routes) whilst at night residential areas show more exposure

    Framing vulnerability, risk and societal responses: the MOVE framework

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    The paper deals with the development of a general as well as integrative and holistic framework to systematize and assess vulnerability, risk and adaptation. The framework is a thinking tool meant as a heuristic that outlines key factors and different dimensions that need to be addressed when assessing vulnerability in the context of natural hazards and climate change. The approach underlines that the key factors of such a common framework are related to the exposure of a society or system to a hazard or stressor, the susceptibility of the system or community exposed, and its resilience and adaptive capacity. Additionally, it underlines the necessity to consider key factors and multiple thematic dimensions when assessing vulnerability in the context of natural and socio-natural hazards. In this regard, it shows key linkages between the different concepts used within the disaster risk management (DRM) and climate change adaptation (CCA) research. Further, it helps to illustrate the strong relationships between different concepts used in DRM and CCA. The framework is also a tool for communicating complexity and stresses the need for societal change in order to reduce risk and to promote adaptation. With regard to this, the policy relevance of the framework and first results of its application are outlined. Overall, the framework presented enhances the discussion on how to frame and link vulnerability, disaster risk, risk management and adaptation concepts

    Effect of Pritelivir Compared With Valacyclovir on Genital HSV-2 Shedding in Patients With Frequent Recurrences A Randomized Clinical Trial

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    Importance Current therapy of herpes infections relies on nucleoside analogues. Pritelivir is a well-tolerated novel herpes simplex virus (HSV) helicase-primase inhibitor that reduced genital shedding and lesions. Objective To compare the efficacy of pritelivir with valacyclovir for suppression of genital HSV-2 infection. Design, Setting, and Participants A phase 2, randomized, double-blind, crossover clinical trial at clinical research centers in 4 US cities (October 2012-July 2013) compared daily oral doses of 100 mg of pritelivir with 500 mg of valacyclovir. The planned sample size was 98 adults, allowing for detection of a 50% reduction in viral shedding between the study treatments. Healthy adults with 4 to 9 annual genital HSV-2 recurrences were eligible. Ninety-one participants were randomized: 45 to receive pritelivir and 46 to receive valacyclovir first when the US Food and Drug Administration placed the trial on clinical hold based on findings in a concurrent nonclinical toxicity study, and the sponsor terminated the study. Interventions Participants took the first drug for 28 days followed by 28 days of washout before taking the second drug for 28 days. Throughout treatment, the participants collected genital swabs 4 times daily for testing by HSV polymerase chain reaction assays. Main Outcomes and Measures The primary end point was within-participant genital HSV shedding while receiving pritelivir compared with valacyclovir. Secondary end points included the quantity of HSV in positive swabs and the frequency of genital lesions and shedding episodes. Results Of the 91 randomized participants (median age, 48 years; 57 women [63%]), 56 had completed both treatment periods at the time of the study’s termination. In intent-to-treat analyses, HSV shedding was detected in 2.4% (173 of 7276 ) of swabs during pritelivir treatment compared with 5.3% (392 of 7453) during valacyclovir treatment (relative risk [RR], 0.42; 95% CI, 0.21 to 0.82; P = .01). In swabs with HSV, the mean quantity of HSV was 3.2 log10 copies/mL during pritelivir treatment vs 3.7 log10 copies/mL during valacyclovir treatment (difference, −0.1; 95% CI, −0.6 to 0.5; P = .83). Genital lesions were present on 1.9% of days in the pritelivir group vs 3.9% in the valacyclovir group (RR, 0.40; 95% CI, 0.17-0.96; P = .04). The frequency of shedding episodes did not differ by group, with 1.3 per person-month for pritelivir and 1.6 per person-month for valacyclovir (RR, 0.80; 95% CI, 0.52 to 1.22; P = .29). Treatment-emergent adverse events occurred in 62.3% of participants in the pritelivir group and 69.2% of participants in the valacyclovir group. Conclusions and Relevance Among adults with frequently recurring genital HSV-2, the use of pritelivir compared with valacyclovir resulted in a lower percentage of swabs with HSV detection over 28 days. Further research is needed to assess longer-term efficacy and safety

    Novel non-heteroarylpyrimidine (HAP) capsid assembly modifiers have a different mode of action from HAPs in vitro

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    One of the most promising viral targets in current hepatitis B virus (HBV) drug development is the core protein due to its multiple roles in the viral life cycle. Here we investigated the differences in the mode of action and antiviral activity of representatives of six different capsid assembly modifier (CAM) scaffolds: three from the well-characterized scaffolds heteroarylpyrimidine (HAP), sulfamoylbenzamide (SBA), and phenylpropenamide (PPA), and three from novel scaffolds glyoxamide-pyrrolamide (GPA), pyrazolyl-thiazole (PT), and dibenzo-thiazepin-2-one (DBT). The target activity and antiviral efficacy of the different CAMs were tested in biochemical and cellular assays. Analytical size exclusion chromatography and transmission electron microscopy showed that only the HAP compound induced formation of aberrant non-capsid structures (class II mode of action), while the remaining CAMs did not affect capsid gross morphology (class I mode of action). Intracellular lysates from the HepAD38 cell line, inducibly replicating HBV, showed no reduction in the quantities of intracellular core protein or capsid after treatment with SBA, PPA, GPA, PT, or DBT compounds; however HAP-treatment led to a profound decrease in both. Additionally, immunofluorescence staining of compound-treated HepAD38 cells showed that all non-HAP CAMs led to a shift in the equilibrium of HBV core antigen (HBcAg) towards complete cytoplasmic staining, while the HAP induced accumulation of HBcAg aggregates in the nucleus. Our study demonstrates that the novel scaffolds GPA, PT, and DBT exhibit class I modes of action, alike SBA and PPA, whereas HAP remains the only scaffold belonging to class II inhibitors

    A conceptual governance framework for climate change adaptation and disaster risk reduction integration

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    Climate change adaptation (CCA) and disaster risk reduction (DRR) have similar targets and goals in relation to climate change and related risks. The integration of CCA in core DRR operations is crucial to provide simultaneous benefits for social systems coping with challenges posed by climate extremes and climate change. Although state actors are generally responsible for governing a public issue such as CCA and DRR integration, the reform of top-down governing modes in neoliberal societies has enlarged the range of potential actors to include non state actors from economic and social communities. These new intervening actors require in-depth investigation. To achieve this goal, the article investigates the set of actors and their bridging arrangements that create and shape governance in CCA and DRR integration. The article conducts a comprehensive literature review in order to retrieve main actors and arrangements. The article summarizes actors and arrangements into a conceptual governance framework that can be used as a backdrop for future research on the topic. However, this framework has an explorative form, which must be refined according to site- and context-specific variables, norms, or networks. Accordingly, this article promotes an initial application of the framework to different contexts. Scholars may adopt the framework as a roadmap with which to corroborate the existence of a theoretical and empirical body of knowledge on governance of CCA and DRR integration

    The Science Performance of JWST as Characterized in Commissioning

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    This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

    The James Webb Space Telescope Mission

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    Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4m4m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5m6.5m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure
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