An integrated socio-environmental framework for mapping hazard-specific vulnerability and exposure in urban areas

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordHazards act upon vulnerability and exposure to create disaster risk. Despite the growth of disaster risk assessments, the number of approaches that develop vulnerability and exposure studies is still small when compared with hazard modelling. In fact, limited studies have considered the relationship between vulnerability and exposure variables and how this can change future management actions on a local scale. This paper addresses this gap by proposing an integrated framework with a combination of social and environmental sciences to map hazard-specific vulnerability and exposure in urban areas. Subjective (e.g. Participatory Approach) and objective methods (e.g. Shannon Entropy and Fuzzy Theory) were integrated into a pixel-by-pixel framework for enhancing the flooding management in Campina Grande, Brazil. The results express the spatial distribution of flood vulnerability and exposure and assess key issues for flood management in different vulnerability categories. Challenges for the integration of socio-environmental approaches in water resources studies are discussed

Understanding the NEEDS for ACTING: An integrated framework for applying nature-based solutions in Brazil

This is the final version. Available on open access from IWA Publishing via the DOI in this recordData availability statement: Data cannot be made publicly available; readers should contact the corresponding author for details.Nature-based solutions (NBS) support the provision of multiple benefits for the environment and society. First idealised in 2008, NBS are recommended by worldwide reports and guidelines as strategies to protect, sustainably manage and restore ecosystems. However, their operationalisation is still in the early stages, especially in developing countries, and only a few studies consider their full potential. This article contributes to this context by developing an integrated framework, with spatial and participatory tools, for analysing flood risk mitigation in Brazil. The approach enables a deep understanding of the societal challenges and vulnerabilities of the area (i.e., NEEDS) for subsequently planning the appropriate NBS (i.e., ACTIONS), with the participation of 255 stakeholders of Campina Grande municipality. Results show mappings of flood-prone areas, in which approximately 52% of the flooded areas will see an increase in the future. Hotspots (i.e., hazard, vulnerability, and exposure) are shown and discussed with four application cases. Finally, multiple benefits of seven NBS alternatives are analysed in 53 scenarios of application, in which the higher rates of reductions are found to combined alternatives. The discussion emphasizes the importance of spatially assessing the 'needs' and 'multiple benefits' of NBS, including reducing vulnerabilities and increment of resilience.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (Capes)European Union Horizon 202

Addressing social and institutional vulnerabilities in the context of flood risk mitigation

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.There are different perspectives of what constitutes disaster risk. Among the “hazards”-tradition research, more focus is given to modelling hazards, and less effort is made to understand the vulnerabilities. Considering vulnerabilities as the inherent characteristics of the place that create the potential to harm, this paper highlights the importance of understanding the vulnerabilities of the place before defining actions for flood risk mitigation (FRM). In this sense, a participatory approach, the Project PLANEJEEE, was developed to understand the social and institutional vulnerabilities of FRM in Campina Grande, Brazil. Data was collected with the collaboration with 199 stakeholders through surveys, workshop and focus groups. The results reflect the analysis of risk perception and coping capacity of communities at risk (n = 172), and the institutional context with the involvement with policymakers and local specialists (n = 27). Although results confirm that individuals faced severe flood risk cases previously, they still need resources for increasing their coping capacity and their own risk protection. Institutional vulnerabilities are shown with the contrast between challenges and actions for FRM. Findings show that multiple challenges in social and institutional contexts should be systematically addressed to propose actions to reduce flood risk vulnerability, and increase resilience.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES)European Commissio

H-Ferritin Is Essential for Macrophages' Capacity to Store or Detoxify Exogenously Added Iron

Macrophages are central cells both in the immune response and in iron homeostasis. Iron is both essential and potentially toxic. Therefore, iron acquisition, transport, storage, and release are tightly regulated, by several important proteins. Cytosolic ferritin is an iron storage protein composed of 24 subunits of either the L- or the H-type chains. H-ferritin differs from L-ferritin in the capacity to oxidize Fe2+ to Fe3+. In this work, we investigated the role played by H-ferritin in the macrophages' ability to respond to immune stimuli and to deal with exogenously added iron. We used mice with a conditional deletion of the H-ferritin gene in the myeloid lineage to obtain bone marrow-derived macrophages. These macrophages had normal viability and gene expression under basal culture conditions. However, when treated with interferon-gamma and lipopolysaccharide they had a lower activation of Nitric Oxide Synthase 2. Furthermore, H-ferritin-deficient macrophages had a higher sensitivity to iron-induced toxicity. This sensitivity was associated with a lower intracellular iron accumulation but a higher production of reactive oxygen species. These data indicate that H-ferritin modulates macrophage response to immune stimuli and that it plays an essential role in protection against iron-induced oxidative stress and cell death.Tis work was fnanced by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/IMI-MIC/1683/2014 (POCI-01-0145-FEDER-016590). PFO and MGA acknowledge FCT for the Investigador FCT 2015. We thank the valuable collaboration of the following i3S Scientifc Platforms: Cell Culture and Genotyping Core Facility (CCGen), [Histology and Electron Microscopy Service (HEMS), and BioSciences Screening], member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)], Animal Facility, and Flow Cytometry Unit (TraCy). We acknowledge Lukas Kuhn (Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland) for kindly providing the frst breeding pairs of Fth1−/− mice. Te authors also acknowledge Marisa Castro, from Departamento de Biologia Molecular from ICBAS, Clara Bento, from i3S, and Edgar Pinto from LAQV – REQUIMTE for technical assistance at diferent stages of the project

RAId_aPS: MS/MS analysis with multiple scoring functions and spectrum-specific statistics

Statistically meaningful comparison/combination of peptide identification results from various search methods is impeded by the lack of a universal statistical standard. Providing an E-value calibration protocol, we demonstrated earlier the feasibility of translating either the score or heuristic E-value reported by any method into the textbook-defined E-value, which may serve as the universal statistical standard. This protocol, although robust, may lose spectrum-specific statistics and might require a new calibration when changes in experimental setup occur. To mitigate these issues, we developed a new MS/MS search tool, RAId_aPS, that is able to provide spectrum-specific E-values for additive scoring functions. Given a selection of scoring functions out of RAId score, K-score, Hyperscore and XCorr, RAId_aPS generates the corresponding score histograms of all possible peptides using dynamic programming. Using these score histograms to assign E-values enables a calibration-free protocol for accurate significance assignment for each scoring function. RAId_aPS features four different modes: (i) compute the total number of possible peptides for a given molecular mass range, (ii) generate the score histogram given a MS/MS spectrum and a scoring function, (iii) reassign E-values for a list of candidate peptides given a MS/MS spectrum and the scoring functions chosen, and (iv) perform database searches using selected scoring functions. In modes (iii) and (iv), RAId_aPS is also capable of combining results from different scoring functions using spectrum-specific statistics. The web link is http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/raid_aps/index.html. Relevant binaries for Linux, Windows, and Mac OS X are available from the same page.Comment: 34 pages, 10 figures, 1 supplementary information file (RAId_aPS_support.pdf). To view the supplementary file, please download and extract the gzipped tar source file listed under "Other formats

Place-Based Citizen Science for Assessing Risk Perception and Coping Capacity of Households Affected by Multiple Hazards

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical constraints.Since hazards act upon vulnerability and exposure to become disasters, the understanding of societal challenges is key for disaster risk reduction. This condition is even more critical when more than one hazard is in place. Taking the case of flooding and water shortage, this study is built upon the premise that disasters are a social phenomenon; therefore, it is essential to comprehend the social context in which they occur. Particularly, this study aims to evaluate the similarities and differences in risk perception and the coping capacity of residents in the multiple-hazard context. For this, a place-based citizen science approach was developed in this study in Campina Grande, a semiarid region of Brazil, with the collaboration of 199 participants. Risk perception and coping capacity were analysed through the citizens’ participation, while combining subjective and objective methods. The results indicate that even though residents have experienced severe flooding and water shortages in the past, they still have low coping capacity. The findings highlight the need to combine a triad of societal challenges, namely information, trust, and incentives, to improve coping capacity in the future and increase resilience. This study underlines the need to understand multiple hazards according to social, spatial, and temporal scales in a socio-spatial perspective

Magnetic Fluffy Dark Matter

We explore extensions of inelastic Dark Matter and Magnetic inelastic Dark Matter where the WIMP can scatter to a tower of heavier states. We assume a WIMP mass $m_\chi \sim \mathcal{O}(1-100)$ GeV and a constant splitting between successive states $\delta \sim\mathcal{O}(1 - 100)$ keV. For the spin-independent scattering scenario we find that the direct experiments CDMS and XENON strongly constrain most of the DAMA/LIBRA preferred parameter space, while for WIMPs that interact with nuclei via their magnetic moment a region of parameter space corresponding to $m_{\chi}\sim 11$ GeV and $\delta < 15$ keV is allowed by all the present direct detection constraints.Comment: 16 pages, 6 figures, added comments about magnetic moment form factor to Sec 3.1.2 and results to Sec 3.2.2, final version to be published in JHE

Slepton mass-splittings as a signal of LFV at the LHC

Precise measurements of slepton mass-splittings might represent a powerful tool to probe supersymmetric (SUSY) lepton flavour violation (LFV) at the LHC. We point out that mass-splittings of the first two generations of sleptons are especially sensitive to LFV effects involving $\tau-\mu$ transitions. If these mass-splittings are LFV induced, high-energy LFV processes like the neutralino decay {\nt}_2\to\nt_1\tau^{\pm}\mu^{\mp} as well as low-energy LFV processes like $\tau\to\mu\gamma$ are unavoidable. We show that precise slepton mass-splitting measurements and LFV processes both at the high- and low-energy scales are highly complementary in the attempt to (partially) reconstruct the flavour sector of the SUSY model at work. The present study represents another proof of the synergy and interplay existing between the LHC, i.e. the {\em high-energy frontier}, and high-precision low-energy experiments, i.e. the {\em high-intensity frontier}.Comment: 11 pages, 5 figures. v2: added discussion on backgrounds, added references, version to be published on JHE

Strategies to reduce sample sizes in Alzheimer’s disease primary and secondary prevention trials using longitudinal amyloid PET imaging

BACKGROUND: Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer's disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could improve statistical power in AD prevention trials. METHODS: Baseline and annualized % change in [11C]PIB SUVR and DVR were computed for a global (cortical) and regional (early) composite from scans of 237 cognitively unimpaired subjects from the OASIS-3 database ( www.oasis-brains.org ). Bland-Altman and correlation analyses were used to assess the relationship between SUVR and DVR. General linear models and linear mixed effects models were used to determine effects of age, sex, and APOE-ε4 carriership on baseline and longitudinal amyloid burden. Finally, differences in statistical power of SUVR and DVR (cortical or early composite) were assessed considering three anti-amyloid trial scenarios: secondary prevention trials including subjects with (1) intermediate-to-high (Centiloid > 20.1), or (2) intermediate (20.1 < Centiloid ≤ 49.4) amyloid burden, and (3) a primary prevention trial focusing on subjects with low amyloid burden (Centiloid ≤ 20.1). Trial scenarios were set to detect 20% reduction in accumulation rates across the whole population and in APOE-ε4 carriers only. RESULTS: Although highly correlated to DVR (ρ = .96), cortical SUVR overestimated DVR cross-sectionally and in annual % change. In secondary prevention trials, DVR required 143 subjects per arm, compared with 176 for SUVR. Both restricting inclusion to individuals with intermediate amyloid burden levels or to APOE-ε4 carriers alone further reduced sample sizes. For primary prevention, SUVR required less subjects per arm (n = 855) compared with DVR (n = 1508) and the early composite also provided considerable sample size reductions (n = 855 to n = 509 for SUVR, n = 1508 to n = 734 for DVR). CONCLUSION: Sample sizes in AD secondary prevention trials can be reduced by the acquisition of dynamic PET scans and/or by restricting inclusion to subjects with intermediate amyloid burden or to APOE-ε4 carriers only. Using a targeted early composite only leads to reductions of sample size requirements in primary prevention trials. These findings support strategies to enable smaller Proof-of-Concept Phase II clinical trials to better streamline drug development

Strategies to reduce sample sizes in Alzheimer’s disease primary and secondary prevention trials using longitudinal amyloid PET imaging

BACKGROUND: Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer's disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could improve statistical power in AD prevention trials. METHODS: Baseline and annualized % change in [11C]PIB SUVR and DVR were computed for a global (cortical) and regional (early) composite from scans of 237 cognitively unimpaired subjects from the OASIS-3 database ( www.oasis-brains.org ). Bland-Altman and correlation analyses were used to assess the relationship between SUVR and DVR. General linear models and linear mixed effects models were used to determine effects of age, sex, and APOE-ε4 carriership on baseline and longitudinal amyloid burden. Finally, differences in statistical power of SUVR and DVR (cortical or early composite) were assessed considering three anti-amyloid trial scenarios: secondary prevention trials including subjects with (1) intermediate-to-high (Centiloid > 20.1), or (2) intermediate (20.1 < Centiloid ≤ 49.4) amyloid burden, and (3) a primary prevention trial focusing on subjects with low amyloid burden (Centiloid ≤ 20.1). Trial scenarios were set to detect 20% reduction in accumulation rates across the whole population and in APOE-ε4 carriers only. RESULTS: Although highly correlated to DVR (ρ = .96), cortical SUVR overestimated DVR cross-sectionally and in annual % change. In secondary prevention trials, DVR required 143 subjects per arm, compared with 176 for SUVR. Both restricting inclusion to individuals with intermediate amyloid burden levels or to APOE-ε4 carriers alone further reduced sample sizes. For primary prevention, SUVR required less subjects per arm (n = 855) compared with DVR (n = 1508) and the early composite also provided considerable sample size reductions (n = 855 to n = 509 for SUVR, n = 1508 to n = 734 for DVR). CONCLUSION: Sample sizes in AD secondary prevention trials can be reduced by the acquisition of dynamic PET scans and/or by restricting inclusion to subjects with intermediate amyloid burden or to APOE-ε4 carriers only. Using a targeted early composite only leads to reductions of sample size requirements in primary prevention trials. These findings support strategies to enable smaller Proof-of-Concept Phase II clinical trials to better streamline drug development