226 research outputs found

    Estimated effects of climate change on flood vulnerability of U.S. bridges

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    We assessed the potential impacts of increased river flooding from climate change on bridges in the continental United States. Daily precipitation statistics from four climate models and three greenhouse gas (GHG) emissions scenarios (A2, A1B, and B1) were used to capture a range of potential changes in climate. Using changes in maximum daily precipitation, we estimated changes to the peak flow rates for the 100-year return period for 2,097 watersheds. These estimates were then combined with information from the National Bridge Inventory database to estimate changes to bridge scour vulnerability. The results indicate that there may be significant potential risks to bridges in the United States from increased precipitation intensities. Approximately 129,000 bridges were found to be currently deficient. Tens of thousands to more than 100,000 bridges could be vulnerable to increased river flows. Results by region vary considerably. In general, more bridges in eastern areas are vulnerable than those in western areas. The highest GHG emissions scenarios result in the largest number of bridges being at risk. The costs of adapting vulnerable bridges to avoid increased damage associated with climate change vary from approximately 140to140 to 250 billion through the 21st century. If these costs were spread out evenly over the century, the annual costs would be several billion dollars. The costs of protecting the bridges against climate change risks could be reduced by approximately 30% if existing deficient bridges are improved with riprap.United States. Environmental Protection Agency. Office of Atmospheric Programs (Contract #EP-W-07-072

    A dual role for A-type lamins in DNA double-strand break repair

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    A-type lamins are emerging as regulators of nuclear organization and function. Changes in their expression are associated with cancer and mutations are linked to degenerative diseases—laminopathies. Although a correlation exists between alterations in lamins and genomic instability, the molecular mechanisms remain largely unknown. We previously found that loss of A-type lamins leads to degradation of 53BP1 protein and defective long-range non-homologous end-joining (NHEJ) of dysfunctional telomeres. Here, we determined how loss of A-type lamins affects the repair of short-range DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). We find that lamins deficiency allows activation of the DNA damage response, but compromises the accumulation of 53BP1 at IR-induced foci (IRIF), hindering the fast phase of repair corresponding to classical-NHEJ. Importantly, reconstitution of 53BP1 is sufficient to rescue long-range and short-range NHEJ. Moreover, we demonstrate an unprecedented role for A-type lamins in the maintenance of homologous recombination (HR). Depletion of lamins compromises HR by a mechanism involving transcriptional downregulation of BRCA1 and RAD51 by the repressor complex formed by the Rb family member p130 and E2F4. In line with the DNA repair defects, lamins-deficient cells exhibit increased radiosensitivity. This study demonstrates that A-type lamins promote genomic stability by maintaining the levels of proteins with key roles in DNA DSBs repair by NHEJ and HR. Our results suggest that silencing of A-type lamins by DNA methylation in some cancers could contribute to the genomic instability that drives malignancy. In addition, lamins-deficient tumor cells could represent a good target for radiation therapy

    Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

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    Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

    Re-thinking Secularism in Post-Independence Tunisia

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    The victory of a Tunisian Islamist party in the elections of October 2011 seems a paradox for a country long considered the most secular in the Arab world and raises questions about the nature and limited reach of secularist policies imposed by the state since independence. Drawing on a definition of secularism as a process of defining, managing, and intervening in religious life by the state, this paper identifies how under Habib Bourguiba and Zine al-Abidine Ben Ali the state sought to subordinate religion and to claim the sole right to interpret Islam for the public in an effort to win the monopoly over religious symbolism and, with it, political control. Both Bourguiba and Ben Ali relied on Islamic references for legitimacy, though this recourse to religion evolved to face changing contexts, and both sought to define Islam on their own terms. Bourguiba sought to place himself personally at the summit of power, while under Ben Ali the regime forged an authoritarian consensus of security, unity, and ‘tolerance’. In both cases the state politicised Islam but failed to maintain a monopoly over religious symbolism, facing repeated religious challenges to its political authority

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Challenging National Narratives: On the Origins of Sweet Potato in China as Global Commodity During the Early Modern Period

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    The introduction of American cereal crops is probably one of the most important events in China¿s agricultural history, having a great effect on the agriculture production, national life, the transformation of consumer behaviour and, to some extent, the nationalization of consumption. The sweet potato (Ipomoea Batatas L.), in Chinese g¿nsh¿ ¿¿, is a staple food crop for ancient Chinese society. Today it still plays an important role in Chinese daily life, as well as guaranteeing national food security.GECEM Project, Global Encounters between China and Europe: Trade Networks, Consumption and Cultural Exchanges in Macau and Marseille (1680-1840), ERC (European Research Council)- Starting Grant, programa Horizon 2020, número de ref. 679371, www.gecem.eu.Versión del edito

    Male breast cancer in BRCA1 and BRCA2 mutation carriers : pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

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    Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Peer reviewe

    Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

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    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352
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