Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Etude comparative de différentes méthodes pour évaluer les pressions moyennes d'une zone de distribution d'eau potable

International audienceThe leakage rate in water distribution pipelines is dependent on service pressure. Real water losses can be evaluated at network level (annual indicator) or DMA level (in the case of networks divided into sectors). To establish a link between pressure and real losses, pressure must be estimated at these same scales. Pressure is a parameter that varies in both space (notably, as a function of altitude) and time (notably for variations in head loss which are linked to flows). Therefore, it is necessary to define the notion of zonal pressures and to determine the way that they can be evaluated. To evaluate pressure for a zone or network, the IWA developed the concepts of Current Average System Pressure (CASP) and Average Zone Night Pressure (AZNP). The Water Services Association of Australia (WSAA) has produced its own guide to estimating average pressure in distribution systems and zones (WSAA, 2009). The methodology used in this guide is designed for sectorised networks, and makes systematic use of AZPs (Average Zone Points). Because of this, it is not suitable for use in all contexts, especially in France. In view of this, and as part of a study conducted for the Office National de l’Eau et des Milieux Aquatiques (ONEMA), Irstea examined a number of variants of this approach, some of which can be used without the need for AZPs, as well as in networks with no DMAs. Two networks containing four and seven DMAs respectively were analysed. Three methods for calculating the mean zonal pressure were used: "Topographic", "Hydraulic model", and "Measurement". All three methods are broadly suited to most networks, each coming with its own advantages and disadvantages. On this basis, no method should be entirely discounted. The study highlighted that the weighting system has a strong impact on results. It is therefore recommended to use a weighting method that is, as much as possible, linked to the causes of leaks (e.g. "number of service connections" or "daily demand"). For simple and reliable use of the "hydraulic model" method, two tools based on the EPAnet application were developed. The first makes it possible to connect each pipe and node from the model to a given DMA, and the second allows pressure indicators to be calculated for each DMA as well as the network as a whole

Rethinking the Emergence of Relationship Marketing

In this article, the history of relationship marketing (RM) is challenged. Similar to discussions of the marketing concept, the debates surrounding RM are largely ahistorical. This is despite numerous scholars indicating that RM has a far longer history than is currently appreciated. In contrast to received wisdom that RM emerged in the late 1970s, it is demonstrated that RM themes have been present in the marketing literature for longer than is recognized by the contemporary scholars

On the Verge of a Grand Solar Minimum: A Second Maunder Minimum?

We analyze the yearly mean sunspot-number data covering the period 1700 to 2012. We show that the yearly sunspot number is a low-dimensional deterministic chaotic system. We perform future predictions trying to forecast the solar activity during the next five years (2013 -aEuro parts per thousand 2017). We provide evidence that the yearly sunspot-number data can be used for long-term predictions. To test and prove that our model is able to predict the Maunder Minimum period (1645 -aEuro parts per thousand 1715), we perform long-term post-facto predictions comparing them with the observed sunspot-number values. We also perform long-term future predictions trying to forecast the solar activity up to 2102. Our predictions indicate that the present Cycle 24 is expected to be a low-peak cycle. We conclude that the level of solar activity is likely to be reduced significantly during the next 90 years, somewhat resembling the Maunder Minimum period