Snakebites and COVID-19: two crises, one research and development opportunity.

Despite inherent differences, Snakebite Envenoming and COVID- 19 have much in common in terms of research and development (R&D) challenges and opportunities. Both crises require a diversified portfolio of R&D solutions, ranging from diagnostics to treatments, that can effectively work and be accessible in different resource settings. Collaborative clinical research and streamlined regulatory pathways are critical to accelerate these candidates in the R&D pipeline. Transformative progress is possible with a concerted approach that aligns strong political will, coordinated financing and the needs of the most marginalised communities

Combining High-Level and Low-Level Approaches to Evaluate Software Implementations Robustness Against Multiple Fault Injection Attacks

International audiencePhysical fault injections break security functionalities of algorithms by targeting their implementations. Software techniques strengthen such implementations to enhance their robustness against fault attacks. Exhaustively testing physical fault injections is time consuming and requires complex platforms. Simulation solutions are developed for this specific purpose. We chose two independent tools presented in 2014, the Laser Attack Robustness (Lazart) and the Embedded Fault Simulator (EFS) in order to evaluate software implementations against multiple fault injection attacks. Lazart and the EFS share the common goal that consists in detecting vulnerabilities in the code. However, they operate with different techniques , fault models and abstraction levels. This paper aims at exhibiting specific advantages of both approaches and proposes a combining scheme that emphasizes their complementary nature

Understanding and tackling snakebite envenoming with transdisciplinary research

Snakebite envenoming (SBE) is a neglected tropical disease (NTD) of high global impact. The World Health Organization (WHO) estimates 4.5 to 5.4 million people are bitten by snakes annually, resulting in 1.8 to 2.7 million envenomings, 81,000 to 138,000 deaths, and at least 400,000 people suffering from physical or psychological sequelae. SBE mostly affects impoverished rural populations in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, thus fueling a vicious cycle of poverty and illness. SBE not only affects humans, but also domestic animals, including livestock, with negative social and economic consequences. This requires a better understanding of the complex social, cultural, and ecological contexts where SBE occurs, within the conceptual frame of One Health, an integrated approach that recognizes the health of humans, animals, and the environment as closely linked and interdependent. Such complexity demands more integrative approaches for better understanding and confronting this disease. SBE has unique features that make its prevention and control challenging. Unlike many infectious diseases, SBE cannot be eradicated, but its incidence and impact can be reduced through effective programs aimed at better prevention and rapid access to treatment. This in turn demands the engagement of communities to improve the cohabitation of humans, domestic animals, and snakes in rural agroecosystems. In 2019, the WHO launched a strategy for the prevention and control of SBE, aimed at halving the deaths and disabilities caused by this NTD by the year 2030. This strategy is based on 4 pillars, i.e., empower and engage communities; ensure safe, effective treatment; strengthen health systems; and increase partnerships, coordination, and resources. Building on previous ideas and publications, this article discusses and advocates for transdisciplinary research on SBE and for promoting dialogue and collaboration between sectors, particularly by engaging communities affected by SBE at all levels of the research process

Liability in Software Engineering: Overview of the LISE Approach and Illustration on a Case Study

© ACM – 2010. This is the authors' pre-version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version was published in the Proceedings of the 32nd ACM/IEEE international Conference on Software Engineering (ICSE'10) - Volume 1 – 978-1-60558-719-6/10/05 – (May 2-8 – 2010) http://doi.acm.org/10.1145/1806799.1806823LISE is a multidisciplinary project involving lawyers and computer scientists with the aim to put forward a set of methods and tools to (1) define software liability in a precise and unambiguous way and (2) establish such liability in case of incident. This report provides an overview of the overall approach taken in the project based on a case study. The case study illustrates a situation where, in order to reduce legal uncertainties, the parties to a contract wish to include in the agreement specific clauses to define as precisely as possible the share of liabilities between them for the main types of failures of the system

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial.

BackgroundSnakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa.Methodology/principal findingsOur market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness.Conclusions/significanceClinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms

Recommendations for addressing VL in Somalia.

<p>Recommendations for addressing VL in Somalia.</p

Treatment options for second-stage gambiense human African trypanosomiasis

Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients’ access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program