Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

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

Consistent Inconsistency Management: A Concern-Driven Approach

During the development of a software system, architects deal with a large number of stakeholders, each with differing concerns. This inevitably leads to inconsistency: goals, concerns, design decisions, and models are interrelated and overlapping. Existing approaches to support inconsistency management are limited in their applicability and usefulness in day to day practice due to the presence of incomplete, informal and heterogeneous models in software architecture. This paper presents a novel process in the form of a lightweight generic method, the Concern-Driven Inconsistency Management (CDIM) method, that is designed to address limitations of different related approaches. It aims to aid architects with management of intangible inconsistency in software architecture

An evolutionary game theoretical model shows the limitations of the additive partitioning method for interpreting biodiversity experiments

1.The relationship between diversity and ecosystem functioning is often analysed by partitioning the change in species performance in mixtures into a complementarity effect (CE) and a selection effect (SE). There is continuing ambiguity in the literature on the interpretation of these effects, mainly in their relationship to ecological mechanisms and processes. 2.Here, we present the emergence of complementarity and selection effects in the results of an evolutionary game theoretical model for plant competition which is exclusively based on competition for light. Eight plant strategies, differing only in the time of onset of flowering, were played against one another to determine the relationship between plant trait differences and CE vs. SE. 3.We show that competitive exclusion may occur even in the presence of a positive CE, i.e. when CE > 0. CE was highest at intermediate differences in flowering time. Increasing trait differences may, therefore, increase CE without leading to coexistence. 4.SE was strongly dependent on which of the strategies was paired. SE was mostly positive if one of the players was early flowering (with low seed yield) and the other strategy had higher monoculture yields. SE was mostly negative if one of the players was late flowering, leading to low monoculture yield for this strategy, but to high gains when competing with strategies that produce less leaf area. The average SE was negative over all pairs. 5.Synthesis. These results show that CE may be positive if the species interaction is beneficial for only one of the two competitors, and the sign of SE depends critically on the underlying mechanism for performance in monoculture. Positive complementarity may go hand in hand with competitive exclusion, while widely different outcomes in SE are possible within a single mechanistic background. Consequently, the way SE changes with increasing richness are not only related to a sampling/selection effect but also by the way the interacting species affect the competitive environment. Interpreting the additive partitioning method with a set notion in mind about the driving mechanisms could lead to incorrect conclusions on how species richness effects drive ecosystem functioning

Plant species richness leaves a legacy of enhanced root litter-induced decomposition in soil

Increasing plant species richness generally enhances plant biomass production, which may enhance accumulation of carbon (C) in soil. However, the net change in soil C also depends on the effect of plant diversity on C loss through decomposition of organic matter. Plant diversity can affect organic matter decomposition via changes in litter species diversity and composition, and via alteration of abiotic and/or biotic attributes of the soil (soil legacy effect). Previous studies examined the two effects on decomposition rates separately, and do therefore not elucidate the relative importance of the two effects, and their potential interaction. Here we separated the effects of litter mixing and litter identity from the soil legacy effect by conducting a factorial laboratory experiment where two fresh single root litters and their mixture were mixed with soils previously cultivated with single plant species or mixtures of two or four species. We found no evidence for litter-mixing effects. In contrast, root litter-induced CO2 production was greater in soils from high diversity plots than in soils from monocultures, regardless of the type of root litter added. Soil microbial PLFA biomass and composition at the onset of the experiment was unaffected by plant species richness, whereas soil potential nitrogen (N) mineralization rate increased with plant species richness. Our results indicate that the soil legacy effect may be explained by changes in soil N availability. There was no effect of plant species richness on decomposition of a recalcitrant substrate (compost). This suggests that the soil legacy effect predominantly acted on the decomposition of labile organic matter. We thus demonstrated that plant species richness enhances root litter-induced soil respiration via a soil legacy effect but not via a litter-mixing effect. This implies that the positive impacts of species richness on soil C sequestration may be weakened by accelerated organic matter decomposition

Mind the blind spot: lessons from fungal community sequencing in a plant–soil feedback experiment

Abstract Background Plant–soil feedback (PSF) has gained increasing interest in agricultural systems. An important question is whether PSF differs between different cropping systems. Few attempts have yet been made to identify the pathogen species involved in negative PSF. Here, we hypothesize that the strength of negative PSF experienced by a crop species is determined by the relative abundance of host-specific soil-borne pathogenic fungi, that is in turn driven by the crop’s relative abundance (in time). Methods We performed a PSF experiment, with different soils originating from three cropping systems in the North China Plain and three crop species (wheat, maize, soybean) in a full factorial design. Soil fungal community composition and relative abundance of fungal (pathogen) species in each treatment was identified by metabarcoding using ITS (Internal Transcribed Spacer) sequencing. Results PSF ranged from negative for wheat, neutral to negative for soybean and neutral to positive for maize, but the former density of a crop in a particular cropping system did not affect the strength of PSF experienced by each of the three. No relationships between fungal pathogen abundance and PSF were found, but we did find a surprisingly large enrichment across steps of the experiment of Chaetomium spp., a known cellulose-degrading fungus. This may be explained by addition of filter paper on the bottom of the pots. Conclusions Our results suggest that the strength of PSF in these crops is not related to the relative abundance of specific fungal pathogens. However, we cannot rule out that our results were affected by the high abundance of one particular cellulose-degrading fungus. This highlights both the need to stop the practice of using filter paper in pot experiments, as well as the relevance of assessing the identity, relative abundance and potential functions of fungal taxa in PSF experiments