Second-generation PLINK: rising to the challenge of larger and richer datasets

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.Comment: 2 figures, 1 additional fil

High-order discrete ordinate transport in hexagonal geometry: A new capability in ERANOS

This paper presents the implementation of an arbitrary order discontinuous Galerkin scheme within the framework of a discrete ordinate solver of the neutron transport equation for nuclear reactor calculations. More precisely, it deals with non-conforming spatial meshes for the 2D and 3D modeling of core geometries based on hexagonal assemblies. This work aims at improving the capabilities of the ERANOS code system dedicated to fast reactor analysis and design. Both the angular quadrature and spatial scheme peculiarities for hexagonal geometries are presented. A particular focus is set on the spatial non-conforming mesh and variable order capabilities of this scheme in anticipation to the development of spatial adaptiveness algorithms. These features are illustrated on a 3D numerical benchmark with comparison to a Monte Carlo reference and a 2D benchmark that shows the potential of this scheme for both h- and p-adaptation

Hydrological impacts of climate change on the Tejo and Guadiana Rivers

International audienceA distributed daily rainfall?runoff model is applied to the Tejo and Guadiana river basins in Spain and Portugal to simulate the effects of climate change on runoff production, river flows and water resource availability with results aggregated to the monthly level. The model is calibrated, validated and then used for a series of climate change impact assessments for the period 2070?2100. Future scenarios are derived from the HadRM3H regional climate model (RCM) using two techniques: firstly a bias-corrected RCM output, with monthly mean correction factors calculated from observed rainfall records; and, secondly, a circulation-pattern-based stochastic rainfall model. Major reductions in rainfall and streamflow are projected throughout the year; these results differ from those for previous studies where winter increases are projected. Despite uncertainties in the representation of heavily managed river systems, the projected impacts are serious and pose major threats to the maintenance of bipartite water treaties between Spain and Portugal and the supply of water to urban and rural regions of Portugal

Non-communicable diseases in emergencies: a call to action

Recent years have demonstrated the devastating health consequences of complex emergencies and natural disasters and thereby highlighted the importance of comprehensive and collaborative approaches to humanitarian responses and risk reduction. Simultaneously, noncommunicable diseases are now recognised as a real and growing threat to population health and development; a threat that is magnified by and during emergencies. Noncommunicable diseases, however, continue to receive little attention from humanitarian organisations in the acute phase of disaster and emergency response. This paper calls on all sectors to recognise and address the specific health challenges posed by noncommunicable diseases in emergencies and disaster situations. This publication aims to highlight the need for: • Increased research on morbidity and mortality patterns due to noncommunicable diseases during and following emergencies; • Raised awareness through greater advocacy for the issue and challenges of noncommunicable diseases during and following emergencies; • Incorporation of noncommunicable diseases into existing emergency-related policies, standards, and resources; • Development of technical guidelines on the clinical management of noncommunicable diseases in emergencies; • Greater integration and coordination in health service provision during and following emergencies; • Integrating noncommunicable diseases into practical and academic training of emergency workers and emergency-response coordinators

Retours d'expériences et perspectives d'utilisation de la méthode "Imagine". Analyse systémique et prospective de durabilité -

La montée en puissance des préoccupations environnementales se traduit par des demandes sociale et politique en faveur de la participation du public à la conception et la mise en uvre de stratégies territoriales de long terme. Dans ce contexte, le Plan Bleu a développé, expérimenté et consolidé une méthode d'analyse systémique et prospective territoriale, "Imagine", qui propose des outils pour décrire, évaluer et explorer le niveau de durabilité d'un éco-socio-système, à travers une approche participative considérant les acteurs locaux comme experts de leur territoire

Feedback and potential uses of the "Imagine" method : A systemic and predictive analysis of sustainability -

Preoccupation with the environment has gained increasing prominence, reflected in social and political demands for general public participation in the conception ad implementation of long-term strategy for defined geographical or administrative areas. In this context, the Blue Plan has developed, tested and consolidated a method of systemic, predictive and proactive analysis "Imagine", that proposes tools for describing, evaluating and investigating the degree of sustainability of a socio-ecosystem. It is based on a participatory approach that considers local stakeholders and others involved as experts in their area

Thermoresponsive worms for expansion and release of human embryonic stem cells

The development of robust suspension cultures of human embryonic stem cells (hESCs) without the use of cell membrane disrupting enzymes or inhibitors is critical for future clinical applications in regenerative medicine. We have achieved this by using long, flexible, and thermoresponsive polymer worms decorated with a recombinant vitronectin subdomain that bridge hESCs, aiding in hESC's natural ability to form embryoid bodies (EBs) and satisfying their inherent requirement for cell-cell and cell-extracellular matrix contact. When the EBs reached an optimal upper size where cytokine and nutrient penetration becomes limiting, these long and flexible polymer worms facilitated EB breakdown via a temperature shift from 37 to 25 C. The thermoresponsive nature of the worms enabled a cyclical dissociation and propagation of the cells. Repeating the process for three cycles (over eighteen days) provided a >30-fold expansion in cell number while maintaining pluripotency, thereby providing a simple, nondestructive process for the 3D expansion of hESC