Showing papers by "Université libre de Bruxelles published in 2010"

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

International network of cancer genome projects

Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Association of trypanolytic ApoL1 variants with kidney disease in African Americans.

Abstract: African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

Comparison of Dopamine and Norepinephrine in the Treatment of Shock

Abstract: BACKGROUND Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 μg per kilogram of body weight per minute for dopamine or a dose of 0.19 μg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P = 0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P = 0.03 for cardiogenic shock, P = 0.19 for septic shock, and P = 0.84 for hypovolemic shock, in Kaplan–Meier analyses). CONCLUSIONS Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)

Random numbers certified by Bell's theorem.

Abstract: True randomness does not exist in classical physics, where randomness is necessarily a result of forces that may be unknown but exist. The quantum world, however, is intrinsically truly random. This is difficult to prove, as it is not readily distinguishable from noise and other uncontrollable factors. Now Pironio et al. present proof of a quantitative relationship between two fundamental concepts of quantum mechanics — randomness and the non-locality of entangled particles. They first show theoretically that the violation of a Bell inequality certifies the generation of new randomness, independently of any implementation details. To illustrate the approach, they then perform an experiment in which — as confirmed using the theoretical tools that they developed — 42 new random bits have been generated. As well as having conceptual implications, this work has practical implications for cryptography and for numerical simulation of physical and biological systems. Here it is shown, both theoretically and experimentally, that non-local correlations between entangled quantum particles can be used for a new cryptographic application — the generation of certified private random numbers — that is impossible to achieve classically. The results have implications for future device-independent quantum information experiments and for addressing fundamental issues regarding the randomness of quantum theory. Randomness is a fundamental feature of nature and a valuable resource for applications ranging from cryptography and gambling to numerical simulation of physical and biological systems. Random numbers, however, are difficult to characterize mathematically1, and their generation must rely on an unpredictable physical process2,3,4,5,6. Inaccuracies in the theoretical modelling of such processes or failures of the devices, possibly due to adversarial attacks, limit the reliability of random number generators in ways that are difficult to control and detect. Here, inspired by earlier work on non-locality-based7,8,9 and device-independent10,11,12,13,14 quantum information processing, we show that the non-local correlations of entangled quantum particles can be used to certify the presence of genuine randomness. It is thereby possible to design a cryptographically secure random number generator that does not require any assumption about the internal working of the device. Such a strong form of randomness generation is impossible classically and possible in quantum systems only if certified by a Bell inequality violation15. We carry out a proof-of-concept demonstration of this proposal in a system of two entangled atoms separated by approximately one metre. The observed Bell inequality violation, featuring near perfect detection efficiency, guarantees that 42 new random numbers are generated with 99 per cent confidence. Our results lay the groundwork for future device-independent quantum information experiments and for addressing fundamental issues raised by the intrinsic randomness of quantum theory.

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

Abstract: Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

Sepsis biomarkers: a review

Abstract: Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. The search retrieved 3370 references covering 178 different biomarkers. Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.

How Learning to Read Changes the Cortical Networks for Vision and Language

Abstract: Does literacy improve brain function? Does it also entail losses? Using functional magnetic resonance imaging, we measured brain responses to spoken and written language, visual faces, houses, tools, and checkers in adults of variable literacy (10 were illiterate, 22 became literate as adults, and 31 were literate in childhood). As literacy enhanced the left fusiform activation evoked by writing, it induced a small competition with faces at this location, but also broadly enhanced visual responses in fusiform and occipital cortex, extending to area V1. Literacy also enhanced phonological activation to speech in the planum temporale and afforded a top-down activation of orthography from spoken inputs. Most changes occurred even when literacy was acquired in adulthood, emphasizing that both childhood and adult education can profoundly refine cortical organization.

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

Abstract: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group.

The Microarray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models

Abstract: Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

Management of bleeding following major trauma: an updated European guideline

Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Observation of long-range, near-side angular correlations in proton-proton collisions at the LHC

Abstract: This is the pre-print version of the Published Article, which can be accessed from the link below - Copyright @ 2010 Springer Verlag

Ant Colony Optimization: Overview and Recent Advances

Abstract: Ant Colony Optimization (ACO) is a metaheuristic that is inspired by the pheromone trail laying and following behavior of some ant species. Artificial ants in ACO are stochastic solution construction procedures that build candidate solutions for the problem instance under concern by exploiting (artificial) pheromone information that is adapted based on the ants’ search experience and possibly available heuristic information. Since the proposal of the Ant System, the first ACO algorithm, many significant research results have been obtained. These contributions focused on the development of high-performing algorithmic variants, the development of a generic algorithmic framework for ACO algorithms, successful applications of ACO algorithms to a wide range of computationally hard problems, and the theoretical understanding of properties of ACO algorithms. This chapter reviews these developments and gives an overview of recent research trends in ACO.

Aspects of the BMS/CFT correspondence

Abstract: After a review of symmetries and classical solutions involved in the AdS3/CFT2 correspondence, we apply a similar analysis to asymptotically flat spacetimes at null infinity in 3 and 4 dimensions. In the spirit of two dimensional conformal field theory, the symmetry algebra of asymptotically flat spacetimes at null infinity in 4 dimensions is taken to be the semi-direct sum of supertranslations with infinitesimal local conformal transformations and not, as usually done, with the Lorentz algebra. As a first application, we derive how the symmetry algebra is realized on solution space. In particular, we work out the behavior of Bondi’s news tensor, mass and angular momentum aspects under local conformal transformations.

Temporal cavity solitons in one-dimensional Kerr media as bits in an all-optical buffer

Abstract: Temporal cavity solitons are packets of light persisting in a continuously driven nonlinear resonator. They are robust attracting states, readily excited through a phase-insensitive and wavelength-insensitive process. As such, they constitute an ideal support for bits in an optical buffer that would seamlessly combine three critical telecommunication functions, namely all-optical storage, all-optical reshaping and wavelength conversion. Here, with standard silica optical fibres, we report the first experimental observation of temporal cavity solitons. The cavity solitons are 4 ps long and are used to demonstrate storage of a data stream for more than a second. We also observe interactions of close cavity solitons, revealing for our set-up a potential capacity of up to 45,000 bits at 25 Gbit s−1. More fundamentally, cavity solitons are localized dissipative structures. Therefore, given that silica exhibits a pure instantaneous Kerr nonlinearity, our experiment constitutes one of the simplest examples of self-organization phenomena in nonlinear optics. Using standard silica optical fibres, scientists observe temporal cavity solitons — packets of light persisting in a continuously driven nonlinear resonator. Cavity solitons 4 ps long are reported and used to demonstrate storage of a data stream for more than a second. The findings represent one of the simplest examples of self-organization phenomena in nonlinear optics.

The BioPAX community standard for pathway data sharing

Abstract: Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.

Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.

Abstract: In mouse, a subset of dendritic cells (DCs) known as CD8alpha+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8alpha+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8alpha+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8alpha+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8alpha+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell-derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.

The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis

Abstract: This is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. The continent of Africa experiences the bulk of the global malaria burden due in part to the presence of the An. gambiae complex. Anopheles gambiae is one of four DVS within the An. gambiae complex, the others being An. arabiensis and the coastal An. merus and An. melas. There are a further three, highly anthropophilic DVS in Africa, An. funestus, An. moucheti and An. nili. Conversely, across Europe and the Middle East, malaria transmission is low and frequently absent, despite the presence of six DVS. To help control malaria in Africa and the Middle East, or to identify the risk of its re-emergence in Europe, the contemporary distribution and bionomics of the relevant DVS are needed. A contemporary database of occurrence data, compiled from the formal literature and other relevant resources, resulted in the collation of information for seven DVS from 44 countries in Africa containing 4234 geo-referenced, independent sites. In Europe and the Middle East, six DVS were identified from 2784 geo-referenced sites across 49 countries. These occurrence data were combined with expert opinion ranges and a suite of environmental and climatic variables of relevance to anopheline ecology to produce predictive distribution maps using the Boosted Regression Tree (BRT) method. The predicted geographic extent for the following DVS (or species/suspected species complex*) is provided for Africa: Anopheles (Cellia) arabiensis, An. (Cel.) funestus*, An. (Cel.) gambiae, An. (Cel.) melas, An. (Cel.) merus, An. (Cel.) moucheti and An. (Cel.) nili*, and in the European and Middle Eastern Region: An. (Anopheles) atroparvus, An. (Ano.) labranchiae, An. (Ano.) messeae, An. (Ano.) sacharovi, An. (Cel.) sergentii and An. (Cel.) superpictus*. These maps are presented alongside a bionomics summary for each species relevant to its control.

Symmetries of asymptotically flat four-dimensional spacetimes at null infinity revisited.

Abstract: It is shown that the symmetry algebra of asymptotically flat spacetimes at null infinity in 4 dimensions should be taken as the semidirect sum of supertranslations with infinitesimal local conformal transformations and not, as usually done, with the Lorentz algebra. As a consequence, two-dimensional conformal field theory techniques will play as fundamental a role in this context of direct physical interest as they do in three-dimensional anti-de Sitter gravity.

Iterated Local Search: Framework and Applications

Abstract: The key idea underlying iterated local search is to focus the search not on the full space of all candidate solutions but on the solutions that are returned by some underlying algorithm, typically a local search heuristic. The resulting search behavior can be characterized as iteratively building a chain of solutions of this embedded algorithm. The result is also a conceptually simple metaheuristic that nevertheless has led to state-of-the-art algorithms for many computationally hard problems. In fact, very good performance is often already obtained by rather straightforward implementations of the metaheuristic. In addition, the modular architecture of iterated local search makes it very suitable for an algorithm engineering approach where, progressively, the algorithms’ performance can be further optimized. Our purpose here is to give an accessible description of the underlying principles of iterated local search and a discussion of the main aspects that need to be taken into account for a successful application of it. In addition, we review the most important applications of this method and discuss its relationship to other metaheuristics.

Nonlocality and communication complexity

Abstract: Quantum information processing is the emerging field that defines and realizes computing devices that make use of quantum mechanical principles, like the superposition principle, entanglement, and interference. Until recently the common notion of computing was based on classical mechanics, and did not take into account all the possibilities that physically-realizable computing devices offer in principle. The field gained momentum after Peter Shor developed an efficient algorithm for factoring numbers, demonstrating the potential computing powers that quantum computing devices can unleash. In this review we study the information counterpart of computing. It was realized early on by Holevo, that quantum bits, the quantum mechanical counterpart of classical bits, cannot be used for efficient transformation of information, in the sense that arbitrary k-bit messages can not be compressed into messages of k − 1 qubits. The abstract form of the distributed computing setting is called communication complexity. It studies the amount of information, in terms of bits or in our case qubits, that two spatially separated computing devices need to exchange in order to perform some computational task. Surprisingly, quantum mechanics can be used to obtain dramatic advantages for such tasks. We review the area of quantum communication complexity, and show how it connects the foundational physics questions regarding non-locality with those of communication complexity studied in theoretical computer science. The first examples exhibiting the advantage of the use of qubits in distributed information-processing tasks were based on non-locality tests. However, by now the field has produced strong and interesting quantum protocols and algorithms of its own that demonstrate that entanglement, although it cannot be used to replace communication, can be used to reduce the communication exponentially. In turn, these new advances yield a new outlook on the foundations of physics, and could even yield new proposals for experiments that test the foundations of physics.

Nonlinear W ∞ as asymptotic symmetry of three-dimensional higher spin AdS gravity

Abstract: We investigate the asymptotic symmetry algebra of (2+1)-dimensional higher spin, anti-de Sitter gravity. We use the formulation of the theory as a Chern-Simons gauge theory based on the higher spin algebra hs(1, 1). Expanding the gauge connection around asymptotically anti-de Sitter spacetime, we specify consistent boundary conditions on the higher spin gauge fields. We then study residual gauge transformation, the corresponding surface terms and their Poisson bracket algebra. We find that the asymptotic symmetry algebra is a nonlinearly realized W ∞ algebra with classical central charges. We discuss implications of our results to quantum gravity and to various situations in string theory.

Clinical review: Scoring systems in the critically ill

Abstract: General illness severity scores are widely used in the ICU to predict outcome, characterize disease severity and degree of organ dysfunction, and assess resource use. In this article we review the most commonly used scoring systems in each of these three groups. We examine the history of the development of the initial major systems in each group, discuss the construction of subsequent versions, and, when available, provide recent comparative data regarding their performance. Importantly, the different types of scores should be seen as complementary, rather than competitive and mutually exclusive. It is possible that their combined use could provide a more accurate indication of disease severity and prognosis. All these scoring systems will need to be updated with time as ICU populations change and new diagnostic, therapeutic and prognostic techniques become available.

Bibliometric indicators: quality measurements of scientific publication.

Abstract: Bibliometrics is a set of mathematical and statistical methods used to analyze and measure the quantity and quality of books, articles, and other forms of publications. There are three types of bibliometric indicators: quantity indicators, which measure the productivity of a particular researcher; quality indicators, which measure the quality (or "performance") of a researcher's output; and structural indicators, which measure connections between publications, authors, and areas of research. Bibliometric indicators are especially important for researchers and organizations, as these measurements are often used in funding decisions, appointments, and promotions of researchers. As more and more scientific discoveries occur and published research results are read and then quoted by other researchers, bibliometric indicators are becoming increasingly important. This article provides an overview of the currently used bibliometric indicators and summarizes the critical elements and characteristics one should be aware of when evaluating the quantity and quality of scientific output.

The international limits and population at risk of Plasmodium vivax transmission in 2009

Abstract: Background: A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. Methodology: The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (,0.1 case per 1,000 people per annum (p.a.)) and stable ($0.1 case per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics. Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands). The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009. The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait. It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission. The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially. Conclusions: After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia. The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers. The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.