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CONTEXT The geographical distributions of hemoglobin S (HbS), hemoglobin C (HbC), and alpha+-thalassemia (-alpha) strongly suggest balancing selection with malaria. However, whereas several studies indicate that the HbS carrier state protects against all major forms of clinical malaria, malaria protection on clinical grounds has been more difficult to(More)
We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of(More)
BACKGROUND The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell(More)
The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one(More)
BACKGROUND Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in(More)
BACKGROUND Data from the largest randomized, controlled trial for the treatment of children hospitalized with severe malaria were used to identify such predictors of a poor outcome from severe malaria. METHODS African children (<15 years) with severe malaria participated in a randomized comparison of parenteral artesunate and parenteral quinine in 9(More)
BACKGROUND Early recognition of children at highest risk of dying and the targeting of appropriate drug therapy are vital to the improvement of paediatric care in developing countries. This will rely upon the development of simple clinically-based algorithms and treatment guidelines. AIM To determine the role of bacteraemia in children presenting with(More)
The mammalian pacemaker in the suprachiasmatic nucleus (SCN) contains a population of neural oscillators capable of sustaining cell-autonomous rhythms in gene expression and electrical firing. A critical question for understanding pacemaker function is how SCN oscillators are organized into a coherent tissue capable of coordinating circadian rhythms in(More)
Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these signaling mechanisms, we developed a functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with(More)
Daily rhythms in behavior and physiology are programmed by a hierarchical collection of biological clocks located throughout the brain and body, known as the circadian system. Mounting evidence indicates that disruption of circadian regulation is associated with a wide variety of adverse health consequences, including increased risk for premature death,(More)