Long-term intracerebral inflammatory response after traumatic brain injury

Epidemiological and pathological studies suggest that head injury is a significant risk factor for subsequent neurodegeneration and cognitive decline in later life. The precise mechanisms for the development of post-traumatic neurodegenerative change are unclear but we hypothesize that persistence of inflammatory processes in the brain may play a key role and that some individuals are more susceptible to such changes based on their genetic make-up. In support of this hypothesis we present evidence of persistent elevated microglial activity in long-term survivors of head injury and the suggestion of an association between the extent of this activity and interleukin-1 genotype

Bilateral carotid aneurysms unmasked by severe hypopituitarism.

We describe a patient who initially presented with severe hyponatraemia and grand mal seizures, without any focal neurological symptoms. The final diagnosis was that of giant bilateral carotid aneurysms extending into the sella turcica with anterior hypopituitarism. To the best of our knowledge, this is the first case report of symmetrical carotid aneurysms manifested exclusively by an acute endocrine emergency with none of the concomitant usual focal signs such as headache, failing vision, oculomotor palsy or subarachnoid hemorrhage

Genome-wide and fine-resolution association analysis of malaria in West Africa

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 association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations