Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.DOI: http://dx.doi.org/10.7554/eLife.15085.001

This study shows that falls might be reduced in a multidisciplinary fall-prevention program, but the results are not definitive because of the borderline significance achieved and the variable length of stay. More research on fall prevention in hospital is required, particularly as to what interventions, if any, are effective at reducing falls in this group of patients.

Abstract.A growing number of research projects in academia and industry have recently started to develop lifelike agents as a new metaphor for highly personalised human-machine communication. A strong argument in favour of using such characters in the interface is the fact that they make humancomputer interaction more enjoyable and allow for communication styles common in human-human dialogue. Our earlier work in this area has concentrated on the development of animated presenters that show, explain, and verbally comment textual and graphical output on a window-based interface. Even though first empirical studies have been very encouraging and revealed a strong affective impact of our Personas [23], they also suggest that simply embodying an interface agent is insufficient. To come across as believable, an agent needs to incorporate a deeper model of personality and emotions, and in particular directly connect these two concepts.

Tanev Stoyan et al., « How do value co-creation activities relate to the perception of firms' innovativeness? » ,