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Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.
Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel – PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.
Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders.
The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.
These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.
Sir George Smart (1776–1867), conductor, composer, singing teacher and organist, was a central figure in nineteenth-century British musical life. He is best remembered as one of the founder members of the Philharmonic Society, for which he often conducted. Notably, in 1826 he presided over the first performance in England of Beethoven's ninth symphony. Smart was also much in demand as a conductor at the major English musical festivals and on royal occasions. These edited journal entries, first published in 1907, provide insightful accounts of concert life at the time, and they are particularly valuable for Smart's detailed observations - gathered during his extensive tour of 1825 - on musical practice in Europe, including conducting methods and performing speeds. The journal extracts end in 1845 with an account of Smart's visit to Bonn for the unveiling of Beethoven's statue.