Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

“The war is over – and I must go” Egon Schiele, 1890–1918.

     

The distribution and evolutionary history of the PRP8 intein

Background  

We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal.     

Giving the Forest Eyes: The Benefits of Using Camera Traps to Study Unhabituated Chimpanzees (Pan troglodytes verus) in Southeastern Senegal

Habituation has been the standard methodology used to study the natural history of great apes and other primates. Habituation has invaluable strengths, particularly in quantity and diversity of data collected, but along with these come substantial weaknesses, i.e., costs both in time and effort, health risks, and potential exposure of subjects to poaching. With new technologies, we are able to extend our studies beyond the limitations of habituation; camera traps are one technology that can be used to study unhabituated primate groups. In this study we used eight camera traps over the course of 2 yr (1542 camera trap days) to capture thousands of still images of West African savanna chimpanzees (Pan troglodytes verus) in the Falémé region of southeastern Senegal. Images corroborated behavioral observations from habituated chimpanzees at the Fongoli site, where researchers have observed nocturnal activity and cave use. The cameras also captured interspecies interactions at water sources during the dry season and allowed us to determine demographic composition and minimum community size. The photographs provide data on local fauna, including predators (Panthera pardus pardus, Panthera leo senegalesis, and Crocuta crocuta), potential prey, and competitor species (Papio papio, Cercopithecus aethiops, and Erythrocebus patas). As primate habitat across Africa is further threatened and human–wildlife conflict increases, camera trapping could be used as an essential conservation tool, expanding studies of primates without exacerbating potential threats to the species.     

Differences Between Vervets (Cercopithecus aethiops) and Patas Monkeys (Erythrocebus patas) in Agonistic Interactions Between Adult Females

We examined agonistic interactions between adult females in wild, unprovisioned patas monkeys (Erythrocebus patas) and vervets (Cercopithecus aethiops). The dominance hierarchy of patas is far less clear than that of vervets. Patas had fewer interactions per dyad, fewer dyads with interactions, and a high percentage (18%) of reversals in which lower-ranking females won in agonistic interactions with higher-ranking females. Although the rank ordering of the kinds of interactions patas and vervets displayed is similar, with avoidance being the most frequently observed agonistic response to approaches by other females, patas were chased and supplanted more often than vervets were. The resources over which females were supplanted also differ between species. Supplants over food comprise smaller proportion of total supplants patas than for vervets. Patas appear to feed on less usurpable foods than vervets. We conclude that (1) Erythrocebus and Cercopithecus spp., except C. aethiops, should not be categorized with other Cercopithecinae, and C. aethiops should not be categorized with other Cercopithecus spp. and Erythrocebus, in discussions and analyses of relationships between females within groups and (2) ecological conditions, i.e., usurpability of foods, can override phylogenetic history as the selective pressure determining the nature of female competitive relationships within groups.     

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

Background

Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates.

Methods/Design

This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae.

Discussion

Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov Identifier: NCT01255215     

Savanna chimpanzees, Pan troglodytes verus, hunt with tools

Although tool use is known to occur in species ranging from naked mole rats [1] to owls [2], chimpanzees are the most accomplished tool users [3-5]. The modification and use of tools during hunting, however, is still considered to be a uniquely human trait among primates. Here, we report the first account of habitual tool use during vertebrate hunting by nonhumans. At the Fongoli site in Senegal, we observed ten different chimpanzees use tools to hunt prosimian prey in 22 bouts. This includes immature chimpanzees and females, members of age-sex classes not normally characterized by extensive hunting behavior. Chimpanzees made 26 different tools, and we were able to recover and analyze 12 of these. Tool construction entailed up to five steps, including trimming the tool tip to a point. Tools were used in the manner of a spear, rather than a probe or rousing tool. This new information on chimpanzee tool use has important implications for the evolution of tool use and construction for hunting in the earliest hominids, especially given our observations that females and immature chimpanzees exhibited this behavior more frequently than adult males.     

Development of cell surface saccharides on embryonic pancreatic cells

Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life.     

Do "savanna" chimpanzees consume C4 resources?

Several stable carbon isotopic studies have shown that South African australopiths consumed significant quantities of C(4) resources (tropical grasses, sedges, or animals that eat those foods), but relatively little is known about the consumption of such resources by chimpanzees. Here, we present stable carbon isotopic data for 36 chimpanzee hair samples from Fongoli, one of the driest and most open areas inhabited by chimpanzees. These data suggest that the Fongoli chimpanzees consume little in the way of C(4) vegetation or animals that eat such vegetation, even though these resources are locally abundant and preferred fruits are more widely scattered than at most chimpanzee study sites. The homogeneity of the Fongoli results is especially striking and recalls the narrow isotopic distribution of stenotopic savanna mammals. This is in stark contrast to what has been observed for australopiths, which had highly variable diets and consumed about 35% C(4) vegetation on average. Carbon isotope data for modern and fossil Papio depict a dietarily variable genus with a tendency to consume C(4) vegetation. This trophic flexibility, or willingness to consume C(4) savanna resources, may make Papio a more profitable ecological analog for australopiths than chimpanzees.