Differential impact of severe drought on infant mortality in two sympatric neotropical primates

Extreme climate events can have important consequences for the dynamics of natural populations, and severe droughts are predicted to become more common and intense due to climate change. We analysed infant mortality in relation to drought in two primate species (white-faced capuchins, Cebus capucinus imitator, and Geoffroy's spider monkeys, Ateles geoffroyi) in a tropical dry forest in northwestern Costa Rica. Our survival analyses combine several rare and valuable long-term datasets, including long-term primate life-history, landscape-scale fruit abundance, food-tree mortality, and climate conditions. Infant capuchins showed a threshold mortality response to drought, with exceptionally high mortality during a period of intense drought, but not during periods of moderate water shortage. By contrast, spider monkey females stopped reproducing during severe drought, and the mortality of infant spider monkeys peaked later during a period of low fruit abundance and high food-tree mortality linked to the drought. These divergent patterns implicate differing physiology, behaviour or associated factors in shaping species-specific drought responses. Our findings link predictions about the Earth's changing climate to environmental influences on primate mortality risk and thereby improve our understanding of how the increasing severity and frequency of droughts will affect the dynamics and conservation of wild primates

Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

A comparison of benzodiazepine and related drug use in Nova Scotia and Australia

Objective: Benzodiazepines can be a problem if used for long periods, or in at-risk populations, such as the elderly. We compared the use of benzodiazepine and related prescription medicines in Nova Scotia and Australia

Timescales of Massive Human Entrainment

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here a successful example of this type of collaboration in the field of dementia.</p> <p>Methods</p> <p>The Donepezil Data Repository comprised 18 randomised, controlled trials conducted between 1991 and 2005. The project team at Pfizer determined that the data mining process should be guided by a diverse group of leading Alzheimer's disease clinical researchers called the "Expert Working Group." After development of a list of potential faculty members, invitations were extended and a group of seven members was assembled. The Working Group met regularly with Eisai/Pfizer clinicians and statisticians to discuss the data, identify issues that were currently of interest in the academic and clinical communities that might lend themselves to investigation using these data, and note gaps in understanding or knowledge of Alzheimer's disease that these data could address. Leadership was provided by the Pfizer Clinical Development team leader; Working Group members rotated responsibility for being lead and co-lead for each investigation and resultant publication.</p> <p>Results</p> <p>Six manuscripts, each published in a leading subspecialty journal, resulted from the group's work. Another project resulted in poster presentations at international congresses and two were cancelled due to resource constraints.</p> <p>Conclusions</p> <p>The experience represents a particular approach to optimising the value of data mining of large clinical trial databases for the combined purpose of furthering clinical research and improving patient care. Fruitful collaboration between industry and academia was fostered while the donepezil data repository was used to advance clinical and scientific knowledge. The Expert Working Group approach warrants consideration as a blueprint for conducting similar research ventures in the future.</p

Web Queries as a Source for Syndromic Surveillance

In the field of syndromic surveillance, various sources are exploited for outbreak detection, monitoring and prediction. This paper describes a study on queries submitted to a medical web site, with influenza as a case study. The hypothesis of the work was that queries on influenza and influenza-like illness would provide a basis for the estimation of the timing of the peak and the intensity of the yearly influenza outbreaks that would be as good as the existing laboratory and sentinel surveillance. We calculated the occurrence of various queries related to influenza from search logs submitted to a Swedish medical web site for two influenza seasons. These figures were subsequently used to generate two models, one to estimate the number of laboratory verified influenza cases and one to estimate the proportion of patients with influenza-like illness reported by selected General Practitioners in Sweden. We applied an approach designed for highly correlated data, partial least squares regression. In our work, we found that certain web queries on influenza follow the same pattern as that obtained by the two other surveillance systems for influenza epidemics, and that they have equal power for the estimation of the influenza burden in society. Web queries give a unique access to ill individuals who are not (yet) seeking care. This paper shows the potential of web queries as an accurate, cheap and labour extensive source for syndromic surveillance