Gastrointestinal pathogen distribution in symptomatic children in Sydney, Australia

There is limited information on the causes of paediatric diarrhoea in Sydney. This cross-sectional study used clinical and microbiological data to describe the clinical features and pathogens associated with gastrointestinal illnesses for children presenting to two major public hospitals in Sydney with diarrhoea, for the period January 2007-December 2010.Of 825 children who tested positive for an enteric pathogen, 430 medical records were reviewed. Adenovirus, norovirus and rotavirus were identified in 20.8%, 20.3% and 21.6% of reviewed cases, respectively. Younger children were more likely to have adenovirus and norovirus compared with rotavirus (P=0.001). More viruses were detected in winter than in the other three seasons (P=0.001). Rotavirus presented a distinct seasonal pattern with the lowest rates occurring in the warm months and peaking in the cooler months. Adenovirus showed a less consistent monthly trend, and norovirus detection increased in the cooler months (P=0.008). A decline in the number of rotavirus cases was observed after mid-2008.The majority of childhood diarrhoeal illnesses leading to hospital presentations in Sydney are caused by enteric viruses with most infections following clear seasonal patterns. However, a sustained decrease in the incidence of rotavirus infections has been observed over the study period. © 2012 Ministry of Health, Saudi Arabia

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Analytic provenance as constructs of behavioural markers for externalizing thinking processes in criminal intelligence analysis

Studying how analysts use interaction in visualization systems is an important part of evaluating how well these interactions support analysis needs, like generating insights or performing tasks. Analytic Provenance commonly known as interaction histories contains information about the sequence of choices that analysts make when exploring data or performing a task. This research work presents a compositional reductionist approach as a way of externalizing analyst’s thinking processes by using markers of analytical behaviour extracted from such interaction histories. Set of Behavioural Markers (BMs) have been identified through a workshop with domain experts and a systematic literature review to use them as cognitive attributes of imagination, insight, transparency, fluidity and rigour to enhance performance in criminal intelligence analysis. A low level semantic action sequence computation also has been proposed as a detection approach of identified BMs and found from computation that BMs can act as bridge between human cognition and computation through semantic interaction. This research work has addressed problems of existing qualitative experiments to extract these BMs through cognitive task analysis and found that the proposed computational technique can be a supplementary approach for validating experimental results

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Virtual environment navigation with look-around mode to explore new real spaces by people who are blind

Background. This paper examines the ability of people who are blind to construct a mental map and perform orientation tasks in real space by using Nintendo Wii technologies to explore virtual environments. The participant explores new spaces through haptic and auditory feedback triggered by pointing or walking in the virtual environments and later constructs a mental map, which can be used to navigate in real space. Methods. The study included 10 participants who were congenitally or adventitiously blind, divided into experimental and control groups. The research was implemented by using virtual environments exploration and orientation tasks in real spaces, using both qualitative and quantitative methods in its methodology. Results. The results show that the mode of exploration afforded to the experimental group is radically new in orientation and mobility training; as a result 60% of the experimental participants constructed mental maps that were based on map model, compared to only 30% of the control group participants. Conclusion. Using technology that enabled them to explore and to collect spatial information in a way that does not exist in real space influenced the ability of the experimental group to construct a mental map based on the map model

Superficial simplicity of the 2010 El Mayor–Cucapah earthquake of Baja California in Mexico

The geometry of faults is usually thought to be more complicated at the surface than at depth and to control the initiation, propagation and arrest of seismic ruptures. The fault system that runs from southern California into Mexico is a simple strike-slip boundary: the west side of California and Mexico moves northwards with respect to the east. However, the M_w 7.2 2010 El Mayor–Cucapah earthquake on this fault system produced a pattern of seismic waves that indicates a far more complex source than slip on a planar strike-slip fault. Here we use geodetic, remote-sensing and seismological data to reconstruct the fault geometry and history of slip during this earthquake. We find that the earthquake produced a straight 120-km-long fault trace that cut through the Cucapah mountain range and across the Colorado River delta. However, at depth, the fault is made up of two different segments connected by a small extensional fault. Both segments strike N130° E, but dip in opposite directions. The earthquake was initiated on the connecting extensional fault and 15 s later ruptured the two main segments with dominantly strike-slip motion. We show that complexities in the fault geometry at depth explain well the complex pattern of radiated seismic waves. We conclude that the location and detailed characteristics of the earthquake could not have been anticipated on the basis of observations of surface geology alone

A Status Report on Conflict Analysis in Mixed Integer Nonlinear Programming

Mixed integer nonlinear programs (MINLPs) are arguably among the hardest optimization problems, with a wide range of applications. MINLP solvers that are based on linear relaxations and spatial branching work similar as mixed integer programming (MIP) solvers in the sense that they are based on a branch-and-cut algorithm, enhanced by various heuristics, domain propagation, and presolving techniques. However, the analysis of infeasible subproblems, which is an important component of most major MIP solvers, has been hardly studied in the context of MINLPs. There are two main approaches for infeasibility analysis in MIP solvers: conflict graph analysis, which originates from artificial intelligence and constraint programming, and dual ray analysis. The main contribution of this short paper is twofold. Firstly, we present the first computational study regarding the impact of dual ray analysis on convex and nonconvex MINLPs. In that context, we introduce a modified generation of infeasibility proofs that incorporates linearization cuts that are only locally valid. Secondly, we describe an extension of conflict analysis that works directly with the nonlinear relaxation of convex MINLPs instead of considering a linear relaxation. This is work-in-progress, and this short paper is meant to present first theoretical considerations without a computational study for that part

Using Persuasive Technology to Increase Physical Activity in People With Chronic Obstructive Pulmonary Disease by Encouraging Regular Walking: A Mixed-Methods Study Exploring Opinions and Preferences

Background: People with chronic obstructive pulmonary disease (PwCOPD) often experience breathlessness and fatigue, making physical activity challenging. Although many persuasive technologies (such as mobile phone apps) have been designed to support physical activity among members of the general population, current technologies aimed at PwCOPD are underdeveloped and only use a limited range of persuasive technology design principles. Objective: The aim of this study was to explore how acceptable different persuasive technology design principles were considered to be in supporting and encouraging physical activity among PwCOPD. Methods: Three prototypes for mobile apps using different persuasive technology design principles as defined by the persuasive systems design (PSD) model—namely, dialogue support, primary task support, and social support—were developed. Opinions of these prototypes were explored through 28 interviews with PwCOPD, carers, and the health care professionals (HCPs) involved in their care and questionnaires completed by 87 PwCOPD. Participants also ranked how likely individual techniques (eg, competition) would be to convince them to use a technology designed to support physical activity. Data were analyzed using framework analysis, Friedman tests, and Wilcoxon signed rank tests and a convergent mixed methods design was used to integrate findings. Results: The prototypes for mobile apps were received positively by participants. The prototype that used a dialogue support approach was identified as the most likely to be used or recommended by those interviewed, and was perceived as more persuasive than both of the other prototypes (Z=−3.06, P=.002; Z=−5.50, P<.001) by those who completed the questionnaire. PwCOPD identified dialogue support and primary task support techniques as more likely to convince them to use a technology than social support techniques (Z=−5.00, P<.001; Z=−4.92, P<.001, respectively). Opinions of social support techniques such as competition and collaboration were divided. Conclusions: Dialogue support and primary task support approaches are considered to be both acceptable and likely to be persuasive by PwCOPD, carers, and HCPs. In the future, these approaches should be considered when designing apps to encourage physical activity by PwCOPD

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies