Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes

The predicted secondary structure of sub-genomic RNA in dengue virus defective interfering (D.I.) particles from patients, or generated in vitro, resembled that of the 3′ and 5′ regions of wild type dengue virus (DENV) genomes. While these structures in the sub-genomic RNA were found to be essential for its replication, their nucleotide sequences were not, so long as any new sequences maintained wild type RNA secondary structure. These observations suggested that these sub-genomic fragments of RNA from dengue viruses were replicated in the same manner as the full length genomes of their wild type, “helper”, viruses and that they probably represent the smallest fragments of DENV RNA that can be replicated during a natural infection. While D.I. particles containing sub-genomic RNA are completely parasitic, the relationship between wild type and D.I. DENV may be symbiotic, with the D.I. particles enhancing the transmission of infectious DENV.

The Wzy O-antigen polymerase of Yersinia pseudotuberculosis O:2a has a dependence on the Wzz chain-length determinant for efficient polymerization

Lipopolysaccharide is a major immunogenic structure for the pathogen Yersinia pseudotuberculosis, which contains the O-specific polysaccharide (OPS) that is presented on the cell surface. The OPS contains many repeats of the oligosaccharide O-unit and exhibits a preferred modal chain length that has been shown to be crucial for cell protection in Yersinia. It is well established that the Wzz protein determines the preferred chain length of the OPS, and in its absence, the polymerization of O units by the Wzy polymerase is uncontrolled. However, for Y. pseudotuberculosis, a wzz mutation has never been described. In this study, we examine the effect of Wzz loss in Y. pseudotuberculosis serotype O:2a and compare the lipopolysaccharide chain-length profile to that of Escherichia coli serotype O111. In the absence of Wzz, the lipopolysaccharides of the two species showed significant differences in Wzy polymerization. Yersinia pseudotuberculosis O:2a exhibited only OPS with very short chain lengths, which is atypical of wzz-mutant phenotypes that have been observed for other species. We hypothesise that the Wzy polymerase of Y. pseudotuberculosis O:2a has a unique default activity in the absence of the Wzz, revealing the requirement of Wzz to drive O-unit polymerization to greater lengths.

Numerical investigation of motion and deformation of a single red blood cell in a stenosed capillary

It is generally assumed that influence of the red blood cells (RBCs) is predominant in blood rheology. The healthy RBCs are highly deformable and can thus easily squeeze through the smallest capillaries having internal diameter less than their characteristic size. On the other hand, RBCs infected by malaria or other diseases are stiffer and so less deformable. Thus it is harder for them to flow through the smallest capillaries. Therefore, it is very important to critically and realistically investigate the mechanical behavior of both healthy and infected RBCs which is a current gap in knowledge. The motion and the steady state deformed shape of the RBCs depend on many factors, such as the geometrical parameters of the capillary through which blood flows, the membrane bending stiffness and the mean velocity of the blood flow. In this study, motion and deformation of a single two-dimensional RBC in a stenosed capillary is explored by using smoothed particle hydrodynamics (SPH) method. An elastic spring network is used to model the RBC membrane, while the RBC's inside fluid and outside fluid are treated as SPH particles. The effect of RBC's membrane stiffness (kb), inlet pressure (P) and geometrical parameters of the capillary on the motion and deformation of the RBC is studied. The deformation index, RBC's mean velocity and the cell membrane energy are analyzed when the cell passes through the stenosed capillary. The simulation results demonstrate that the kb, P and the geometrical parameters of the capillary have a significant impact on the RBCs' motion and deformation in the stenosed section.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Impact of a stroke unit on length of hospital stay and in-hospital case fatality

Background and Purpose Randomized trials have demonstrated reduced morbidity and mortality with stroke unit care; however, the effect on length of stay, and hence the economic benefit, is less well-defined. In 2001, a multidisciplinary stroke unit was opened at our institution. We observed whether a stroke unit reduces length of stay and in-hospital case fatality when compared to admission to a general neurology/medical ward. Methods A retrospective study of 2 cohorts in the Foothills Medical Center in Calgary was conducted using administrative databases. We compared a cohort of stroke patients managed on general neurology/medical wards before 2001, with a similar cohort of stroke patients managed on a stroke unit after 2003. The length of stay was dichotomized after being centered to 7 days and the Charlson Index was dichotomized for analysis. Multivariable logistic regression was used to compare the length of stay and case fatality in 2 cohorts, adjusted for age, gender, and patient comorbid conditions defined by the Charlson Index. Results Average length of stay for patients on a stroke unit (n=2461) was 15 days vs 19 days for patients managed on general neurology/medical wards (n=1567). The proportion of patients with length of stay >7 days on general neurology/medical wards was 53.8% vs 44.4% on the stroke unit (difference 9.4%; P<0.0001). The adjusted odds of a length of stay >7 days was reduced by 30% (P<0.0001) on a stroke unit compared to general neurology/medical wards. Overall in-hospital case fatality was reduced by 4.5% with stroke unit care. Conclusions We observed a reduced length of stay and reduced in-hospital case-fatality in a stroke unit compared to general neurology/medical wards.

4D deformation modeling of cortical disease progression in Alzheimer's dementia

This work describes the development of a model of cerebral atrophic changes associated with the progression of Alzheimer's disease (AD). Linear registration, region-of-interest analysis, and voxel-based morphometry methods have all been employed to elucidate the changes observed at discrete intervals during a disease process. In addition to describing the nature of the changes, modeling disease-related changes via deformations can also provide information on temporal characteristics. In order to continuously model changes associated with AD, deformation maps from 21 patients were averaged across a novel z-score disease progression dimension based on Mini Mental State Examination (MMSE) scores. The resulting deformation maps are presented via three metrics: local volume loss (atrophy), volume (CSF) increase, and translation (interpreted as representing collapse of cortical structures). Inspection of the maps revealed significant perturbations in the deformation fields corresponding to the entorhinal cortex (EC) and hippocampus, orbitofrontal and parietal cortex, and regions surrounding the sulci and ventricular spaces, with earlier changes predominantly lateralized to the left hemisphere. These changes are consistent with results from post-mortem studies of AD.

Best individual template selection from deformation tensor minimization

We study the influence of the choice of template in tensor-based morphometry. Using 3D brain MR images from 10 monozygotic twin pairs, we defined a tensor-based distance in the log-Euclidean framework [1] between each image pair in the study. Relative to this metric, twin pairs were found to be closer to each other on average than random pairings, consistent with evidence that brain structure is under strong genetic control. We also computed the intraclass correlation and associated permutation p-value at each voxel for the determinant of the Jacobian matrix of the transformation. The cumulative distribution function (cdf) of the p-values was found at each voxel for each of the templates and compared to the null distribution. Surprisingly, there was very little difference between CDFs of statistics computed from analyses using different templates. As the brain with least log-Euclidean deformation cost, the mean template defined here avoids the blurring caused by creating a synthetic image from a population, and when selected from a large population, avoids bias by being geometrically centered, in a metric that is sensitive enough to anatomical similarity that it can even detect genetic affinity among anatomies.

Effect of bond length on the behaviour of CFRP strengthened concrete-filled steel tubes under transverse impact

Concrete-filled steel tubular (CFST) columns have shown great potential as axial load carrying member and used widely in many mission critical infrastructures. However, attention is needed to strengthen these members where transverse impact force is expected to occur due to vehicle collisions. In this work, finite element (FE) model of carbon fibre reinforced polymer (CFRP) strengthened CFST columns are developed and the effect of CFRP bond length is investigated under transverse impact loading. Initially the numerical models have been validated by comparing impact test results from literature. The validated models are then used for detail parametric studies by varying the length of externally bonded CFRP composites. The parameters considered for this research are impact velocity, impact mass, CFRP modulus, adhesive type, and axial static loading. It has been observed that the effect of CFRP strengthening is consistent after an optimum effective bond length of CFRP wrapping. The effect of effective bond length has been studied for above parameters. The results show that, under combined axial static and transverse impact loads CFST columns can successfully prevent global buckling failure by strengthening only 34% of column length. Therefore, estimation of effective bond length is essential to utilise the CFRP composites cost effectively.

Influence of pipe length and flow rate on nano-particle deposition in laminar circular pipe flows

The Lagrangian particle tracking provides an effective method for simulating the deposition of nano- particles as well as micro-particles as it accounts for the particle inertia effect as well as the Brownian excitation. However, using the Lagrangian approach for simulating ultrafine particles has been limited due to computational cost and numerical difficulties. The aim of this paper is to study the deposition of nano-particles in cylindrical tubes under laminar condition using the Lagrangian particle tracking method. The commercial Fluent software is used to simulate the fluid flow in the pipes and to study the deposition and dispersion of nano-particles. Different particle diameters as well as different pipe lengths and flow rates are examined. The results show good agreement between the calculated deposition efficiency and different analytic correlations in the literature. Furthermore, for the nano-particles with higher diameters and when the effect of inertia has a higher importance, the calculated deposition efficiency by the Lagrangian method is less than the analytic correlations based on Eulerian method due to statistical error or the inertia effect.

Implementation of a chest pain management service improves patient care and reduces length of stay

Objective Chest pain is one of the most common complaints in patients presenting to an emergency department. Delays in management due to a lack of readily available objective tests to risk stratify patients with possible acute coronary syndromes can lead to an unnecessarily lengthy admission placing pressure on hospital beds or inappropriate discharge. The need for a co-ordinated system of clinical management based on enhanced communication between departments, timely and appropriate triage, clinical investigation, diagnosis, and treatment was identified. Methods An evidence-based Chest Pain Management Service and clinical pathway were developed and implemented, including the introduction of after-hours exercise stress testing. Results Between November 2005 and March 2013, 5662 patients were managed according to a Chest Pain Management pathway resulting in a reduction of 5181 admission nights by more timely identification of patients at low risk who could then be discharged. In addition, 1360 days were avoided in high-risk patients who received earlier diagnosis and treatment. Conclusions The creation of a Chest Pain Management pathway and the extended exercise stress testing service resulted in earlier discharge for low-risk patients; and timely treatment for patients with positive and equivocal exercise stress test results. This service demonstrated a significant saving in overnight admissions.

A directed continuous time random walk model with jump length depending on waiting time

In continuum one-dimensional space, a coupled directed continuous time random walk model is proposed, where the random walker jumps toward one direction and the waiting time between jumps affects the subsequent jump. In the proposed model, the Laplace-Laplace transform of the probability density function P(x,t) of finding the walker at position at time is completely determined by the Laplace transform of the probability density function φ(t) of the waiting time. In terms of the probability density function of the waiting time in the Laplace domain, the limit distribution of the random process and the corresponding evolving equations are derived.

A simple method for estimating growth parameters from multiple length-frequency data in presence of continuous recruitment

The extended recruitment season for short-lived species such as prawns biases the estimation of growth parameters from length-frequency data when conventional methods are used. We propose a simple method for overcoming this bias given a time series of length-frequency data. The difficulties arising from extended recruitment are eliminated by predicting the growth of the succeeding samples and the length increments of the recruits in previous samples. This method requires that some maximum size at recruitment can be specified. The advantages of this multiple length-frequency method are: it is simple to use; it requires only three parameters; no specific distributions need to be assumed; and the actual seasonal recruitment pattern does not have to be specified. We illustrate the new method with length-frequency data on the tiger prawn Penaeus esculentus from the north-western Gulf of Carpentaria, Australia.

Maximum likelihood estimation of mortality and growth with individual variability from multiple length-frequency data

We consider estimation of mortality rates and growth parameters from length-frequency data of a fish stock and derive the underlying length distribution of the population and the catch when there is individual variability in the von Bertalanffy growth parameter L-infinity. The model is flexible enough to accommodate 1) any recruitment pattern as a function of both time and length, 2) length-specific selectivity, and 3) varying fishing effort over time. The maximum likelihood method gives consistent estimates, provided the underlying distribution for individual variation in growth is correctly specified. Simulation results indicate that our method is reasonably robust to violations in the assumptions. The method is applied to tiger prawn data (Penaeus semisulcatus) to obtain estimates of natural and fishing mortality.

Effect of individual variability on estimation of population parameters from length-frequency data

We consider estimation of mortality rates and growth parameters from length-frequency data of a fish stock when there is individual variability in the von Bertalanffy growth parameter L-infinity and investigate the possible bias in the estimates when the individual variability is ignored. Three methods are examined: (i) the regression method based on the Beverton and Holt's (1956, Rapp. P.V. Reun. Cons. Int. Explor. Mer, 140: 67-83) equation; (ii) the moment method of Powell (1979, Rapp. PV. Reun. Int. Explor. Mer, 175: 167-169); and (iii) a generalization of Powell's method that estimates the individual variability to be incorporated into the estimation. It is found that the biases in the estimates from the existing methods are, in general, substantial, even when individual variability in growth is small and recruitment is uniform, and the generalized method performs better in terms of bias but is subject to a larger variation. There is a need to develop robust and flexible methods to deal with individual variability in the analysis of length-frequency data.