Efficient simulation of the spatial transmission dynamics of influenza

Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies over-estimated the within-country rate of spatial spread of pandemic influenza. As large spatially resolved data sets are constructed, the need for efficient simulation code with which to investigate the spatial patterns of the pandemic becomes clear. Here, we present a significant improvement to the efficiency of an individual based stochastic disease simulation framework commonly used in multiple previous studies. We quantify the efficiency of the revised algorithm and present an alternative parameterization of the model in terms of the basic reproductive number. We apply the model to the population of Taiwan and demonstrate how the location of the initial seed can influence spatial incidence profiles and the overall spread of the epidemic. Differences in incidence are driven by the relative connectivity of alternate seed locations. The ability to perform efficient simulation allows us to run a batch of simulations and take account of their average in real time. The averaged data are stable and can be used to differentiate spreading patterns that are not readily seen by only conducting a few runs. © 2010 Tsai et al.published_or_final_versio

A critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer

Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single gene classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single gene classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single gene classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single gene sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single gene classifiers for predicting outcome in breast cancer

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Ipl1/aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis

Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics

Analysis of factors influencing the ultrasonic fetal weight estimation

Objective: The aim of our study was the evaluation of sonographic fetal weight estimation taking into consideration 9 of the most important factors of influence on the precision of the estimation. Methods: We analyzed 820 singleton pregnancies from 22 to 42 weeks of gestational age. We evaluated 9 different factors that potentially influence the precision of sonographic weight estimation ( time interval between estimation and delivery, experts vs. less experienced investigator, fetal gender, gestational age, fetal weight, maternal BMI, amniotic fluid index, presentation of the fetus, location of the placenta). Finally, we compared the results of the fetal weight estimation of the fetuses with poor scanning conditions to those presenting good scanning conditions. Results: Of the 9 evaluated factors that may influence accuracy of fetal weight estimation, only a short interval between sonographic weight estimation and delivery (0-7 vs. 8-14 days) had a statistically significant impact. Conclusion: Of all known factors of influence, only a time interval of more than 7 days between estimation and delivery had a negative impact on the estimation

Modulated Instability in Five-Dimensional U(1) Charged AdS Black Hole with R**2-term

We study the effect of R**2 term to the modulated instability in the U(1) charged black hole in five-dimensional Anti-de Sitter space-time. We consider the first-order corrections of R**2 term to the background and the linear order perturbations in the equations of motion. From the analysis, we clarify the effect of R**2 term in the modulated instability, and conclude that fluctuations are stable in the whole bulk in the range of values the coefficient of R**2 term can take.Comment: 19 pages, 1 figures; (v4) Published version in JHE

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Clinical characteristics and prognosis of acute bacterial meningitis in elderly patients over 65: a hospital-based study

<p>Abstract</p> <p>Background</p> <p>To examine the clinical characteristics of bacterial meningitis in elderly patients.</p> <p>Methods</p> <p>261 patients with adult bacterial meningitis (ABM), collected during a study period of 11 years (2000-2010), were included for study. Among them, 87 patients aged ≥ 65 years and were classified as the elderly group. The clinical and laboratory characteristics and prognostic factors were analyzed, and a clinical comparison with those of non-elderly ABM patients was also made.</p> <p>Results</p> <p>The 87 elderly ABM patients were composed of 53 males and 34 females, aged 65-87 years old (median = 71 years). Diabetes mellitus (DM) was the most common underlying condition (34%), followed by end stage renal disease (7%), alcoholism (4%) and malignancies (4%). Fever was the most common clinical manifestation (86%), followed by altered consciousness (62%), leukocytosis (53%), hydrocephalus (38%), seizure (30%), bacteremia (21%) and shock (11%). Thirty-nine of these 87 elderly ABM patients had spontaneous infection, while the other 48 had post-neurosurgical infection. Forty-four patients contracted ABM in a community-acquired state, while the other 43, a nosocomial state. The therapeutic results of the 87 elderly ABM patients were that 34 patients expired and 53 patients survived. The comparative results of the clinical and laboratory characteristics between the elderly and non-elderly ABM patients showed that only peripheral blood leukocytosis was significant. Presence of shock and seizure were significant prognostic factors of elderly ABM patients.</p> <p>Conclusions</p> <p>Elderly ABM patients accounted for 34.8% of the overall ABM cases, and this relatively high incidence rate may signify the future burden of ABM in the elderly population in Taiwan. The relative frequency of implicated pathogens of elderly ABM is similar to that of non-elderly ABM. Compared with non-elderly patients, the elderly ABM patients have a significantly lower incidence of peripheral blood leukocytosis. The mortality rate of elderly ABM remains high, and the presence of shock and seizures are important prognostic factors.</p

Does primary brachial plexus surgery alter palliative tendon transfer surgery outcomes in children with obstetric paralysis?

<p>Abstract</p> <p>Background</p> <p>The surgical management of obstetrical brachial plexus palsy can generally be divided into two groups; early reconstructions in which the plexus or affected nerves are addressed and late or palliative reconstructions in which the residual deformities are addressed. Tendon transfers are the mainstay of palliative surgery. Occasionally, surgeons are required to utilise already denervated and subsequently reinnervated muscles as motors. This study aimed to compare the outcomes of tendon transfers for residual shoulder dysfunction in patients who had undergone early nerve surgery to the outcomes in patients who had not.</p> <p>Methods</p> <p>A total of 91 patients with obstetric paralysis-related shoulder abduction and external rotation deficits who underwent a modified Hoffer transfer of the latissimus dorsi/teres major to the greater tubercle of the humerus tendon between 2002 and 2009 were retrospectively analysed. The patients who had undergone neural surgery during infancy were compared to those who had not in terms of their preoperative and postoperative shoulder abduction and external rotation active ranges of motion.</p> <p>Results</p> <p>In the early surgery groups, only the postoperative external rotation angles showed statistically significant differences (25 degrees and 75 degrees for total and upper type palsies, respectively). Within the palliative surgery-only groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles. The significant differences between the early surgery groups and the palliative surgery groups with total palsy during the preoperative period diminished postoperatively (p < 0.05 and p > 0.05, respectively) for abduction but not for external rotation. Within the upper type palsy groups, there were no significant differences between the preoperative and postoperative abduction and external rotation angles.</p> <p>Conclusions</p> <p>In this study, it was found that in patients with total paralysis, satisfactory shoulder abduction values can be achieved with tendon transfers regardless of a previous history of neural surgery even if the preoperative values differ.</p