Time walkers and spatial dynamics of ageing information

The distribution of information is essential for living system's ability to coordinate and adapt. Random walkers are often used to model this distribution process and, in doing so, one effectively assumes that information maintains its relevance over time. But the value of information in social and biological systems often decay and must continuously be updated. To capture the spatial dynamics of ageing information, we introduce time walkers. A time walker moves like a random walker, but interacts with traces left by other walkers, some representing older information, some newer. The traces forms a navigable information landscape. We quantify the dynamical properties of time walkers moving on a two-dimensional lattice and the quality of the information landscape generated by their movements. We visualise the self-similar landscape as a river network, and show that searching in this landscape is superior to random searching and scales as the length of loop-erased random walks

Weighted distances in scale-free preferential attachment models

We study three preferential attachment models where the parameters are such that the asymptotic degree distribution has infinite variance. Every edge is equipped with a non-negative i.i.d. weight. We study the weighted distance between two vertices chosen uniformly at random, the typical weighted distance, and the number of edges on this path, the typical hopcount. We prove that there are precisely two universality classes of weight distributions, called the explosive and conservative class. In the explosive class, we show that the typical weighted distance converges in distribution to the sum of two i.i.d. finite random variables. In the conservative class, we prove that the typical weighted distance tends to infinity, and we give an explicit expression for the main growth term, as well as for the hopcount. Under a mild assumption on the weight distribution the fluctuations around the main term are tight.Comment: Revised version, results are unchanged. 30 pages, 1 figure. To appear in Random Structures and Algorithm

Percentile Queries in Multi-Dimensional Markov Decision Processes

Markov decision processes (MDPs) with multi-dimensional weights are useful to analyze systems with multiple objectives that may be conflicting and require the analysis of trade-offs. We study the complexity of percentile queries in such MDPs and give algorithms to synthesize strategies that enforce such constraints. Given a multi-dimensional weighted MDP and a quantitative payoff function $f$, thresholds $v_i$ (one per dimension), and probability thresholds $\alpha_i$, we show how to compute a single strategy to enforce that for all dimensions $i$, the probability of outcomes $\rho$ satisfying $f_i(\rho) \geq v_i$ is at least $\alpha_i$. We consider classical quantitative payoffs from the literature (sup, inf, lim sup, lim inf, mean-payoff, truncated sum, discounted sum). Our work extends to the quantitative case the multi-objective model checking problem studied by Etessami et al. in unweighted MDPs.Comment: Extended version of CAV 2015 pape

The use of initial dosing of gentamicin in the management of pyelonephritis/urosepsis: A retrospective study

Objective: The primary objective was to determine if initial empirical intravenous dosing of gentamicin improved patient’s outcomes in pyelonephritis/urosepsis compared with alternative IV antibiotic management. Design Retrospective cross-sectional descriptive study. Setting: Public TertiaryTeaching Hospital serving adults in an urban centre. Participants: All adult patient records with a recorded diagnosis of any of pyelonephritis/urosepsis, urinary tract infection, UTI, complicated urinary tract infection, bacteriuria, symptomatic bacteriuria and asymptomatic bacteriuria from 2nd February 2012 to 10th May 2014 were reviewed. Only patients treated with an empirical regimen of one or more IV antibiotics were included in the study. Main outcomes The primary outcomes were: duration of IV antibiotic treatment, time to resolution of symptoms and length of hospital stay (LOS). Secondary end points were: compliance with Therapeutic Guidelines: Antibiotic (electronic version) (eTG) for severe pyelonephritis/urosepsis and appropriateness of gentamicin use. Data analysis Univariate and multivariable associations between baseline and demographic variables and the main outcomes were performed using Chi-square tests and a General Linear Model using the SAS version 9.2 software. Results: Of 295 patients reviewed 152 were prescribed one or more IV antibiotics and included in the study. Approximately half of the patients (n = 73, 48%) were prescribed IV piperacillin/tazobactam (Tazocin), while gentamicin was prescribed for 66 patients (43.4%). Of the 152 patients evaluated, 49 (32%) were given gentamicin first. Multivariable regression analysis showed that duration of IV treatment was shorter for those aged over 70 (40.2 hours vs 85.5 hours for those aged up to 70; p = 0.0074), and those who received gentamicin as first line treatment (41.3 hours vs 89.8 hours for those not receiving any gentamicin; p = 0.0312). After adjustment for age and gentamicin administration, there appeared to be no significant difference in duration of IV treatment for any other independent variables. No significant associations between the independent variables (gentamicin, age, gender, comorbidities, and eTG compliance) and either time to resolution of symptoms (median: 68 hours) or hospital LOS (median: 5 days) were observed. Conclusions: Neither time to resolution of abnormal symptoms nor length of stay were significantly influenced by an initial dose of gentamicin when the data were subjected to multivariable analysis. The age of the patient and pattern of gentamicin treatment were the dominant factors associated with duration of IV antibiotics. Piperacillin/tazobactam is not recommended in treatment guidelines for pyelonephritis/urosepsis but was the most commonly prescribed IV antibiotic. This requires review by the appropriate hospital clinicians

Gene Expression Pattern Analysis of Anterior Hox Genes during Zebrafish (Danio rerio) Embryonic Development Reveals Divergent Expression Patterns from Other Teleosts

The regional identity of organs and organ systems along the anterior-posterior axis during embryonic development is patterned, in part, by Hox genes, which encode transcription factor proteins that activate or repress the expression of downstream target genes. Divergent nested Hox gene expression patterns may have had a role in facilitating morphological divergence of structures, such as the pharyngeal jaw apparatus, among evolutionarily divergent teleost fishes. Recent studies from several evolutionarily divergent teleosts, such as the Japanese Medaka (Oryzias latipes) and the Nile Tilapia (Oreochromis niloticus), have shown the presence of divergent expression patterns of several Hox genes within paralog groups 2–5 between these species. Specifically, these expression patterns were documented in the pharyngeal arches, which give rise to the pharyngeal jaw apparatus. While the expression patterns of several Zebrafish (Danio rerio) Hox genes that are orthologous to those of Medaka and Tilapia have been documented within the developing hindbrain and pharyngeal arches, many still have yet to be documented, especially within the pharyngeal arches during the postmigratory cranial neural crest cell stages. Here, we present the expression patterns of six Zebrafish Hox genes, hoxc3a, d3a, a4a, d4a, b5a, and c5a, within the pharyngeal arches during a postmigratory cranial neural crest cell stage and compare them to their orthologous genes of Medaka and Tilapia at similar stages. We show that while hoxc3a, d3a, and c5a of Zebrafish are absent from the pharyngeal arches, hoxa4a, d4a, and b5a show divergent expression patterns from their orthologs in Medaka and Tilapia. These observed divergences may be, in part, responsible for the divergent pharyngeal jaw apparatus structures exhibited by these fishes

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Background: The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag (R) system associated with the atmospheric generators for capnophilic bacteria Genbag CO2 (R) was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods: The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour H-3-hypoxanthine uptake inhibition method using the Genbag CO2 (R) system and compared to controlled incubator conditions (5% CO2 and 10% O-2). Results: The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O-2) were significantly higher than those of Genbag (R) conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine. To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag (R) conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O-2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM). Conclusions: The atmospheric generators for capnophilic bacteria Genbag CO2 (R) is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro microtest results for anti-malarial drugs and the importance of determining the microtest conditions before comparing and analysing the data from different laboratories and concluding on malaria resistance

An immunohistological study of testicular germ cell tumours using two different monoclonal antibodies against placental alkaline phosphatase.

Using two monoclonal antibodies directed against placental alkaline phosphatase (H17E2 and D20L) the immunohistological staining of testicular germ cell tumours was compared with that of a wide range of normal and malignant tissues. All seminomas and malignant teratomas tested gave strong positive labelling with H17E2 but were either negative or only patchily positive with D20L. Neither antibody gave any positive reaction on the normal tissues tested. All other malignancies were negative with both antibodies apart from two cases of ovarian and one case of endometrical cancer (strongly stained by H17E2) and three cases of colonic carcinoma (weakly and patchily stained by both H17E2 and D20L). This indicates that germ cell neoplasms generally express a form of placental alkaline phosphatase recognised by antibody H17E2