UK Housing Market: Time Series Processes with Independent and Identically Distributed Residuals

The paper examines whether a univariate data generating process can be identified which explains the data by having residuals that are independent and identically distributed, as verified by the BDS test. The stationary first differenced natural log quarterly house price index is regressed, initially with a constant variance and then with a conditional variance. The only regression function that produces independent and identically distributed standardised residuals is a mean process based on a pure random walk format with Exponential GARCH in mean for the conditional variance. There is an indication of an asymmetric volatility feedback effect but higher frequency data is required to confirm this. There could be scope for forecasting the index but this is tempered by the reduction in the power of the BDS test if there is a non-linear conditional variance process

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The effect of mass administration of sulfadoxine-pyrimethamine combined with artesunate on malaria incidence: a double-blind, community-randomized, placebo-controlled trial in The Gambia.

A double-blind, community-randomized, placebo-controlled trial was conducted in a rural area of The Gambia between June and December 1999 to test whether a reduction in the infectious reservoir can reduce malaria transmission. Overall 14,017 (85%) individuals living in the study area were treated with either placebo or sulfadoxine-pyrimethamine (SP) combined with a single dose of artesunate (AS). Following the mass drug administration (MDA) 1375 children aged 6 months to 10 years were kept under surveillance for clinical malaria in 18 villages throughout the 1999 malaria transmission season. During a 20-week surveillance period 637 episodes of malaria were detected. The mean incidence rate was 2.5/100 child-weeks in the placebo villages, and 2.3/100 child-weeks in villages that received SP + AS. The mean rate ratio, adjusted for individual and village-level covariates, was 0.91 (95% CI 0.68-1.22, P = 0.49). During the first 2 months of surveillance, the malaria incidence was lower in treated villages. After 2 months the incidence was slightly higher in the MDA group but this was not statistically significant. Overall, no benefit of the MDA could be detected. The reason for the absence of an impact on malaria transmission is probably the very high basic reproductive number of malaria, and the persistence of mature gametocytes, which are not affected by AS treatment

Non-Replicating <i>Mycobacterium tuberculosis</i> Elicits a Reduced Infectivity Profile with Corresponding Modifications to the Cell Wall and Extracellular Matrix

<div><p>A key feature of <i>Mycobacterium tuberculosis</i> is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by <i>M. tuberculosis</i> in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) <i>M. tuberculosis</i> was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to <i>M. tuberculosis</i> dormancy and how this organism could be establishing latent disease.</p></div

Genes up-regulated in late stationary phase and during chronic infection in mice.

<p>Genes up-regulated in late stationary phase in Cultures 1 and 2 of <i>M. tuberculosis</i> and at 60 days post-infection in the BALB/C mice <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087329#pone.0087329-Talaat1" target="_blank">[22]</a>. The cluster profiles for the genes listed can be found in the supporting data at <a href="http://xenakis.mrc-bsu.cam.ac.uk/wernisch/enrichment/html/" target="_blank">http://xenakis.mrc-bsu.cam.ac.uk/wernisch/enrichment/html/</a>.</p

Gene expression clusters with a marked enrichment in fatty acid metabolism, lipid degradation, and cell wall re-modeling.

<p>Graphs show normalised log expression values (centered around a mean value of zero) over the time-courses in Cultures 1 and 2. The shaded area represents the 99% confidence interval for the curves.</p

Scanning electron micrograph images of formaldehyde-fixed cells sampled from Culture 2.

<p>Panel A) exponential phase at day 8; Panel B) stationary phase at day 44; Panel C) late stationary phase at day 107; and Panel D) NRP at day 292.</p

Histopathological changes in guinea pig lung following aerosol challenge with <i>M. tuberculosis</i> cultured from different growth phases of nutrient starvation at days 16 and 42 post challenge.

<p>H&E. Magnification bar, 500 µm.</p