Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

Impact of deprivation and rural residence on treatment of colorectal and lung cancer

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

The variable functional effects of the pacing site in normal and scarred ventricles

The pacing site has been shown to influence functional improvement with cardiac resynchronization therapy. We evaluated the effects of the pacing site on left ventricular (LV) function in an animal model. Equilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with ventricular pacing, from three pacing sites in seven normal and eight infarcted dogs. QRS duration, electrical activation pattern, wall motion, LV ejection fraction (EF), synchrony of ventricular contraction, and mean arterial pressure (MAP), were related to the pacing site and infarct size, during each of 120 episodes. Little changed during pacing in normals. In infarcted dogs, LV wall motion, and synchrony worsened, LVEF and MAP often fell. These changes related to altered activation patterns which were influenced by the pacing site but were not related to infarct size. Hemodynamic and functional LV changes after infarction were found to vary with the pacing site and associated conduction and synchrony

Rasch model analysis of the Depression, Anxiety and Stress Scales (DASS)

<p>Abstract</p> <p>Background</p> <p>There is a growing awareness of the need for easily administered, psychometrically sound screening tools to identify individuals with elevated levels of psychological distress. Although support has been found for the psychometric properties of the Depression, Anxiety and Stress Scales (DASS) using classical test theory approaches it has not been subjected to Rasch analysis. The aim of this study was to use Rasch analysis to assess the psychometric properties of the DASS-21 scales, using two different administration modes.</p> <p>Methods</p> <p>The DASS-21 was administered to 420 participants with half the sample responding to a web-based version and the other half completing a traditional pencil-and-paper version. Conformity of DASS-21 scales to a Rasch partial credit model was assessed using the RUMM2020 software.</p> <p>Results</p> <p>To achieve adequate model fit it was necessary to remove one item from each of the DASS-21 subscales. The reduced scales showed adequate internal consistency reliability, unidimensionality and freedom from differential item functioning for sex, age and mode of administration. Analysis of all DASS-21 items combined did not support its use as a measure of general psychological distress. A scale combining the anxiety and stress items showed satisfactory fit to the Rasch model after removal of three items.</p> <p>Conclusion</p> <p>The results provide support for the measurement properties, internal consistency reliability, and unidimensionality of three slightly modified DASS-21 scales, across two different administration methods. The further use of Rasch analysis on the DASS-21 in larger and broader samples is recommended to confirm the findings of the current study.</p

RDR2 Partially Antagonizes the Production of RDR6-Dependent siRNA in Sense Transgene-Mediated PTGS

Background: RNA-DEPENDENT RNA POLYMERASE6 (RDR6) and SUPPRESSOR of GENE SILENCING 3 (SGS3) are required for DNA methylation and post-transcriptional gene silencing (PTGS) mediated by 21-nt siRNAs produced by sense transgenes (S-PTGS). In contrast, RDR2, but not RDR6, is required for DNA methylation and TGS mediated by 24-nt siRNAs, and for cellto-cell spreading of IR-PTGS mediated by 21-nt siRNAs produced by inverted repeat transgenes under the control of a phloem-specific promoter. Principal Findings: In this study, we examined the role of RDR2 and RDR6 in S-PTGS. Unlike RDR6, RDR2 is not required for DNA methylation of transgenes subjected to S-PTGS. RDR6 is essential for the production of siRNAs by transgenes subjected to S-PTGS, but RDR2 also contributes to the production of transgene siRNAs when RDR6 is present because rdr2 mutations reduce transgene siRNA accumulation. However, the siRNAs produced via RDR2 likely are counteractive in wildtype plants because impairement of RDR2 increases S-PTGS efficiency at a transgenic locus that triggers limited silencing, and accelerates S-PTGS at a transgenic locus that triggers efficient silencing. Conclusions/Significance: These results suggest that RDR2 and RDR6 compete for RNA substrates produced by transgenes subjected to S-PTGS. RDR2 partially antagonizes RDR6 because RDR2 action likely results in the production of counteractiv

Merged consensus clustering to assess and improve class discovery with microarray data

<p>Abstract</p> <p>Background</p> <p>One of the most commonly performed tasks when analysing high throughput gene expression data is to use clustering methods to classify the data into groups. There are a large number of methods available to perform clustering, but it is often unclear which method is best suited to the data and how to quantify the quality of the classifications produced.</p> <p>Results</p> <p>Here we describe an R package containing methods to analyse the consistency of clustering results from any number of different clustering methods using resampling statistics. These methods allow the identification of the the best supported clusters and additionally rank cluster members by their fidelity within the cluster. These metrics allow us to compare the performance of different clustering algorithms under different experimental conditions and to select those that produce the most reliable clustering structures. We show the application of this method to simulated data, canonical gene expression experiments and our own novel analysis of genes involved in the specification of the peripheral nervous system in the fruitfly, <it>Drosophila melanogaster</it>.</p> <p>Conclusions</p> <p>Our package enables users to apply the merged consensus clustering methodology conveniently within the R programming environment, providing both analysis and graphical display functions for exploring clustering approaches. It extends the basic principle of consensus clustering by allowing the merging of results between different methods to provide an averaged clustering robustness. We show that this extension is useful in correcting for the tendency of clustering algorithms to treat outliers differently within datasets. The R package, <it>clusterCons</it>, is freely available at CRAN and sourceforge under the GNU public licence.</p

Immunogenicity Is Not Improved by Increased Antigen Dose or Booster Dosing of Seasonal Influenza Vaccine in a Randomized Trial of HIV Infected Adults

The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 =  31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.ClinicalTrials.gov NCT00764998