A refined, rapid and reproducible high resolution melt (HRM)-based method suitable for quantification of global LINE-1 repetitive element methylation

<p>Abstract</p> <p>Background</p> <p>The methylation of DNA is recognized as a key mechanism in the regulation of genomic stability and evidence for its role in the development of cancer is accumulating. LINE-1 methylation status represents a surrogate measure of genome-wide methylation.</p> <p>Findings</p> <p>Using high resolution melt (HRM) curve analysis technology, we have established an in-tube assay that is linear (r > 0.9986) with a high amplification efficiency (90-105%), capable of discriminating between partcipant samples with small differences in methylation, and suitable for quantifying a wide range of LINE-1 methylation levels (0-100%)--including the biologically relevant range of 50-90% expected in human DNA. We have optimized this procedure to perform using 2 μg of starting DNA and 2 ng of bisulfite-converted DNA for each PCR reaction. Intra- and inter-assay coefficients of variation were 1.44% and 0.49%, respectively, supporting the high reproducibility and precision of this approach.</p> <p>Conclusions</p> <p>In summary, this is a completely linear, quantitative HRM PCR method developed for the measurement of LINE-1 methylation. This cost-efficient, refined and reproducible assay can be performed using minimal amounts of starting DNA. These features make our assay suitable for high throughput analysis of multiple samples from large population-based studies.</p

The interplay between formal and informal elements in analysing situations of role conflict among construction participants

The interplay of formal and informal factors in construction teams influences the enactment of roles and the individuals who fulfil those roles. With a specific focus on a phenomenon called role conflict, the aim is to explore if and how the interaction of formal and informal elements would lead to situations of role conflict. This phenomenon proved to lead to frustration, tension and employee burnout. An analytical model of role interaction was developed, which disentangles formal and informal elements that shape role interactions. Qualitative data was collected through semi-structured interviews, project documents and observations. Four cases of role conflict are presented here. Contract, as a formal element, and participant’s values and interests, as informal elements, appeared to be the most important factor shaping participants’ expectations and behaviours. The analysis in this study showed that if a participant who faces role conflict is able to influence the formal elements in favour of his or her informal elements, then he or she may experience less frustration. At a more general level, the results suggest that increasing formality can increase participants’ frustration, which then would decrease the likelihood of collaboration. As the theoretical contribution, this research extends organizational role theory to deal with informal and formal aspects. Taking into account formal sources enables the study of how roles are institutionally governed while including informal sources allows for the idea that some of the aspects of the role, even in the context of work role, are socially constructed

Mortality due to cancer treatment delay: systematic review and meta-analysis.

OBJECTIVE: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Published studies in Medline from 1 January 2000 to 10 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. RESULTS: The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. CONCLUSIONS: Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes

Intermediate and extreme mass-ratio inspirals — astrophysics, science applications and detection using LISA

Black hole binaries with extreme (gtrsim104:1) or intermediate (~102–104:1) mass ratios are among the most interesting gravitational wave sources that are expected to be detected by the proposed laser interferometer space antenna (LISA). These sources have the potential to tell us much about astrophysics, but are also of unique importance for testing aspects of the general theory of relativity in the strong field regime. Here we discuss these sources from the perspectives of astrophysics, data analysis and applications to testing general relativity, providing both a description of the current state of knowledge and an outline of some of the outstanding questions that still need to be addressed. This review grew out of discussions at a workshop in September 2006 hosted by the Albert Einstein Institute in Golm, Germany

A prospective study of rural drinking water quality and acute gastrointestinal illness

BACKGROUND: This study examined the relationship between the bacteriological contamination of drinking water from private wells and acute gastrointestinal illness (AGII), using current government standards for safe drinking water. METHODS: A prospective cohort study was conducted using 235 households (647 individuals) randomly selected from four rural hamlets. Data were collected by means of a self-administered questionnaire, a self-report diary of symptoms and two drinking water samples. RESULTS: Twenty percent of households sampled, had indicator bacteria (total coliform or Escherichia coli (E. coli)) above the current Canadian and United States standards for safe drinking water. No statistically significant associations between indicator bacteria and AGII were observed. The odds ratio (OR) for individuals exposed to E. coli above the current standards was 1.52 (95% confidence interval (CI), 0.33–6.92), compared to individuals with levels below current standards. The odds ratio estimate for individuals exposed to total coliforms above the current standards was 0.39 (95% CI, 0.10–1.50). CONCLUSIONS: This study observed a high prevalence of bacteriological contamination of private wells in the rural hamlets studied. Individual exposure to contaminated water defined by current standards may be associated with an increased risk of AGII

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

Mass Segregation in Young Magellanic Clouds Star Clusters: Four Clusters observed with HST

We present the results of our investigation on the phenomenon of mass segregation in young star clusters in the Magellanic Clouds. HST/WFPC2 observations on NGC 1818, NGC 2004 & NGC 2100 in the Large Magellanic Cloud and NGC 330 in the Small Magellanic Cloud have been used for the application of diagnostic tools for mass segregation: i) the radial density profiles of the clusters for various mass groups and ii) their mass functions (MFs) at various radii around their centres. All four clusters are found to be mass segregated, but each one in a different manner. Specifically not all the clusters in the sample show the same dependence of their density profiles on the selected magnitude range, with NGC 1818 giving evidence of a strong such relation and NGC 330 showing only a hint of the phenomenon. NGC 2004 did not also show any significant signature of mass segregation in its density profiles. The MFs radial dependence provides clear proof of the phenomenon for NGC 1818, NGC 2100 and NGC 2004, while for NGC 330 it gives only indications. An investigation on the constraints introduced by the application of both diagnostic tools is presented. We also discuss the problems related to the construction of a reliable MF for a cluster and their impact on the investigation of the phenomenon of mass segregation. We find that the MFs of these clusters as they were constructed with two methods, are comparable to Salpeter's IMF. A discussion is given on the dynamical status of the clusters and a test is applied on the equipartition among several mass groups in them. Both showed that the observed mass segregation in the clusters is of primordial nature.Comment: A&A Accepted, 20 pages, 9 Figures, Version with language errors and typos correcte

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured