Momentum Cleaning in the CERN LHC

This paper describes the optimization of the optics and the collimator geometry for the momentum cleaning insertion of the LHC. To collimate the off-momentum secondary halo without disturbing the circ ulating beam, the normalized dispersion in IR3 is made as large as in the arcs. The jaw locations and orientations are numerically optimized to reduce the momentum-dependent halo amplitude. The second ary halo is kept within the available aperture for momentum deviations up to 0.44%, where the horizontal aperture is 4$\sigma\, compared to 12$\sigma\ on-momentum

G4 Resolvase 1 tightly binds and unwinds unimolecular G4-DNA

It has been previously shown that the DHX36 gene product, G4R1/RHAU, tightly binds tetramolecular G4-DNA with high affinity and resolves these structures into single strands. Here, we test the ability of G4R1/RHAU to bind and unwind unimolecular G4-DNA. Gel mobility shift assays were used to measure the binding affinity of G4R1/RHAU for unimolecular G4-DNA-formed sequences from the Zic1 gene and the c-Myc promoter. Extremely tight binding produced apparent Kd's of 6, 3 and 4 pM for two Zic1 G4-DNAs and a c-Myc G4-DNA, respectively. The low enzyme concentrations required for measuring these Kd's limit the precision of their determination to upper boundary estimates. Similar tight binding was not observed in control non-G4 forming DNA sequences or in single-stranded DNA having guanine-rich runs capable of forming tetramolecular G4-DNA. Using a peptide nucleic acid (PNA) trap assay, we show that G4R1/RHAU catalyzes unwinding of unimolecular Zic1 G4-DNA into an unstructured state capable of hybridizing to a complementary PNA. Binding was independent of adenosine triphosphate (ATP), but the PNA trap assay showed that unwinding of G4-DNA was ATP dependent. Competition studies indicated that unimolecular Zic1 and c-Myc G4-DNA structures inhibit G4R1/RHAU-catalyzed resolution of tetramolecular G4-DNA. This report provides evidence that G4R1/RHAU tightly binds and unwinds unimolecular G4-DNA structure

Machine studies during beam commissioning of the SPS-to-LHC transfer lines

Through May to September 2008, further beam commissioning of the SPS-to-LHC transfer lines was performed. For the first time, optics and dispersion measurements were also taken in the last part of the lines, and into the LHC. Extensive trajectory and optics studies were conducted, in parallel with hardware checks. In particular dispersion measurements and their comparison with the beam line model were analysed in detail and led to propose the addition of a dispersion-free steering algorithm in the existing trajectory correction program. Its effectiveness was simulated and is briefly discussed

Effectiveness of the Assessment of Burden of Chronic Obstructive Pulmonary Disease (ABC) tool: Study protocol of a cluster randomised trial in primary and secondary care

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a growing worldwide problem that imposes a great burden on the daily life of patients. Since there is no cure, the goal of treating COPD is to maintain or improve quality of life. We have developed a new tool, the Assessment of Burden of COPD (ABC) tool, to assess and visualize the integrated health status of patients with COPD, and to provide patients and healthcare providers with a treatment algorithm. This tool may be used during consultations to monitor the burden of COPD and to adjust treatment if necessary. The aim of the current study is to analyse the effectiveness of the ABC tool compared with usual care on health related quality of life among COPD patients over a period of 18 months. Methods/Design A cluster randomised controlled trial will be conducted in COPD patients in both primary and secondary care throughout the Netherlands. An intervention group, receiving care based on the ABC tool, will be compared with a control group receiving usual care. The primary outcome will be the change in score on a disease-specific-quality-of-life questionnaire, the Saint George Respiratory Questionnaire. Secondary outcomes will be a different questionnaire (the COPD Assessment Test), lung function and number of exacerbations. During the 18 months follow-up, seven measurements will be conducted, including a baseline and final measurement. Patients will receive questionnaires to be completed at home. Additional data, such as number of exacerbations, will be recorded by the patients’ healthcare providers. A total of 360 patients will be recruited by 40 general practitioners and 20 pulmonologists. Additionally, a process evaluation will be performed among patients and healthcare providers. Discussion The new ABC tool complies with the 2014 Global Initiative for Chronic Obstructive Lung Disease guidelines, which describe the necessity to classify patients on both their airway obstruction and a comprehensive symptom assessment. It has been developed to classify patients, but also to provide visual insight into the burden of COPD and to provide treatment advice. Trial registration Netherlands Trial Register, NTR3788

Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

BACKGROUND:The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient's distribution in relation to the questionnaire used. METHODS:136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. RESULTS:GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. CONCLUSIONS:Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01388218

First translational consensus on terminology and definitions of colonic motility in animals and humans studied by manometric and other techniques

Alterations in colonic motility are implicated in the pathophysiology of bowel disorders, but high-resolution manometry of human colonic motor function has revealed that our knowledge of normal motor patterns is limited. Furthermore, various terminologies and definitions have been used to describe colonic motor patterns in children, adults and animals. An example is the distinction between the high-amplitude propagating contractions in humans and giant contractions in animals. Harmonized terminology and definitions are required that are applicable to the study of colonic motility performed by basic scientists and clinicians, as well as adult and paediatric gastroenterologists. As clinical studies increasingly require adequate animal models to develop and test new therapies, there is a need for rational use of terminology to describe those motor patterns that are equivalent between animals and humans. This Consensus Statement provides the first harmonized interpretation of commonly used terminology to describe colonic motor function and delineates possible similarities between motor patterns observed in animal models and humans in vitro (ex vivo) and in vivo. The consolidated terminology can be an impetus for new research that will considerably improve our understanding of colonic motor function and will facilitate the development and testing of new therapies for colonic motility disorders. This Consensus Statement provides a conceptual and methodological framework to expand research on colonic motility in experimental animals and humans. The work is intended to facilitate the development of new drugs for common colonic motility disorders and of appropriate diagnostic and therapeutic algorithms for the management of paediatric and adult patients