A 20 kA Test Bench for High-Precision Current Measurements

The d.c. currents in the LHC dipole and quadrupole chains will require settings and adjustments with a precision of a few ppm. For an ultimate current level of 13 kA this represents an unprecedented accuracy. Compared to the requirements of previous accelerators at CERN, such as the LEP, this is a factor of ten better in accuracy at more than twice the current. State-of-the-art, zero-flux current transducers from Industry will be used for the precision measurements. As no existing laboratory would be capable of performing the calibrations of these transducers to the required precision, a major upgrading of the current Standards laboratory at CERN was decided. The paper describes the various phases of the project, from field calculations and design to construction and final commissioning of this unique test bench. The highly automated facility allows determination of off-sets, linearity and drift of transducers up to 20 kA but provides equally the means to study the sensitivity of the transducers to external stray fields as generated by currents in adjacent busbars

Understanding the theoretical underpinning of the exercise component in a fall prevention programme for older adults with mild dementia: a realist review protocol

Background Older adults with mild dementia are at an increased risk of falls. Preventing those at risk from falling requires complex interventions involving patient-tailored strength- and balance-challenging exercises, home hazard assessment, visual impairment correction, medical assessment and multifactorial combinations. Evidence for these interventions in older adults with mild cognitive problems is sparse and not as conclusive as the evidence for the general community-dwelling older population. The objectives of this realist review are (i) to identify the underlying programme theory of strength and balance exercise interventions targeted at those individuals that have been identified as falling and who have a mild dementia and (ii) to explore how and why that intervention reduces falls in that population, particularly in the context of a community setting. This protocol will explain the rationale for using a realist review approach and outline the method. Methods A realist review is a methodology that extends the scope of a traditional narrative or systematic evidence review. Increasingly used in the evaluation of complex interventions, a realist enquiry can look at the wider context of the intervention, seeking more to explain than judge if the intervention is effective by investigating why, what the underlying mechanism is and the necessary conditions for success. In this review, key rough programme theories were articulated and defined through discussion with a stakeholder group. The six rough programme theories outlined within this protocol will be tested against the literature found using the described comprehensive search strategy. The process of data extraction, appraisal and synthesis is outlined and will lead to the production of an explanatory programme theory. Discussion As far as the authors are aware, this is the first realist literature review within fall prevention research and adds to the growing use of this methodology within healthcare. This synthesis of evidence will provide a valuable addition to the evidence base surrounding the exercise component of a fall intervention programme for older adults with mild dementia and will ultimately provide clinically relevant recommendations for improving the care of people with dementia

Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

Background: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. Methods: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Results: Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. Conclusion: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM

Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-04989-w, published online 13 September 2018

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight