Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British ...Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.
The Jovian Auroral Distributions Experiment (JADE) on Juno provides the critical
in situ
measurements of electrons and ions needed to understand the plasma energy particles and processes that fill ...the Jovian magnetosphere and ultimately produce its strong aurora. JADE is an instrument suite that includes three essentially identical electron sensors (JADE-Es), a single ion sensor (JADE-I), and a highly capable Electronics Box (EBox) that resides in the Juno Radiation Vault and provides all necessary control, low and high voltages, and computing support for the four sensors. The three JADE-Es are arrayed 120
∘
apart around the Juno spacecraft to measure complete electron distributions from ∼0.1 to 100 keV and provide detailed electron pitch-angle distributions at a 1 s cadence, independent of spacecraft spin phase. JADE-I measures ions from ∼5 eV to ∼50 keV over an instantaneous field of view of 270
∘
×90
∘
in 4 s and makes observations over all directions in space each 30 s rotation of the Juno spacecraft. JADE-I also provides ion composition measurements from 1 to 50 amu with
m
/Δ
m
∼2.5, which is sufficient to separate the heavy and light ions, as well as O+ vs S+, in the Jovian magnetosphere. All four sensors were extensively tested and calibrated in specialized facilities, ensuring excellent on-orbit observations at Jupiter. This paper documents the JADE design, construction, calibration, and planned science operations, data processing, and data products. Finally, the
Appendix
describes the Southwest Research Institute SwRI electron calibration facility, which was developed and used for all JADE-E calibrations. Collectively, JADE provides remarkably broad and detailed measurements of the Jovian auroral region and magnetospheric plasmas, which will surely revolutionize our understanding of these important and complex regions.
Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma Schmitz, Roland; Wright, George W; Huang, Da Wei ...
New England journal of medicine/The New England journal of medicine,
04/2018, Letnik:
378, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like ABC, germinal-center ...B-cell-like GCB, and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics.
We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.
We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88
and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition.
We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).
Elastic strain engineering for ultralow mechanical dissipation Ghadimi, A H; Fedorov, S A; Engelsen, N J ...
Science (American Association for the Advancement of Science),
2018-May-18, 2018-05-18, 20180518, Letnik:
360, Številka:
6390
Journal Article
Recenzirano
Extreme stresses can be produced in nanoscale structures; this feature has been used to realize enhanced materials properties, such as the high mobility of silicon in modern transistors. We show how ...nanoscale stress can be used to realize exceptionally low mechanical dissipation when combined with "soft-clamping"-a form of phononic engineering. Specifically, using a nonuniform phononic crystal pattern, we colocalize the strain and flexural motion of a free-standing silicon nitride nanobeam. Ringdown measurements at room temperature reveal string-like vibrational modes with quality (
) factors as high as 800 million and
× frequency exceeding 10
hertz. These results illustrate a promising route for engineering ultracoherent nanomechanical devices.
PDF
