Rapid reviews and the methodological rigor of evidence synthesis: a JBI position statement

The demand for rapid reviews has exploded in recent years. A rapid review is an approach to evidence synthesis that provides timely information to decision-makers (eg, health care planners, providers, policymakers, patients) by simplifying the evidence synthesis process. A rapid review is particularly appealing for urgent decisions. JBI is a world-renowned international collaboration for evidence synthesis and implementation methodologies. The principles for JBI evidence synthesis include comprehensiveness, rigor, transparency, and a focus on applicability to clinical practice. As such, JBI has not yet endorsed a specific approach for rapid reviews. In this paper, we compare rapid reviews versus other types of evidence synthesis, provide a range of rapid evidence products, outline how to appraise the quality of rapid reviews, and present the JBI position on rapid reviews. JBI Collaborating Centers conduct rapid reviews for decision-makers in specific circumstances, such as limited time or funding constraints. A standardized approach is not used for these cases;instead, the evidence synthesis methods are tailored to the needs of the decision-maker. The urgent need to deliver timely evidence to decision-makers poses challenges to JBI's mission to produce high-quality, trustworthy evidence. However, JBI recognizes the value of rapid reviews as part of the evidence synthesis ecosystem. As such, it is recommended that rapid reviews be conducted with the same methodological rigor and transparency expected of JBI reviews. Most importantly, transparency is essential, and the rapid review should clearly report where any simplification in the steps of the evidence synthesis process has been taken

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Poloidal OHMIC heating in a multipole

The feasibility of using poloidal currents to heat plasmas confined by a multipole field has been examined experimentaly in Tokapole II. The machine is operated as a toroidal octupole, with a time-varying toroidal magnetic field driving poloidal plasma currents I/sub plasma/ - 20 kA to give densities n/sub e/ - 10/sup 13/ cm/sup -3/ and temperatures T/sub e/ - 30 eV

A simple, low-cost, versatile CCD spectrometer for plasma spectroscopy

The authors have constructed a simple, low-cost CCD spectrometer capable of both high resolution ({Delta}{lambda} {le} 0.015 nm) and large bandpass (110 nm with {Delta}{lambda} {approximately}0.3 nm). These two modes of operation provide two broad areas of capability for plasma spectroscopy. The first major application is measurement of emission line broadening; the second is emission line surveys from the ultraviolet to the near infrared. Measurements have been made on a low-temperature plasma produced by a miniature electrostatic plasma source and the high-temperature plasma in the MST Reversed-Field Pinch. The spectrometer is a modified Jarrell-Ash 0.5 m Ebert-Fastie monochromator. Light is coupled into the entrance slit with a fused silica fiber optic bundle. The exposure time (2 ms minimum) is controlled by a fast electromechanical shutter. The exit plane detector is a compact and robust CCD detector developed for amateur astronomy by Santa Barbara Instrument Group. The CCD detector is controlled and read out by a Macintosh{reg_sign} computer. This spectrometer is sophisticated enough to serve well in a research laboratory, yet is simple and inexpensive enough to be affordable for instructional use

Experimental observation of plasma paramagnetism in a tokamak

The increase in the toroidal magnetic field of a tokamak due to plasma presence is measured experimentally and compared with predictions of an equilibrium code