To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA).
All Assessment of SpondyloArthritis international Society (ASAS) members were ...invited to include consecutively new patients with chronic (> or =3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%.
Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having "non-radiographic" axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm") or the presence of HLA-B27 plus at least two SpA features ("clinical arm"). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%).
The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain.
NCT00328068.
We present sensitive 850 m imaging of the Cosmological Evolution Survey (COSMOS) field using 640 hr of new and archival observations taken with SCUBA-2 at the East Asian Observatory's James Clerk ...Maxwell Telescope. The SCUBA-2 COSMOS survey (S2COSMOS) achieves a median noise level of 850 m = 1.2 mJy beam−1 over an area of 1.6 sq. degree (main; Hubble Space Telescope/Advanced Camera for Surveys footprint), and 850 m = 1.7 mJy beam−1 over an additional 1 sq. degree of supplementary (supp) coverage. We present a catalog of 1020 and 127 sources detected at a significance level of >4 and >4.3 in the main and supp regions, respectively, corresponding to a uniform 2% false-detection rate. We construct the single-dish 850 m number counts at S850 > 2 mJy and show that these S2COSMOS counts are in agreement with previous single-dish surveys, demonstrating that degree-scale fields are sufficient to overcome the effects of cosmic variance in the S850 = 2-10 mJy population. To investigate the properties of the galaxies identified by S2COSMOS sources we measure the surface density of near-infrared-selected galaxies around their positions and identify an average excess of 2.0 0.2 galaxies within a 13″ radius (∼100 kpc at z ∼ 2). The bulk of these galaxies represent near-infrared-selected submillimeter galaxies and/or spatially correlated sources and lie at a median photometric redshift of z = 2.0 0.1. Finally, we perform a stacking analysis at submillimeter and far-infrared wavelengths of stellar-mass-selected galaxies (M = 1010-1012 M ) from z = 0-4, obtaining high-significance detections at 850 m in all subsets (signal-to-noise ratio, S/N = 4-30), and investigate the relation between far-infrared luminosity, stellar mass, and the peak wavelength of the dust spectral energy distribution. The publication of this survey adds a new deep, uniform submillimeter layer to the wavelength coverage of this well-studied COSMOS field.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
To compare three groupings of Electronic Health Record (EHR) billing codes for their ability to represent clinically meaningful phenotypes and to replicate known genetic associations. The three ...tested coding systems were the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, the Agency for Healthcare Research and Quality Clinical Classification Software for ICD-9-CM (CCS), and manually curated "phecodes" designed to facilitate phenome-wide association studies (PheWAS) in EHRs.
We selected 100 disease phenotypes and compared the ability of each coding system to accurately represent them without performing additional groupings. The 100 phenotypes included 25 randomly-chosen clinical phenotypes pursued in prior genome-wide association studies (GWAS) and another 75 common disease phenotypes mentioned across free-text problem lists from 189,289 individuals. We then evaluated the performance of each coding system to replicate known associations for 440 SNP-phenotype pairs.
Out of the 100 tested clinical phenotypes, phecodes exactly matched 83, compared to 53 for ICD-9-CM and 32 for CCS. ICD-9-CM codes were typically too detailed (requiring custom groupings) while CCS codes were often not granular enough. Among 440 tested known SNP-phenotype associations, use of phecodes replicated 153 SNP-phenotype pairs compared to 143 for ICD-9-CM and 139 for CCS. Phecodes also generally produced stronger odds ratios and lower p-values for known associations than ICD-9-CM and CCS. Finally, evaluation of several SNPs via PheWAS identified novel potential signals, some seen in only using the phecode approach. Among them, rs7318369 in PEPD was associated with gastrointestinal hemorrhage.
Our results suggest that the phecode groupings better align with clinical diseases mentioned in clinical practice or for genomic studies. ICD-9-CM, CCS, and phecode groupings all worked for PheWAS-type studies, though the phecode groupings produced superior results.
The Adaptive Poisson–Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that have provided impact in the study of a ...broad range of chemical, biological, and biomedical applications. APBS addresses the three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this article, we discuss the models and capabilities that have recently been implemented within the APBS software package including a Poisson–Boltzmann analytical and a semi‐analytical solver, an optimized boundary element solver, a geometry‐based geometric flow solvation model, a graph theory‐based algorithm for determining pKa values, and an improved web‐based visualization tool for viewing electrostatics.
Salinity is a fundamental property of watermasses that is useful in paleoenvironmental and paleoecological studies, yet the theory of application of geochemical proxies to paleosalinity ...reconstruction is underdeveloped. Here, we explore the use of three elemental ratios for paleosalinity reconstruction: boron/gallium (B/Ga), strontium/barium (Sr/Ba), and sulfur/total organic carbon (S/TOC) ratios. We compiled a large set of modern aqueous and sedimentary chemical data representing a range of salinity facies (i.e., freshwater, brackish, marine) in order to test the relationships of these proxies to ambient watermass salinity and to determine their viability for paleosalinity analysis. Sediment data were limited to fine-grained siliciclastic units (muds/shales/mudstones) without significant carbonate content, in which the elements of interest were mainly acquired through adsorption of dissolved species, forging a connection between elemental proxy values and watermass chemistry. In modern systems, watermass salinity is correlated with these proxies, yielding r of +0.99 and +0.76 for aqueous and sediment B/Ga, +0.66 and +0.54 for aqueous and sediment Sr/Ba, and +0.98 for aqueous sulfate and +0.66 for sediment S/TOC (all significant at p(α) < 0.01). These relationships establish the basis for use of these elemental ratios as paleosalinity proxies. Elemental crossplots permitted estimation of approximate salinity thresholds for each proxy: (1) B/Ga is <3 in freshwater, 3–6 in brackish, and >6 in marine facies; (2) Sr/Ba is <0.2 in freshwater, 0.2–0.5 in brackish, and >0.5 in marine facies; and (3) S/TOC is <0.1 in freshwater and >0.1 in brackish and marine facies. S/TOC did not discriminate effectively between brackish and marine facies, probably because microbial sulfate reduction (MSR) is generally Corg-limited rather than sulfate-limited in both facies. The accuracies of these thresholds for prediction of the salinity facies of sediments are ∼88% for B/Ga, ∼66% for Sr/Ba, and ∼91% for S/TOC. Although the Sr/Ba proxy is slightly less robust owing to difficulty in removing all carbonate Sr influence and/or to greater mobility of Sr and Ba in the burial environment, we strongly advocate use of multiple proxies in order to support paleosalinity interpretations. Finally, we illustrate the application of these proxies with case studies of (1) the Ordos Basin in North China, which contains Ordovician marine shales and Triassic terrestrial mudstones, and (2) the mid-Eocene Bohai Bay Basin in NE China, which accumulated brackish to marine mudstones.
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we ...conducted whole-genome CRISPR-Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance. Mechanistically, we show that C20orf196 and FAM35A form a complex, 'Shieldin' (SHLD1/2), with FAM35A interacting with single-stranded DNA through its C-terminal oligonucleotide/oligosaccharide-binding fold region. We establish that Shieldin acts as the downstream effector of 53BP1/RIF1/MAD2L2 to promote DNA double-strand break (DSB) end-joining by restricting DSB resection and to counteract homologous recombination by antagonizing BRCA2/RAD51 loading in BRCA1-deficient cells. Notably, Shieldin inactivation further sensitizes BRCA1-deficient cells to cisplatin, suggesting how defining the SHLD1/2 status of BRCA1-deficient tumours might aid patient stratification and yield new treatment opportunities. Highlighting this potential, we document reduced SHLD1/2 expression in human breast cancers displaying intrinsic or acquired PARP-inhibitor resistance.
The detection of GW170817 and its electromagnetic counterparts allows us to constrain the equation of state of dense matter in new and complementary ways. Very stiff equations of state are ruled out ...by the upper limit on the average tidal deformability, , imposed by the detected gravitational wave signal. A lower limit, , can also be extracted by considering the large amount of ejected matter that powers the kilonova AT2017gfo. By using several microscopic nucleonic equations of state, we first confirm the existence of a monotonic relation between R1.5 (the radius of the 1.5 M configuration) and . This translates the limits on into limits on the radius: 11.8 km R1.5 13.1 km. We then show that the monotonic relation is violated if a second branch of compact stars composed of quark matter exists, as in the two-families or twin-stars scenarios. In particular, it is possible to fulfill the limits on while having R1.5 significantly smaller than 12 km. In both of these scenarios, the event GW170817/AT2017gfo originates from the merger of a hadronic star and a star containing quark matter.
In this work, the electronic properties of phosphorene nanoribbons with different width and edge configurations are studied by using density functional theory. It is found that the armchair ...phosphorene nanoribbons are semiconducting while the zigzag nanoribbons are metallic. The band gaps of armchair nanoribbons decrease monotonically with increasing ribbon width. By passivating the edge phosphorus atoms with hydrogen, the zigzag series also become semiconducting, while the armchair series exhibit a larger band gap than their pristine counterpart. The electronic transport properties of these phosphorene nanoribbons are then investigated using Boltzmann theory and relaxation time approximation. We find that all the semiconducting nanoribbons exhibit very large values of Seebeck coefficient and can be further enhanced by hydrogen passivation at the edge. Taking pristine armchair nanoribbons and hydrogen-passivated zigzag naoribbons with width N = 7, 8, 9 as examples, we calculate the lattice thermal conductivity with the help of phonon Boltzmann transport equation and evaluate the width-dependent thermoelectric performance. Due to significantly enhanced Seebeck coefficient and decreased thermal conductivity, we find that at least one type of phosphorene nanoribbons can be optimized to exhibit very high figure of merit (ZT values) at room temperature, which suggests their appealing thermoelectric applications.
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