Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined.
We completed a comprehensive literature ...search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed.
One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0–12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9–34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4–31.1. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01–16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ2 = 2.12, P = 0.5473).
The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.
Abstract
We present an HST/Advanced Camera for Surveys (ACS) weak gravitational lensing analysis of 13 massive high-redshift (zmedian = 0.88) galaxy clusters discovered in the South Pole Telescope ...(SPT) Sunyaev–Zel'dovich Survey. This study is part of a larger campaign that aims to robustly calibrate mass–observable scaling relations over a wide range in redshift to enable improved cosmological constraints from the SPT cluster sample. We introduce new strategies to ensure that systematics in the lensing analysis do not degrade constraints on cluster scaling relations significantly. First, we efficiently remove cluster members from the source sample by selecting very blue galaxies in V − I colour. Our estimate of the source redshift distribution is based on Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) data, where we carefully mimic the source selection criteria of the cluster fields. We apply a statistical correction for systematic photometric redshift errors as derived from Hubble Ultra Deep Field data and verified through spatial cross-correlations. We account for the impact of lensing magnification on the source redshift distribution, finding that this is particularly relevant for shallower surveys. Finally, we account for biases in the mass modelling caused by miscentring and uncertainties in the concentration–mass relation using simulations. In combination with temperature estimates from Chandra
we constrain the normalization of the mass–temperature scaling relation ln (E(z)M500c/1014 M⊙) = A + 1.5ln (kT/7.2 keV) to $A=1.81^{+0.24}_{-0.14}(\mathrm{stat.})\,{\pm }\,0.09(\mathrm{sys.})$, consistent with self-similar redshift evolution when compared to lower redshift samples. Additionally, the lensing data constrain the average concentration of the clusters to $c_\mathrm{200c}=5.6^{+3.7}_{-1.8}$.
Racial disparity has been investigated in a number of cancers; however, there remains a comparative paucity of data in Hodgkin's lymphoma (HL).
We examined time-, age-, and gender-specific incidence, ...disease characteristics, and survival across and within races for adolescent/adult HL (age 10–79 years) diagnosed during 1992–2007 in the SEER 13 registries.
A total of 15 662 HL cases were identified 11 211 non-Hispanic whites, 2067 Hispanics, 1662 blacks, and 722 Asian/Pacific Islanders (A/PI). Similar to whites, A/PIs had bimodal age-specific incidence, while blacks and Hispanics did not. Further, HL was significantly more common in Hispanics versus whites age >65 years (7.0/1 × 106 versus 4.5/1 × 106, respectively, P <0.01). By place of birth, US-born Hispanics and A/PIs age 20–39 years had higher incidence of HL versus their foreign-born counterparts (P <0.05), however, rates converged age >40 years. Interestingly, from 1992–1997 to 2003–2007, A/PI incidence rates increased >50% (P <0.001). Moreover, this increase was restricted to US-born A/PI. We also identified a number of disease-related differences based on race. Finally, 5-, 10-, and 15-year overall survival rates were inferior for blacks and Hispanics compared with whites (P <0.005 and P <0.001, respectively) and A/PI (P <0.018 and P <0.001, respectively). These differences persisted on multivariate analysis.
Collectively, we identified multiple racial disparities, including survival, in adolescent/adult HL.
Researchers have indicated that the collaborative problem‐solving space afforded by the collaborative systems significantly impact the problem‐solving process. However, recent investigations into ...collaborative simulations, which allow a group of students to jointly manipulate a problem in a shared problem space, have yielded divergent results regarding their effects on collaborative learning. Hence, this study analysed how students solved a physics problem using individual‐based and collaborative simulations to understand their effects on science learning. Multiple data sources including group discourse, problem‐solving activities, learning test scores, and questionnaire feedback were analysed. Lag sequential analysis on the data found that students using the two simulations collaborated with peers to solve the problem in significantly different patterns. The students using the collaborative simulations demonstrated active engagement in the collaborative activity; however, they did not transform discussions into workable problem‐solving activities. The students using the individual‐based simulation showed a lower level of collaboration engagement, starting with individual exploration of the problem with the simulation, followed by group reflection. The two groups also showed significant differences in their learning test scores. The findings and pedagogical suggestions are discussed in the hope of addressing critical activity design issues in using computer simulations for facilitating collaborative learning.
Lay Description
What is currently known about the subject matter?
Students tend to solve problems with simulations individually rather than collaboratively.
The free‐riding effect impedes student engagement in the collaborative process.
Collaborative simulations offer new affordances to better facilitate CPS processes.
What their paper adds to this?
Collaborative simulations strengthen interdependence and engagement in collaboration.
However, students did not show a significant enhancement in the learning tests.
They had difficulties transforming discussions into workable problem‐solving actions.
What the implications of study findings for practitioners?
Collaborative simulations can be applied to enhance collaborative engagement.
CPS activities should carefully leverage individual and collaborative learning.
Prompts that help students to closely relate their discussion to the simulation are needed.
Dislocations and their interactions strongly influence many material properties, ranging from the strength of metals and alloys to the efficiency of light-emitting diodes and laser diodes. Several ...experimental methods can be used to visualize dislocations. Transmission electron microscopy (TEM) has long been used to image dislocations in materials, and high-resolution electron microscopy can reveal dislocation core structures in high detail, particularly in annular dark-field mode. A TEM image, however, represents a two-dimensional projection of a three-dimensional (3D) object (although stereo TEM provides limited information about 3D dislocations). X-ray topography can image dislocations in three dimensions, but with reduced resolution. Using weak-beam dark-field TEM and scanning TEM, electron tomography has been used to image 3D dislocations at a resolution of about five nanometres (refs 15, 16). Atom probe tomography can offer higher-resolution 3D characterization of dislocations, but requires needle-shaped samples and can detect only about 60 per cent of the atoms in a sample. Here we report 3D imaging of dislocations in materials at atomic resolution by electron tomography. By applying 3D Fourier filtering together with equal-slope tomographic reconstruction, we observe nearly all the atoms in a multiply twinned platinum nanoparticle. We observed atomic steps at 3D twin boundaries and imaged the 3D core structure of edge and screw dislocations at atomic resolution. These dislocations and the atomic steps at the twin boundaries, which appear to be stress-relief mechanisms, are not visible in conventional two-dimensional projections. The ability to image 3D disordered structures such as dislocations at atomic resolution is expected to find applications in materials science, nanoscience, solid-state physics and chemistry.
Early-stage nasopharyngeal carcinoma (NPC) evades detection when the primary tumor is hidden from view on endoscopic examination. Therefore, in a prospective study of subjects being screened for NPC ...using plasma Epstein–Barr virus (EBV) DNA, we conducted a study to investigate whether magnetic resonance imaging (MRI) could detect endoscopically occult NPC.
Participants with persistently positive EBV DNA underwent endoscopic examination and biopsy when suspicious for NPC, followed by MRI blinded to the endoscopic findings. Participants with a negative endoscopic examination and positive MRI were recalled for biopsy or surveillance. Diagnostic performance was assessed by calculating sensitivity, specificity and accuracy, based on the histologic confirmation of NPC in the initial study or in a follow-up period of at least two years.
Endoscopic examination and MRI were performed on 275 participants, 34 had NPC, 2 had other cancers and 239 without cancer were followed-up for a median of 36months (24–60months). Sensitivity, specificity and accuracy were 76.5%, 97.5% and 94.9%, respectively, for endoscopic examination and 91.2%, 97.5% and 96.7%, respectively, for MRI. NPC was detected only by endoscopic examination in 1/34 (2.9%) participants (a participant with stage I disease), and only by MRI in 6/34 (17.6%) participants (stage I=4, II = 1, III = 1), two of whom had stage I disease and follow-up showing slow growth on MRI but no change on endoscopic examination for 36months.
MRI has a complementary role to play in NPC detection and can enable the earlier detection of endoscopically occult NPC.
Summary Objective This study aimed to characterize the in-situ mechanical property and morphology of individual collagen fibril in osteoarthritic cartilage using indentation-type atomic force ...microscopy (IT-AFM). Methods The specimens with intact articular cartilage (AC), mild to severe degenerated cartilage from osteoarthritis (OA) were collected with informed consent from the postmenopausal women who underwent hip or knee arthroplasty. The fresh specimens were cryo-sectioned by layers with 50 μm thick for each from the articular surface to calcified cartilage, and then processed for AFM imaging and nanoindentation test. For each layer, a total of 20 collagen fibrils were randomly selected for testing. AFM tips with the nominal radius less than 10 nm were employed for probing the individual collagen fibril, and the obtained cantilever deflection signal and displacement were recorded for calculating its elastic modulus. Results An intact AC exhibited a gradation in elastic modulus of collagen fibrils from articular surface (2.65 ± 0.31 GPa) to the cartilage–bone interface (3.70 ± 0.44 GPa). It was noted in mildly degenerated OA cartilage that the coefficient of variation for mechanical properties of collagen fibers, ranging from 25% to 48%, significantly increased as compared with intact one (12%). The stiffened collagen fibrils occurred at either articular surface (3.11 ± 0.91 GPa) or the cartilage–bone interface (5.64 ± 1.10 GPa), accompanied by loosely organized meshwork with advancement of OA cartilage degeneration. It was echoed by histological findings of OA cartilage, including fibrotic changes of surface region and tidemark irregularities. Conclusion The stiffened collagen fibrils in AC occurred with OA onset and progression, not only at articular surface but also the cartilage–bone interface.
Background and Aims: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular ...complications. Methods and Results: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hopsital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (χ2 = 3.99, p = 0.046) and third week (χ2 = 6.53, p = 0.01), although it could not explain tachycardia during follow up. Conclusions: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.
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