After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma ...Epstein–Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor–lymph node–metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy.
The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II–IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death.
Combining post-RT EBV DNA level (0, 1–49, 50–499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts.
Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.
•Integrating postradiotherapy plasma Epstein–Barr virus (EBV) DNA and tumor–lymph node–metastasis (TNM) stage improves the risk stratification of nasopharyngeal carcinoma.•Postradiotherapy plasma EBV DNA is a better predictor of early death in nasopharyngeal carcinoma than TNM stage.•The low-risk group by recursive partitioning model can spare more patients from unnecessary toxicity of adjuvant therapy.
Under the Every Student Succeeds Act, whole-school reforms will continue to be a prominent strategy for improving student outcomes in low-performing schools. As reform models have proliferated, so ...has research evaluating the impact in reform schools. However, previous evaluations have rarely examined unintended spillover effects in nonreform schools. With data from Tennessee, this study uses difference-in-differences models to estimate spillover effects from teachers who transfer when their school begins implementing turnaround reforms. Results show that teachers who transfer tend to be less effective than teachers who stay, and they tend to move into nearby schools that are themselves low-performing. However, after transferring, these teachers produce modest positive spillover effects on student test scores in nonreform schools, which is likely explained by improvements in their effectiveness. Moreover, I find that working with more effective peers is a likely mechanism to explain improved teacher effectiveness after they transfer. Overall, this study draws attention to the need for future educational policy evaluations that quantify both intended and unintended spillover effects.
We theoretically investigate high-pressure effects on the atomic dynamics of metallic glasses. The theory predicts compression-induced rejuvenation and the resulting strain hardening that have been ...recently observed in metallic glasses. Structural relaxation under pressure is mainly governed by local cage dynamics. The external pressure restricts the dynamical constraints and slows down the atomic mobility. In addition, the compression induces a rejuvenated metastable state (local minimum) at a higher energy in the free-energy landscape. Thus, compressed metallic glasses can rejuvenate and the corresponding relaxation is reversible. This behavior leads to strain hardening in mechanical deformation experiments. Theoretical predictions agree well with experiments.
A new methodology is presented for the conditioning of categorical multiple‐point statistics (MPS) simulations to dynamic data with an iterative ensemble smoother (ES‐MDA). The methodology relies on ...a novel multiresolution parameterization of the categorical MPS simulation. The ensemble of latent parameters is initially defined on the basis of the coarsest‐resolution simulations of an ensemble of multiresolution MPS simulations. Because this ensemble is non‐multi‐Gaussian, additional steps prior to the computation of the first update are proposed. In particular, the parameters are updated at predefined locations at the coarsest scale and integrated as hard data to generate a new multiresolution MPS simulation. The performance of the methodology was assessed on a synthetic groundwater flow problem inspired from a real situation. The results illustrate that the method converges towards a set of final categorical realizations that are consistent with the initial categorical ensemble. The convergence is reliable in the sense that it is fully controlled by the integration of the ES‐MDA update into the new conditional multiresolution MPS simulations. Thanks to a massively reduced number of parameters compared to the size of the categorical simulation, the identification of the geological structures during the data assimilation is particularly efficient for this example. The comparison between the estimated uncertainty and a reference estimate obtained with a Monte Carlo method shows that the uncertainty is not severely reduced during the assimilation as is often the case. The connectivity is successfully reproduced during the iterative procedure despite the rather large distance between the observation points.
Key Points
A novel multiresolution parameterization is used to condition categorical multiple‐point direct sampling simulations to dynamic data
Dynamic data are assimilated with an iterative ensemble smoother by updating continuous latent variables at the coarsest resolution
A robust convergence towards consistent geological structures and a good data match is illustrated on a synthetic groundwater flow problem
AbstractIn this paper, a group of demountable shear connectors have been developed and tested to assess their potential and suitability in terms of replacing welded shear studs. The experiments ...showed that these demountable shear connectors can be easily demounted after testing and have similar capacity and behavior to those of welded shear connectors. After the numerical simulation method had been validated against experimental observation, a parametric study was carried out to understand the effect of concrete grades and stud collar sizes on the shear resistance of demountable shear connections. Simple design calculation methods for welded shear connections or anchoring connections provided in European and American standards were checked to the suitability for assessment of this headed demountable shear connector.
We provide the first observational constraints on the sizes of the faintest galaxies lensed by the Hubble Frontier Fields (HFF) clusters. Ionizing radiation from faint galaxies likely drives cosmic ...reionization, and the HFF initiative provides a key opportunity to find such galaxies. However, we cannot assess their ionizing emissivity without a robust measurement of their sizes, since this is key to quantifying both their prevalence and the faint-end slope to the UV luminosity function. Here we provide the first size constraints with two new techniques. The first utilizes the fact that the detectability of highly magnified galaxies as a function of shear is very dependent on a galaxy's size. Only the most compact galaxies remain detectable in high-shear regions (versus a larger detectable size range for low shear), a phenomenon we quantify using simulations. Remarkably, however, no correlation is found between the surface density of faint galaxies and the predicted shear, using 87 high-magnification ( -100) -8 galaxies seen behind the first four HFF clusters. This can only be the case if faint ( mag) galaxies have significantly smaller sizes than more luminous galaxies, i.e., mas or 160-240 pc. As a second size probe, we rotate and stack 26 faint high-magnification sources along the major shear axis. Less elongation is found even for objects with an intrinsic half-light radius of 10 mas. Together, these results indicate that extremely faint -8 galaxies have near point-source profiles (half-light radii <30 mas and perhaps 5-10 mas). These results suggest smaller completeness corrections and hence shallower faint-end slopes for the -8 LFs than derived in some recent studies (by -0.3).
In a Federated Learning (FL) setup, a number of devices contribute to the training of a common model. We present a method for selecting the devices that provide updates in order to achieve improved ...generalization, fast convergence, and better device-level performance. We formulate a min-max optimization problem and decompose it into a primal-dual setup, where the duality gap is used to quantify the device-level performance. Our strategy combines exploration of data freshness through a random device selection with exploitation through simplified estimates of device contributions. This improves the performance of the trained model both in terms of generalization and personalization. A modified Truncated Monte-Carlo (TMC) method is applied during the exploitation phase to estimate the device's contribution and lower the communication overhead. The experimental results show that the proposed approach has a competitive performance, with lower communication overhead and competitive personalization performance against the baseline schemes.
Mixed results from evaluations of school reform suggest a need for evidence to explain why some models succeed while others fail. Addressing that need, this study uses structural equation modeling to ...estimate difference-in-differences models that examine mediating mechanisms for positive effects produced by Innovation Zone (iZone) reforms in Memphis, Tennessee. I find that iZone schools increased peer collaboration between teachers, which resulted in improved student achievement. Also, recruiting effective teachers led to a more positive learning environment and ultimately to improved student achievement. These results highlight peer collaboration, a positive learning environment, and the recruitment of effective educators as important practices that will likely facilitate improved school performance under future school reform plans.
Conventional strain-based mechanics theory does not account for contributions from strain gradients. Failure to include strain gradient contributions can lead to underestimates of stresses and ...size-dependent behaviors in small-scale structures. In this paper, a new set of higher-order metrics is developed to characterize strain gradient behaviors. This set enables the application of the higher-order equilibrium conditions to strain gradient elasticity theory and reduces the number of independent elastic length scale parameters from five to three. On the basis of this new strain gradient theory, a strain gradient elastic bending theory for plane-strain beams is developed. Solutions for cantilever bending with a moment and line force applied at the free end are constructed based on the new higher-order bending theory. In classical bending theory, the normalized bending rigidity is independent of the length and thickness of the beam. In the solutions developed from the higher-order bending theory, the normalized higher-order bending rigidity has a new dependence on the thickness of the beam and on a higher-order bending parameter,
b
h. To determine the significance of the size dependence, we fabricated micron-sized beams and conducted bending tests using a nanoindenter. We found that the normalized beam rigidity exhibited an inverse squared dependence on the beam's thickness as predicted by the strain gradient elastic bending theory, and that the higher-order bending parameter,
b
h, is on the micron-scale. Potential errors from the experiments, model and fabrication were estimated and determined to be small relative to the observed increase in beam's bending rigidity. The present results indicate that the elastic strain gradient effect is significant in elastic deformation of small-scale structures.
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