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A multiscale model is developed to investigate the evolution mechanisms of site-specific grain structures during additive manufacturing (AM) of metallic alloys, using the selective ...electron beam melting (SEBM) fabrication of Ti-6Al-4V as an example. Specifically, finite-element method is utilized to predict the thermal response at macroscale during SEBM, and the extracted thermal information is then input into a temperature-dependent phase-field model to simulate the grain growth at mesoscale. The grain epitaxial growth, grain selection, grain nucleation and layer-by-layer manufacturing fashion are incorporated, in order to accurately predict grain structure development and relevant physical processes during AM. It is found that, the development of the predominant grain structures in the thick and thin walls, i.e., the large vertical columnar β//Nz grains and slanted columnar grains with various grain orientations, respectively, can be attributed to the competition and collaboration between the thermal gradient and the crystallographically preferred grain growth, as shown from the different growth stages in the simulations. Good agreements in the final grain structures and textures are achieved between the experimental observations and numerical simulations. The present study potentially offers valuable insights and guidance toward designing AM conditions to tailor the grain structures and textures.
A fast Fourier transform (FFT) based computational approach integrating phase-field method (PFM) and crystal plasticity (CP) is proposed to model recrystallization of plastically deformed ...polycrystals in three dimensions (3-D). CP at the grain level is employed as the constitutive description to predict the inhomogeneous distribution of strain and stress fields after plastic deformation of a polycrystalline aggregate while the kinetics of recrystallization is obtained employing a PFM in the plastically deformed grain structure. The elasto-viscoplastic equilibrium is guaranteed during each step of temporal phase-field evolution. Static recrystallization involving plasticity during grain growth is employed as an example to demonstrate the proposed computational framework. The simulated recrystallization kinetics is compared using the classical Johnson–Mehl–Avrami–Kolmogorov (JMAK) theory. This study also gives us a new computational pathway to explore the plasticity-driven evolution of 3D microstructures.
Background
This study evaluated the prescribing trends of four commonly prescribed strong opioids in primary care and explored utilization in non‐cancer and cancer users.
Methods
This cross‐sectional ...study was conducted from 2000 to 2010 using the UK Clinical Practice Research Datalink. Prescriptions of buprenorphine, fentanyl, morphine and oxycodone issued to adult patients were included in this study. Opioid prescriptions issued after patients had cancer medical codes were defined as cancer‐related use; otherwise, they were considered non‐cancer use. Annual number of prescriptions and patients, defined daily dose (DDD/1000 inhabitants/day) and oral morphine equivalent (OMEQ) dose were measured in repeat cross‐sectional estimates.
Results
In total, there were 2,672,022 prescriptions (87.8% for non‐cancer) of strong opioids for 178,692 users (59.9% female, 83.9% non‐cancer, mean age 67.1 ± 17.0 years) during the study period. The mean annual (DDD/1000 inhabitants/day) was higher in the non‐cancer group than in the cancer group for all four opioids; morphine (0.73 ± 0.28 vs. 0.12 ± 0.04), fentanyl (0.46 ± 0.29 vs. 0.06 ± 0.24), oxycodone (0.24 ± 0.19 vs. 0.038 ± 0.028) and buprenorphine (0.23 ± 0.15 vs. 0.008 ± 0.006). The highest proportion of patients were prescribed low opioid doses (OMEQ ≤ 50 mg/day) in both non‐cancer (50.3%) and cancer (39.9%) groups, followed by the dose ranks of 51–100 mg/day (26.2% vs. 28.7%), 101–200 mg/day (15.1% vs. 19.2%) and >200 mg/day (8.25% vs. 12.1%).
Conclusions
There has been a huge increase in strong opioid prescribing in the United Kingdom, with the majority of prescriptions for non‐cancer pain. Morphine was the most frequently prescribed, but the utilization of oxycodone, buprenorphine and fentanyl increased markedly over time.
The enhancement of the functional properties of materials at reduced dimensions is crucial for continuous advancements in nanoelectronic applications. Here, we report that the scale reduction leads ...to the emergence of an important functional property, ferroelectricity, challenging the long-standing notion that ferroelectricity is inevitably suppressed at the scale of a few nanometers. A combination of theoretical calculations, electrical measurements, and structural analyses provides evidence of room-temperature ferroelectricity in strain-free epitaxial nanometer-thick films of otherwise nonferroelectric strontium titanate (SrTiO3). We show that electrically induced alignment of naturally existing polar nanoregions is responsible for the appearance of a stable net ferroelectric polarization in these films. This finding can be useful for the development of low-dimensional material systems with enhanced functional properties relevant to emerging nanoelectronic devices.
Objectives
To explore the association between orthostatic hypotension (OH) and frailty for hospitalized older patients and their vulnerable subgroups.
Design
A prospective, observational ...cross-sectional study.
Participants
693 older patients admitted to a geriatric evaluation and management unit.
Measurements
Barthel Index, Lawton’s instrumental activities of daily living, clinical frailty scale, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, and polypharmacy.
Results
Overall, the prevalence of OH and frailty was 26% and 36%, respectively. Subjects with OH were older, thinner, more commonly to have weakness, slowness, poorer physical function and higher levels of frailty. The prevalence of OH was substantially increased as higher levels of CFS (p for trend <0.001). Multivariate logistic regression showed significant association between OH and frailty (OR: 1.8, 95% CI: 1.2-2.7), but the association attenuated after adjustment for physical function. (OR: 1.4, 95% CI: 0.7-2.6). Nevertheless, associations between OH and frailty remained significant among vulnerable subgroups like women, subjects having weakness, slowness, poor cognitive function, polypharmacy or any IADL limitation.
Conclusions
OH in hospitalized older patients was associated with frailty and multiple complex care needs, especially in the vulnerable subgroups. Further study is needed to clarify the roles of OH in clinical practice.
Broad Learning System (BLS) that aims to offer an alternative way of learning in deep structure is proposed in this paper. Deep structure and learning suffer from a time-consuming training process ...because of a large number of connecting parameters in filters and layers. Moreover, it encounters a complete retraining process if the structure is not sufficient to model the system. The BLS is established in the form of a flat network, where the original inputs are transferred and placed as "mapped features" in feature nodes and the structure is expanded in wide sense in the "enhancement nodes." The incremental learning algorithms are developed for fast remodeling in broad expansion without a retraining process if the network deems to be expanded. Two incremental learning algorithms are given for both the increment of the feature nodes (or filters in deep structure) and the increment of the enhancement nodes. The designed model and algorithms are very versatile for selecting a model rapidly. In addition, another incremental learning is developed for a system that has been modeled encounters a new incoming input. Specifically, the system can be remodeled in an incremental way without the entire retraining from the beginning. Satisfactory result for model reduction using singular value decomposition is conducted to simplify the final structure. Compared with existing deep neural networks, experimental results on the Modified National Institute of Standards and Technology database and NYU NORB object recognition dataset benchmark data demonstrate the effectiveness of the proposed BLS.
Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the ...therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.
Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.
Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0–78.2) with nivolumab plus SOX and 76.5% (50.1–93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8–NR) and 10.6 months (5.6–12.5), respectively.
Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.
NCT02746796.
This paper presents Magnetospheric Multiscale mission (MMS) observations of the exhaust region in the vicinity of the central reconnection site in Earth's magnetopause current sheet. ...High-time-resolution measurements of field and particle distributions enable us to explore the fine structure of the diffusion region near the X line. Ions are decoupled from the magnetic field throughout the entire current sheet crossing. Electron jets flow downstream from the X line at speeds greater than the E by B drift velocity. At or around the magnetospheric separatrix, large-amplitude electric fields containing field-aligned components accelerate electrons along the magnetic field toward the X line. Near the neutral sheet, crescent-shaped electron distributions appear coincident with (1) an out-of-plane electric field whose polarity is opposite to that of the reconnection electric field and (2) the energy transfer from bulk kinetic to field energy. The observations indicate that MMS passed through the edge of an elongated electron diffusion region (EDR) or the outer EDR in the exhaust region.
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