•It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19).•We found that diabetes was associated with an approximately ...4-fold increased risk of having severe/critical COVID-19 illness.•This association was independent of age, sex, obesity, hypertension and smoking.•These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present our study on the spatially resolved H and M* relation for 536 star-forming and 424 quiescent galaxies taken from the MaNGA survey. We show that the star formation rate surface density ( ), ...derived based on the H emissions, is strongly correlated with the M* surface density ( ) on kiloparsec scales for star-forming galaxies and can be directly connected to the global star-forming sequence. This suggests that the global main sequence may be a consequence of a more fundamental relation on small scales. On the other hand, our result suggests that ∼20% of quiescent galaxies in our sample still have star formation activities in the outer region with lower specific star formation rate (SSFR) than typical star-forming galaxies. Meanwhile, we also find a tight correlation between and for LI(N)ER regions, named the resolved "LI(N)ER" sequence, in quiescent galaxies, which is consistent with the scenario that LI(N)ER emissions are primarily powered by the hot, evolved stars as suggested in the literature.
In practical engineering, cyclic shear stresses induced by earthquakes, traffic, and waves are superimposed on the initial static shear stress in sand fills or deposits, leading to complex responses ...of soils such as their deformation characteristics, pore pressure generation, and susceptibility (or cyclic resistance) to liquefaction. To experimentally investigate the undrained cyclic response of saturated sand, a series of triaxial tests were performed, covering a broad range of initial static and cyclic deviatoric stress levels. The results indicate that different stress conditions lead to two types of cyclic behavior: cyclic mobility and residual deformation accumulation. The compressional static stress is beneficial to the cyclic resistance of the dense sand, whereas the extensional static stress is regarded as detrimental as it tended to reduce the cyclic strength. Moreover, by comparing the available test data obtained from the same sand with varying initial densities and confining pressures, the static shear effect on cyclic resistance was found to be dependent on the state of the sand. Compared to the interpretation made using the limiting pore pressure-based criterion, the conventional failure criterion using a cyclic axial strain of 5% may lead to a substantial overestimation of the cyclic resistance, thus resulting in unsafe assessment and design. Hence, by employing the pore pressure criterion, the pore pressure generated in the cyclic tests was investigated and was found to be significantly influenced by the static shear stress. A pore pressure generation model is proposed to obtain the pore pressure characteristics of sand under various static shear stress conditions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) ...anti–vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as “RTH258” and “ESBA1008”) is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness CST, intraretinal fluid IRF, or subretinal fluid SRF) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.
Abstract
Semi-device-independent certification of an unsharp instrument has recently been demonstrated (2019
New J. Phys.
21
083034) based on the sequential sharing of quantum advantages in a ...prepare-measure communication game by assuming the system to be qubit. In this work, we provide device-independent (DI) self-testing of the unsharp instrument through the quantum violation of two Bell inequalities where the devices are uncharacterized and the dimension of the system remains unspecified. We introduce an elegant sum-of-squares approach to derive the dimension-independent optimal quantum violation of Bell inequalities which plays a crucial role. Note that the standard Bell test cannot self-test the post-measurement states and consequently cannot self-test unsharp instrument. The sequential Bell test possess the potential to self-test an unsharp instrument. We demonstrate that there exists a trade-off between the maximum sequential quantum violations of the Clauser–Horne–Shimony–Holt inequality, and they form an optimal pair that enables the DI self-testing of the entangled state, the observables, and the unsharpness parameter. Further, we extend our study to the case of elegant Bell inequality and we argue that it has two classical bounds—the local bound and the non-trivial preparation non-contextual bound, lower than the local bound. Based on the sharing of preparation contextuality by three independent sequential observers, we demonstrate the DI self-testing of two unsharpness parameters. Since an actual experimental scenario involves losses and imperfection, we demonstrate robustness of our certification to noise.
Reputation and impact in academic careers Petersen, Alexander Michael; Fortunato, Santo; Pan, Raj K. ...
Proceedings of the National Academy of Sciences - PNAS,
10/2014, Volume:
111, Issue:
43
Journal Article
Peer reviewed
Open access
Reputation is an important social construct in science, which enables informed quality assessments of both publications and careers of scientists in the absence of complete systemic information. ...However, the relation between reputation and career growth of an individual remains poorly understood, despite recent proliferation of quantitative research evaluation methods. Here, we develop an original framework for measuring how a publication’s citation rate Δ c depends on the reputation of its central author i , in addition to its net citation count c . To estimate the strength of the reputation effect, we perform a longitudinal analysis on the careers of 450 highly cited scientists, using the total citations C ᵢ of each scientist as his/her reputation measure. We find a citation crossover c ×, which distinguishes the strength of the reputation effect. For publications with c < c ×, the author’s reputation is found to dominate the annual citation rate. Hence, a new publication may gain a significant early advantage corresponding to roughly a 66% increase in the citation rate for each tenfold increase in C ᵢ. However, the reputation effect becomes negligible for highly cited publications meaning that, for c ≥ c ×, the citation rate measures scientific impact more transparently. In addition, we have developed a stochastic reputation model, which is found to reproduce numerous statistical observations for real careers, thus providing insight into the microscopic mechanisms underlying cumulative advantage in science.
Significance Over a scientist’s career, a reputation is developed, a standing within a research community, based largely upon the quantity and quality of his/her publications. Here, we develop a framework for quantifying the influence author reputation has on a publication’s future impact. We find author reputation plays a key role in driving a paper’s citation count early in its citation life cycle, before a tipping point, after which reputation has much less influence relative to the paper’s citation count. In science, perceived quality, and decisions made based on those perceptions, is increasingly linked to citation counts. Shedding light on the complex mechanisms driving these quantitative measures facilitates not only better evaluation of scientific outputs but also a more transparent evaluation of the scientists producing them.
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Smoothed particle hydrodynamics (SPH) is a Lagrangian method based on a meshless discretization of partial differential equations. In this review, we present SPH discretization of the Navier-Stokes ...and advection-diffusion-reaction equations, implementation of various boundary conditions, and time integration of the SPH equations, and we discuss applications of the SPH method for modeling pore-scale multiphase flows and reactive transport in porous and fractured media.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper presents a systematic experimental investigation into the liquefaction behavior of saturated sand subject to cyclic loadings with various types of random time histories. The triaxial test ...results indicate that the pore pressure generation and liquefaction resistance of sand are significantly influenced by the amplitude and sequence of stress pulses in the random loadings. The energy-based method using the energy density concept was applied in liquefaction assessment, which is found to be superior to the conventional equivalent approach that involving uniform stress cycles and can better capture the effect of loading randomness on the liquefaction behavior of sand.
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Summary Background It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. ...Methods We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration—the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov , numbers NCT01345006 and NCT01344993. Findings Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study ETDRS visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28). Interpretation The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue. Funding Advanced Cell Technology.
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