The Ci3+3 Design for Dual-Agent Combination Dose-Finding Clinical Trials

We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals that define the maximum tolerated dose combination. Ci3+3 consists of two stages to allow fast and efficient exploration of the dose-combination space. Statistical inference is restricted to a beta-binomial model for dose evaluation, and the entire design is built upon a set of fixed rules. We show via simulation studies that the Ci3+3 design exhibits similar and comparable operating characteristics to more complex designs utilizing model-based inferences. We believe that the Ci3+3 design may provide an alternative choice to help simplify the design and conduct of combination dose-finding trials in practice

Diodicity mechanism Tesla-type microvalves: a CFD study

Microvalve is one of the most important components in microfluidic systems and micropumps. In this paper, three-dimensional incompressible flow through a Tesla-type microvalve is simulated using FLUENT computational fluid dynamic package. The flow is laminar and SIMPLE algorithm is used. The second-order upwind method is implemented for discretizing convective terms. The diodicity mechanism is investigated in detail for three different microvalves. Effect of several series Tesla-type microvalves on diodicity is also studied. The numerical analyses reveal that the mechanism of diodicity occurs at the T-junction and side channel. If inlet and outlet channels are eliminated, diodicity can be increased by 2. Pressure field analysis shows that the pressure drop is much severe at the junction of the reverse flow compared to the forward flow. The obtained numerical results are compared with those of experimental and a good agreement between them is noticed

Diodicity mechanism Tesla-type microvalves: a CFD study

Microvalve is one of the most important components in microfluidic systems and micropumps. In this paper, three-dimensional incompressible flow through a Tesla-type microvalve is simulated using FLUENT computational fluid dynamic package. The flow is laminar and SIMPLE algorithm is used. The second-order upwind method is implemented for discretizing convective terms. The diodicity mechanism is investigated in detail for three different microvalves. Effect of several series Tesla-type microvalves on diodicity is also studied. The numerical analyses reveal that the mechanism of diodicity occurs at the T-junction and side channel. If inlet and outlet channels are eliminated, diodicity can be increased by 2. Pressure field analysis shows that the pressure drop is much severe at the junction of the reverse flow compared to the forward flow. The obtained numerical results are compared with those of experimental and a good agreement between them is noticed

OmniCity: Omnipotent City Understanding with Multi-level and Multi-view Images

This paper presents OmniCity, a new dataset for omnipotent city understanding from multi-level and multi-view images. More precisely, the OmniCity contains multi-view satellite images as well as street-level panorama and mono-view images, constituting over 100K pixel-wise annotated images that are well-aligned and collected from 25K geo-locations in New York City. To alleviate the substantial pixel-wise annotation efforts, we propose an efficient street-view image annotation pipeline that leverages the existing label maps of satellite view and the transformation relations between different views (satellite, panorama, and mono-view). With the new OmniCity dataset, we provide benchmarks for a variety of tasks including building footprint extraction, height estimation, and building plane/instance/fine-grained segmentation. Compared with the existing multi-level and multi-view benchmarks, OmniCity contains a larger number of images with richer annotation types and more views, provides more benchmark results of state-of-the-art models, and introduces a novel task for fine-grained building instance segmentation on street-level panorama images. Moreover, OmniCity provides new problem settings for existing tasks, such as cross-view image matching, synthesis, segmentation, detection, etc., and facilitates the developing of new methods for large-scale city understanding, reconstruction, and simulation. The OmniCity dataset as well as the benchmarks will be available at https://city-super.github.io/omnicity

Contrasting suitability and ambition in regional carbon mitigation

Substantially enhancing carbon mitigation ambition is a crucial step towards achieving the Paris climate goal. Yet this attempt is hampered by poor knowledge on the potential cost and benefit of emission mitigation for each emitter. Here we use a global economic model to assess the mitigation costs for 27 major emitting countries and regions, and further contrast the costs against the potential benefits of mitigation valued as avoided social cost of carbon and the mitigation ambition of each region. We find a strong negative spatial correlation between cost and benefit of mitigating each ton of carbon dioxide. Meanwhile, the relative suitability of carbon mitigation, defined as the ratio of normalized benefit to normalized cost, also shows a considerable geographical mismatch with the mitigation ambition of emitters indicated in their first submitted nationally determined contributions. Our work provides important information to improve concerted climate action and formulate more efficient carbon mitigation strategies

Comparison of different predictive biomarker testing assays for PD-1/PD-L1 checkpoint inhibitors response: a systematic review and network meta-analysis

BackgroundAccurate prediction of efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors is of critical importance. To address this issue, a network meta-analysis (NMA) comparing existing common measurements for curative effect of PD-1/PD-L1 monotherapy was conducted.MethodsWe searched PubMed, Embase, the Cochrane Library database, and relevant clinical trials to find out studies published before Feb 22, 2023 that use PD-L1 immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), microsatellite instability (MSI), multiplex IHC/immunofluorescence (mIHC/IF), other immunohistochemistry and hematoxylin-eosin staining (other IHC&HE) and combined assays to determine objective response rates to anti–PD-1/PD-L1 monotherapy. Study-level data were extracted from the published studies. The primary goal of this study was to evaluate the predictive efficacy and rank these assays mainly by NMA, and the second objective was to compare them in subgroup analyses. Heterogeneity, quality assessment, and result validation were also conducted by meta-analysis.Findings144 diagnostic index tests in 49 studies covering 5322 patients were eligible for inclusion. mIHC/IF exhibited highest sensitivity (0.76, 95% CI: 0.57-0.89), the second diagnostic odds ratio (DOR) (5.09, 95% CI: 1.35-13.90), and the second superiority index (2.86). MSI had highest specificity (0.90, 95% CI: 0.85-0.94), and DOR (6.79, 95% CI: 3.48-11.91), especially in gastrointestinal tumors. Subgroup analyses by tumor types found that mIHC/IF, and other IHC&HE demonstrated high predictive efficacy for non-small cell lung cancer (NSCLC), while PD-L1 IHC and MSI were highly efficacious in predicting the effectiveness in gastrointestinal tumors. When PD-L1 IHC was combined with TMB, the sensitivity (0.89, 95% CI: 0.82-0.94) was noticeably improved revealed by meta-analysis in all studies.InterpretationConsidering statistical results of NMA and clinical applicability, mIHC/IF appeared to have superior performance in predicting response to anti PD-1/PD-L1 therapy. Combined assays could further improve the predictive efficacy. Prospective clinical trials involving a wider range of tumor types are needed to establish a definitive gold standard in future

Exploring interfacial exchange coupling and sublattice effect in heavy metal/ferrimagnetic insulator heterostructures using Hall measurements, x-ray magnetic circular dichroism, and neutron reflectometry

We use temperature-dependent Hall measurements to identify contributions of spin Hall, magnetic proximity, and sublattice effects to the anomalous Hall signal in heavy metal/ferrimagnetic insulator heterostructures with perpendicular magnetic anisotropy. This approach enables detection of both the magnetic proximity effect onset temperature and the magnetization compensation temperature and provides essential information regarding the interfacial exchange coupling. Onset of a magnetic proximity effect yields a local extremum in the temperature-dependent anomalous Hall signal, which occurs at higher temperature as magnetic insulator thickness increases. This magnetic proximity effect onset occurs at much higher temperature in Pt than W. The magnetization compensation point is identified by a sharp anomalous Hall sign change and divergent coercive field. We directly probe the magnetic proximity effect using x-ray magnetic circular dichroism and polarized neutron reflectometry, which reveal an antiferromagnetic coupling between W and the magnetic insulator. Finally, we summarize the exchange-coupling configurations and the anomalous Hall-effect sign of the magnetized heavy metal in various heavy metal/magnetic insulator heterostructures

Role of dimensional crossover on spin-orbit torque efficiency in magnetic insulator thin films

Magnetic insulators (MIs) attract tremendous interest for spintronic applications due to low Gilbert damping and absence of Ohmic loss. Magnetic order of MIs can be manipulated and even switched by spin-orbit torques (SOTs) generated through spin Hall effect and Rashba-Edelstein effect in heavy metal/MI bilayers. SOTs on MIs are more intriguing than magnetic metals since SOTs cannot be transferred to MIs through direct injection of electron spins. Understanding of SOTs on MIs remains elusive, especially how SOTs scale with the film thickness. Here, we observe the critical role of dimensionality on the SOT efficiency by systematically studying the MI layer thickness dependent SOT efficiency in tungsten/thulium iron garnet (W/TmIG) bilayers. We first show that the TmIG thin film evolves from two-dimensional to three-dimensional magnetic phase transitions as the thickness increases, due to the suppression of long-wavelength thermal fluctuation. Then, we report the significant enhancement of the measured SOT efficiency as the thickness increases. We attribute this effect to the increase of the magnetic moment density in concert with the suppression of thermal fluctuations. At last, we demonstrate the current-induced SOT switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm. The switching current density is comparable with those of heavy metal/ferromagnetic metal cases. Our findings shed light on the understanding of SOTs in MIs, which is important for the future development of ultrathin MI-based low-power spintronics