Towards Generalizable Diabetic Retinopathy Grading in Unseen Domains

Diabetic Retinopathy (DR) is a common complication of diabetes and a leading cause of blindness worldwide. Early and accurate grading of its severity is crucial for disease management. Although deep learning has shown great potential for automated DR grading, its real-world deployment is still challenging due to distribution shifts among source and target domains, known as the domain generalization problem. Existing works have mainly attributed the performance degradation to limited domain shifts caused by simple visual discrepancies, which cannot handle complex real-world scenarios. Instead, we present preliminary evidence suggesting the existence of three-fold generalization issues: visual and degradation style shifts, diagnostic pattern diversity, and data imbalance. To tackle these issues, we propose a novel unified framework named Generalizable Diabetic Retinopathy Grading Network (GDRNet). GDRNet consists of three vital components: fundus visual-artifact augmentation (FundusAug), dynamic hybrid-supervised loss (DahLoss), and domain-class-aware re-balancing (DCR). FundusAug generates realistic augmented images via visual transformation and image degradation, while DahLoss jointly leverages pixel-level consistency and image-level semantics to capture the diverse diagnostic patterns and build generalizable feature representations. Moreover, DCR mitigates the data imbalance from a domain-class view and avoids undesired over-emphasis on rare domain-class pairs. Finally, we design a publicly available benchmark for fair evaluations. Extensive comparison experiments against advanced methods and exhaustive ablation studies demonstrate the effectiveness and generalization ability of GDRNet.Comment: Earyly Accepted by MICCAI 2023, the 26th International Conference on Medical Image Computing and Computer Assisted Interventio

Heuristic Learning for Co-Design Scheme of Optimal Sequential Attack

This paper considers a novel co-design problem of the optimal \textit{sequential} attack, whose attack strategy changes with the time series, and in which the \textit{sequential} attack selection strategy and \textit{sequential} attack signal are simultaneously designed. Different from the existing attack design works that separately focus on attack subsets or attack signals, the joint design of the attack strategy poses a huge challenge due to the deep coupling relation between the \textit{sequential} attack selection strategy and \textit{sequential} attack signal. In this manuscript, we decompose the sequential co-design problem into two equivalent sub-problems. Specifically, we first derive an analytical closed-form expression between the optimal attack signal and the sequential attack selection strategy. Furthermore, we prove the finite-time inverse convergence of the critical parameters in the injected optimal attack signal by discrete-time Lyapunov analysis, which enables the efficient off-line design of the attack signal and saves computing resources. Finally, we exploit its relationship to design a heuristic two-stage learning-based joint attack algorithm (HTL-JA), which can accelerate realization of the attack target compared to the one-stage proximal-policy-optimization-based (PPO) algorithm. Extensive simulations are conducted to show the effectiveness of the injected optimal sequential attack

PAPER-64 Constraints On Reionization II: The Temperature Of The z=8.4 Intergalactic Medium

We present constraints on both the kinetic temperature of the intergalactic medium (IGM) at z=8.4, and on models for heating the IGM at high-redshift with X-ray emission from the first collapsed objects. These constraints are derived using a semi-analytic method to explore the new measurements of the 21 cm power spectrum from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER), which were presented in a companion paper, Ali et al. (2015). Twenty-one cm power spectra with amplitudes of hundreds of mK^2 can be generically produced if the kinetic temperature of the IGM is significantly below the temperature of the Cosmic Microwave Background (CMB); as such, the new results from PAPER place lower limits on the IGM temperature at z=8.4. Allowing for the unknown ionization state of the IGM, our measurements find the IGM temperature to be above ~5 K for neutral fractions between 10% and 85%, above ~7 K for neutral fractions between 15% and 80%, or above ~10 K for neutral fractions between 30% and 70%. We also calculate the heating of the IGM that would be provided by the observed high redshift galaxy population, and find that for most models, these galaxies are sufficient to bring the IGM temperature above our lower limits. However, there are significant ranges of parameter space that could produce a signal ruled out by the PAPER measurements; models with a steep drop-off in the star formation rate density at high redshifts or with relatively low values for the X-ray to star formation rate efficiency of high redshift galaxies are generally disfavored. The PAPER measurements are consistent with (but do not constrain) a hydrogen spin temperature above the CMB temperature, a situation which we find to be generally predicted if galaxies fainter than the current detection limits of optical/NIR surveys are included in calculations of X-ray heating.Comment: companion paper to Ali et al. (2015), ApJ 809, 61; matches version accepted to ApJ; 11 pages, 7 figure

The Hydrogen Epoch of Reionization Array Dish I: Beam Pattern Measurements and Science Implications

The Hydrogen Epoch of Reionization Array (HERA) is a radio interferometer aiming to detect the power spectrum of 21 cm fluctuations from neutral hydrogen from the Epoch of Reionization (EOR). Drawing on lessons from the Murchison Widefield Array (MWA) and the Precision Array for Probing the Epoch of Reionization (PAPER), HERA is a hexagonal array of large (14 m diameter) dishes with suspended dipole feeds. Not only does the dish determine overall sensitivity, it affects the observed frequency structure of foregrounds in the interferometer. This is the first of a series of four papers characterizing the frequency and angular response of the dish with simulations and measurements. We focus in this paper on the angular response (i.e., power pattern), which sets the relative weighting between sky regions of high and low delay, and thus, apparent source frequency structure. We measure the angular response at 137 MHz using the ORBCOMM beam mapping system of Neben et al. We measure a collecting area of 93 m^2 in the optimal dish/feed configuration, implying HERA-320 should detect the EOR power spectrum at z~9 with a signal-to-noise ratio of 12.7 using a foreground avoidance approach with a single season of observations, and 74.3 using a foreground subtraction approach. Lastly we study the impact of these beam measurements on the distribution of foregrounds in Fourier space.Comment: 13 pages, 9 figures. Replaced to match accepted ApJ versio

Hydrogen Epoch of Reionization Array (HERA)

The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to measure 21 cm emission from the primordial intergalactic medium (IGM) throughout cosmic reionization ($z=6-12$), and to explore earlier epochs of our Cosmic Dawn ($z\sim30$). During these epochs, early stars and black holes heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is designed to characterize the evolution of the 21 cm power spectrum to constrain the timing and morphology of reionization, the properties of the first galaxies, the evolution of large-scale structure, and the early sources of heating. The full HERA instrument will be a 350-element interferometer in South Africa consisting of 14-m parabolic dishes observing from 50 to 250 MHz. Currently, 19 dishes have been deployed on site and the next 18 are under construction. HERA has been designated as an SKA Precursor instrument. In this paper, we summarize HERA's scientific context and provide forecasts for its key science results. After reviewing the current state of the art in foreground mitigation, we use the delay-spectrum technique to motivate high-level performance requirements for the HERA instrument. Next, we present the HERA instrument design, along with the subsystem specifications that ensure that HERA meets its performance requirements. Finally, we summarize the schedule and status of the project. We conclude by suggesting that, given the realities of foreground contamination, current-generation 21 cm instruments are approaching their sensitivity limits. HERA is designed to bring both the sensitivity and the precision to deliver its primary science on the basis of proven foreground filtering techniques, while developing new subtraction techniques to unlock new capabilities. The result will be a major step toward realizing the widely recognized scientific potential of 21 cm cosmology.Comment: 26 pages, 24 figures, 2 table

PAPER-64 CONSTRAINTS ON REIONIZATION: THE 21 cm POWER SPECTRUM AT z = 8.4

In this paper, we report new limits on 21 cm emission from cosmic reionization based on a 135 day observing campaign with a 64-element deployment of the Donald C. Backer Precision Array for Probing the Epoch of Reionization in South Africa. This work extends the work presented in Parsons et al. with more collecting area, a longer observing period, improved redundancy-based calibration, improved fringe-rate filtering, and updated power-spectral analysis using optimal quadratic estimators. The result is a new 2σ upper limit on Δ[superscript 2](k) of (22.4 mK)[superscript 2] in the range 0.15 < k < 0.5h Mpc[superscript -1] at z = 8.4. This represents a three-fold improvement over the previous best upper limit. As we discuss in more depth in a forthcoming paper, this upper limit supports and extends previous evidence against extremely cold reionization scenarios. We conclude with a discussion of implications for future 21 cm reionization experiments, including the newly funded Hydrogen Epoch of Reionization Array

Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations.Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized.Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h−1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL.Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia