IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. This disease, discovered in 1968, is characterized by IgA-IgG glomerular immunodeposits with a mesangial pattern. It is ...thought that these immunodeposits originate from the immune complexes formed in the circulation. It is hypothesized that the pathogenesis of IgAN is driven by aberrant glycoforms of IgA1 (galactose-deficient IgA1, Gd-IgA1). Gd-IgA1, in genetically susceptible individuals, represents the initiating factor for the formation of circulating immune complexes due to its recognition by IgG autoantibodies and the subsequent formation of pathogenic IgA1-IgG immune complexes. Complement activation through alternative and/or lectin pathways is likely playing an important role in the pathogenic properties of these complexes and may further upregulate local inflammatory responses and glomerular injury.
IgA nephropathy (IgAN) represents the leading cause of kidney failure among East Asian populations and the most frequent form of primary glomerulonephritis among Europeans. Patients with IgAN develop ...characteristic IgA1-containing immune complexes that deposit in the glomerular mesangium, producing progressive kidney injury. Recent studies define IgAN as an autoimmune trait of complex architecture with a strong genetic determination. This Review summarizes new insights into the role of the O-glycosylation pathway, anti-glycan immune response, mucosal immunity, antigen processing and presentation, and the alternative complement pathway in the pathogenesis of IgAN.
We present a robust, unbiased technique for intelligent light‐path construction in path‐tracing algorithms. Inspired by existing path‐guiding algorithms, our method learns an approximate ...representation of the scene's spatio‐directional radiance field in an unbiased and iterative manner. To that end, we propose an adaptive spatio‐directional hybrid data structure, referred to as SD‐tree, for storing and sampling incident radiance. The SD‐tree consists of an upper part—a binary tree that partitions the 3D spatial domain of the light field—and a lower part—a quadtree that partitions the 2D directional domain. We further present a principled way to automatically budget training and rendering computations to minimize the variance of the final image. Our method does not require tuning hyperparameters, although we allow limiting the memory footprint of the SD‐tree. The aforementioned properties, its ease of implementation, and its stable performance make our method compatible with production environments. We demonstrate the merits of our method on scenes with difficult visibility, detailed geometry, and complex specular‐glossy light transport, achieving better performance than previous state‐of‐the‐art algorithms.
The wide adoption of path‐tracing algorithms in high‐end realistic rendering has stimulated many diverse research initiatives. In this paper we present a coherent survey of methods that utilize Monte ...Carlo integration for estimating light transport in scenes containing participating media. Our work complements the volume‐rendering state‐of‐the‐art report by Cerezo et al. CPP*05; we review publications accumulated since its publication over a decade ago, and include earlier methods that are key for building light transport paths in a stochastic manner. We begin by describing analog and non‐analog procedures for free‐path sampling and discuss various expected‐value, collision, and track‐length estimators for computing transmittance. We then review the various rendering algorithms that employ these as building blocks for path sampling. Special attention is devoted to null‐collision methods that utilize fictitious matter to handle spatially varying densities; we import two “next‐flight” estimators originally developed in nuclear sciences. Whenever possible, we draw connections between image‐synthesis techniques and methods from particle physics and neutron transport to provide the reader with a broader context.
Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for ...intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio HR, 0.75; 95% confidence interval CI, 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
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