To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections ...required for treatment of diabetic macular edema (DME).
A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12.
Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001).
Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.
The reported outcomes of central retinal artery occlusion (CRAO) with or without treatment vary considerably. Although local intra-arterial fibrinolysis (LIF) using recombinant tissue plasminogen ...activator (rtPA) is a promising treatment, outcomes have not been compared in randomized trials.
Prospective randomized multicenter clinical trial (the European Assessment Group for Lysis in the Eye Study) to compare treatment outcome after conservative standard treatment (CST) and LIF for acute nonarteritic CRAO.
Between 2002 and 2007, 9 centers in Austria and Germany recruited 84 patients (40 received CST, 44 received LIF), and data for 82 patients were analyzed.
Patients (age 18-75 years) with CRAO, symptoms for 20 hours or less, and best-corrected visual acuity (BCVA) <0.5 logarithm of the minimum angle of resolution (logMAR) were randomized to the CST or LIF group.
The primary end point was BCVA after 1 month; the secondary end point was safety.
The mean interval between first symptoms and therapy was 10.99+/-5.49 hours (CST) and 12.78+/-5.77 hours (LIF). The mean BCVA (logMAR) improved significantly in both groups (CST: -0.44 standard deviation 0.55; LIF: -0.45 standard deviation 0.55; both P < 0.0001) and did not differ between groups (P=0.69). Clinically significant visual improvement (> or = 0.3 logMAR) was noted in 60.0% (CST) and 57.1% (LIF) of patients. Two patients in the CST group (4.3%) and 13 patients in the LIF group (37.1%) had adverse reactions. Because of apparently similar efficacy and the higher rate of adverse reactions in the LIF group, the study was stopped after the first interim analysis at the recommendation of the data and safety monitoring committee.
In light of these 2 therapies' similar outcomes and the higher rate of adverse reactions associated with LIF, we cannot recommend LIF for the management of acute CRAO.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
This paper investigates the prospects for the generation of interactive 3D City Models based on free geo-data available from the OpenStreetMap (OSM) project and public domain height information ...provided by the Shuttle Radar Topography Mission. In particular, the suitability and quality of the OpenStreetMap data for 3D visualizations of traffic infrastructure, buildings and points of interest (POIs) is reviewed. The diversity and quantity of the points of interest provide new opportunities and challenges in creating customized and detailed visualization of cities. Specialized web services were implemented to filter and display the data in an acceptable manner. All applied web services of the 3D spatial data infrastructure are based on standards and draft specifications of the open geospatial consortium (OGC). The service is available online at www.osm-3d.org.
Abstract
Recent developments in the methods of explainable artificial intelligence (XAI) allow researchers to explore the inner workings of deep neural networks (DNNs), revealing crucial information ...about input–output relationships and realizing how data connects with machine learning models. In this paper we explore interpretability of DNN models designed to identify jets coming from top quark decay in high energy proton–proton collisions at the Large Hadron Collider. We review a subset of existing top tagger models and explore different quantitative methods to identify which features play the most important roles in identifying the top jets. We also investigate how and why feature importance varies across different XAI metrics, how correlations among features impact their explainability, and how latent space representations encode information as well as correlate with physically meaningful quantities. Our studies uncover some major pitfalls of existing XAI methods and illustrate how they can be overcome to obtain consistent and meaningful interpretation of these models. We additionally illustrate the activity of hidden layers as neural activation pattern diagrams and demonstrate how they can be used to understand how DNNs relay information across the layers and how this understanding can help to make such models significantly simpler by allowing effective model reoptimization and hyperparameter tuning. These studies not only facilitate a methodological approach to interpreting models but also unveil new insights about what these models learn. Incorporating these observations into augmented model design, we propose the particle flow interaction network model and demonstrate how interpretability-inspired model augmentation can improve top tagging performance.
: Diabetic macular edema (DME) is a sight threatening disease and a major cause for blindness for people in working age. The pathogenesis is multifactorial and complex. The pharmacotherapy of DME ...addresses both the inhibition of vascular endothelial growth factor (VEGF) by the intravitreal injection of VEGF inhibitors and inflammatory processes by the intravitreal application of steroids. Several trials have been published reporting on the efficacy and safety of these treatments.
: This review discusses original research articles including basic science and clinical studies as well as review articles focusing on the role of inflammation and VEGF expression in DME. It discusses newly published clinical trials on intravitreal pharmacotherapy for DME. The literature was searched using Medline/PubMed and was selected given its relevance for the topic to be discussed.
: Our knowledge regarding the pathophysiology of diabetic macular edema has significantly increased. Some of these insights have been successfully transferred into current treatment strategies already including VEGF suppression or anti-inflammatory treatments using steroids. The identification of additional pathophysiological aspects and their relevance as potential treatment targets will be a future challenge in the treatment of DME. A better knowledge on the complex pathophysiology will also help to establish combination strategies.
Integrin α5β1 expression is correlated with a worse prognosis in high-grade glioma. We previously unraveled a negative crosstalk between integrin α5β1 and p53 pathway, which was proposed to be part ...of the resistance of glioblastoma to chemotherapies. The restoration of p53 tumor-suppressor function is under intensive investigations for cancer therapy. However, p53-dependent apoptosis is not always achieved by p53-reactivating compounds such as Nutlin-3a, although full transcriptional activity of p53 could be obtained. Here we investigated whether integrin α5β1 functional inhibition or repression could sensitize glioma cells to Nutlin-3a-induced p53-dependent apoptosis. We discovered that α5β1 integrin-specific blocking antibodies or small RGD-like antagonists in association with Nutlin-3a triggered a caspase (Casp) 8/Casp 3-dependent strong apoptosis in glioma cells expressing a functional p53. We deciphered the molecular mechanisms involved and we showed the crucial role of two anti-apoptotic proteins, phosphoprotein enriched in astrocytes 15 (PEA-15) and survivin in glioma cell apoptotic outcome. PEA-15 is under α5β1 integrin/AKT (protein kinase B) control and survivin is a p53-repressed target. Moreover, interconnections between integrin and p53 pathways were revealed. Indeed PEA-15 repression by specific small-interfering RNA (siRNA)-activated p53 pathway to repress survivin and conversely survivin repression by specific siRNA decreased α5β1 integrin expression. This pro-apoptotic loop could be generalized to several glioma cell lines, whatever their p53 status, inasmuch PEA-15 and survivin protein levels were decreased. Our findings identify a novel mechanism whereby inhibition of α5β1 integrin and activation of p53 modulates two anti-apoptotic proteins crucially involved in the apoptotic answer of glioma cells. Importantly, our results suggest that high-grade glioma expressing high level of α5β1 integrin may benefit from associated therapies including integrin antagonists and repressors of survivin expression.
Obesity causes diastolic dysfunction, and is one of the leading causes of heart failure with preserved ejection fraction. Myocardial relaxation is determined by both active metabolic processes such ...as impaired energetic status and steatosis, as well as intrinsic myocardial remodelling. However, the relative contribution of each to diastolic dysfunction in obesity is currently unknown.
Eighty adult subjects (48 male) with no cardiovascular risk factors across a wide range of body mass indices (18.4-53.0 kg m
) underwent magnetic resonance imaging for abdominal visceral fat, left ventricular geometry (LV mass:volume ratio) and diastolic function (peak diastolic strain rate), and magnetic resonance spectroscopy for PCr/ATP and myocardial triglyceride content.
Increasing visceral obesity was related to diastolic dysfunction (peak diastolic strain rate, r=-0.46, P=0.001). Myocardial triglyceride content (β=-0.2, P=0.008), PCr/ATP (β=-0.22, P=0.04) and LV mass:volume ratio (β=-0.61, P=0.04) all independently predicted peak diastolic strain rate (model R
0.36, P<0.001). Moderated multiple regression confirmed the full mediating roles of PCr/ATP, myocardial triglyceride content and LV mass:volume ratio in the relationship between visceral fat and peak diastolic strain rate. Of the negative effect of visceral fat on diastolic function, 40% was explained by increased myocardial triglycerides, 39% by reduced PCr/ATP and 21% by LV concentric remodelling.
Myocardial energetics and steatosis are more important in determining LV diastolic function than concentric hypertrophy, accounting for more of the negative effect of obesity on diastolic function than LV geometric remodelling. Targeting these metabolic processes is an attractive strategy to treat diastolic dysfunction in obesity.
We describe a new B-meson full reconstruction algorithm designed for the Belle experiment at the B-factory KEKB, an asymmetric e
+e
− collider that collected a data sample of 771.6×10
6
B
B
¯
pairs ...during its running time. To maximize the number of reconstructed B decay channels, it utilizes a hierarchical reconstruction procedure and probabilistic calculus instead of classical selection cuts. The multivariate analysis package NeuroBayes was used extensively to hold the balance between highest possible efficiency, robustness and acceptable consumption of CPU time.
In total, 1104 exclusive decay channels were reconstructed, employing 71 neural networks altogether. Overall, we correctly reconstruct one B
± or B
0 candidate in 0.28% or 0.18% of the
B
B
¯
events, respectively. Compared to the cut-based classical reconstruction algorithm used at the Belle experiment, this is an improvement in efficiency by roughly a factor of 2, depending on the analysis considered.
The new framework also features the ability to choose the desired purity or efficiency of the fully reconstructed sample freely. If the same purity as for the classical full reconstruction code is desired (
∼
25
%
), the efficiency is still larger by nearly a factor of 2. If, on the other hand, the efficiency is chosen at a similar level as the classical full reconstruction, the purity rises from
∼
25
%
to nearly 90%.
► A method for full reconstruction of B-mesons was built. ► A hierarchical model with multivariate techniques in each step was used. ► Instead of cuts, probabilities were calculated and feed to higher stages. ► Compared to cut-based methods we achieved a factor of 2 in efficiency.
A foundational set of findable, accessible, interoperable, and reusable (FAIR) principles were proposed in 2016 as prerequisites for proper data management and stewardship, with the goal of enabling ...the reusability of scholarly data. The principles were also meant to apply to other digital assets, at a high level, and over time, the FAIR guiding principles have been re-interpreted or extended to include the software, tools, algorithms, and workflows that produce data. FAIR principles are now being adapted in the context of AI models and datasets. Here, we present the perspectives, vision, and experiences of researchers from different countries, disciplines, and backgrounds who are leading the definition and adoption of FAIR principles in their communities of practice, and discuss outcomes that may result from pursuing and incentivizing FAIR AI research. The material for this report builds on the FAIR for AI Workshop held at Argonne National Laboratory on June 7, 2022.
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