The exact CC-function in integrable λ\lambda-deformed theories

By employing CFT techniques, we show how to compute in the context of \lambda-deformations of current algebras and coset CFTs the exact in the deformation parameters C-function for a wide class of integrable theories that interpolate between a UV and an IR point. We explicitly consider RG flows for integrable deformations of left-right asymmetric current algebras and coset CFTs. In all cases, the derived exact C-functions obey all the properties asserted by Zamolodchikov's c-theorem in two-dimensions.Comment: v1: 1+15 pages, Latex, v2: PLB version, v3: Correcting a typo in footnote

Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing Competitive Primers.

Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to drug resistance in infectious diseases is crucial for accurate prognostics, therapeutics and disease management at point-of-care. Here, we present a novel amplification method and provide universal guidelines for the detection of SNPs at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based loop-mediated isothermal amplification (sbLAMP) primers and unmodified self-stabilizing (USS) competitive primers that robustly delay or prevent unspecific amplification. Both sets of primers are incorporated into the same reaction mixture, but always targeting different alleles; one set specific to the wild type allele and the other to the mutant allele. The mechanism of action relies on thermodynamically favored hybridization of totally complementary primers, enabling allele-specific amplification. We successfully validate our method by detecting SNPs, C580Y and Y493H, in the Plasmodium falciparum kelch 13 gene that are responsible for resistance to artemisinin-based combination therapies currently used globally in the treatment of malaria. USS-sbLAMP primers can efficiently discriminate between SNPs with high sensitivity (limit of detection of 5 × 101 copies per reaction), efficiency, specificity and rapidness (<35 min) with the capability of quantitative measurements for point-of-care diagnosis, treatment guidance, and epidemiological reporting of drug-resistance

Offline Deep Reinforcement Learning and Off-Policy Evaluation for Personalized Basal Insulin Control in Type 1 Diabetes

Recent advancements in hybrid closed-loop systems, also known as the artificial pancreas (AP), have been shown to optimize glucose control and reduce the self-management burdens for people living with type 1 diabetes (T1D). AP systems can adjust the basal infusion rates of insulin pumps, facilitated by real-time communication with continuous glucose monitoring. Empowered by deep neural networks, deep reinforcement learning (DRL) has introduced new paradigms of basal insulin control algorithms. However, all the existing DRL-based AP controllers require a large number of random online interactions between the agent and environment. While this can be validated in T1D simulators, it becomes impractical in real-world clinical settings. To this end, we propose an offline DRL framework that can develop and validate models for basal insulin control entirely offline. It comprises a DRL model based on the twin delayed deep deterministic policy gradient and behavior cloning, as well as off-policy evaluation (OPE) using fitted Q evaluation. We evaluated the proposed framework on an in silico dataset containing 10 virtual adults and 10 virtual adolescents, generated by the UVA/Padova T1D simulator, and the OhioT1DM dataset, a clinical dataset with 12 real T1D subjects. The performance on the in silico dataset shows that the offline DRL algorithm significantly increased time in range while reducing time below range and time above range for both adult and adolescent groups. The high Spearman's rank correlation coefficients between actual and estimated policy values indicate the accurate estimation made by the OPE. Then, we used the OPE to estimate model performance on the clinical dataset, where a notable increase in policy values was observed for each subject. The results demonstrate that the proposed framework is a viable and safe method for improving personalized basal insulin control in T1D

Dosimetric accuracy of a deterministic radiation transport based 192Ir brachytherapy treatment planning system: Part III. Comparison to Monte Carlo simulation in voxelized anatomical computational models

To compare TG43-based and Acuros deterministic radiation transport-based calculations of the BrachyVision treatment planning system (TPS) with corresponding Monte Carlo (MC) simulation results in heterogeneous patient geometries, in order to validate Acuros and quantify the accuracy improvement it marks relative to TG43

On the use of polymer gels for assessing the total geometrical accuracy in clinical Gamma Knife radiosurgery applications

The nearly tissue equivalent MRI properties and the unique ability of registering 3D dose distributions of polymer gels were exploited to assess the total geometrical accuracy in clinical Gamma Knife applications, taking into account the combined effect of the unit’s mechanical accuracy, dose delivery precision and the geometrical distortions inherent in MR images used for irradiation planning. Comparison between planned and experimental data suggests that the MR-related distortions due to susceptibility effects dominate the total clinical geometrical accuracy which was found within 1 mm. The dosimetric effect of the observed sub-millimetre uncertainties on single shot GK irradiation plans was assessed using the target percentage coverage criterion, and a considerable target dose underestimation was found

Basal Glucose Control in Type 1 Diabetes using Deep Reinforcement Learning: An In Silico Validation

People with Type 1 diabetes (T1D) require regular exogenous infusion of insulin to maintain their blood glucose concentration in a therapeutically adequate target range. Although the artificial pancreas and continuous glucose monitoring have been proven to be effective in achieving closed-loop control, significant challenges still remain due to the high complexity of glucose dynamics and limitations in the technology. In this work, we propose a novel deep reinforcement learning model for single-hormone (insulin) and dual-hormone (insulin and glucagon) delivery. In particular, the delivery strategies are developed by double Q-learning with dilated recurrent neural networks. For designing and testing purposes, the FDA-accepted UVA/Padova Type 1 simulator was employed. First, we performed long-term generalized training to obtain a population model. Then, this model was personalized with a small data-set of subject-specific data. In silico results show that the single and dual-hormone delivery strategies achieve good glucose control when compared to a standard basal-bolus therapy with low-glucose insulin suspension. Specifically, in the adult cohort (n=10), percentage time in target range [70, 180] mg/dL improved from 77.6% to 80.9% with single-hormone control, and to $85.6\%$ with dual-hormone control. In the adolescent cohort (n=10), percentage time in target range improved from 55.5% to 65.9% with single-hormone control, and to 78.8% with dual-hormone control. In all scenarios, a significant decrease in hypoglycemia was observed. These results show that the use of deep reinforcement learning is a viable approach for closed-loop glucose control in T1D

Personalized Blood Glucose Prediction for Type 1 Diabetes Using Evidential Deep Learning and Meta-Learning

The availability of large amounts of data from continuous glucose monitoring (CGM), together with the latest advances in deep learning techniques, have opened the door to a new paradigm of algorithm design for personalized blood glucose (BG) prediction in type 1 diabetes (T1D) with superior performance. However, there are several challenges that prevent the widespread implementation of deep learning algorithms in actual clinical settings, including unclear prediction confidence and limited training data for new T1D subjects. To this end, we propose a novel deep learning framework, Fast-adaptive and Confident Neural Network (FCNN), to meet these clinical challenges. In particular, an attention-based recurrent neural network is used to learn representations from CGM input and forward a weighted sum of hidden states to an evidential output layer, aiming to compute personalized BG predictions with theoretically supported model confidence. The model-agnostic meta-learning is employed to enable fast adaptation for a new T1D subject with limited training data. The proposed framework has been validated on three clinical datasets. In particular, for a dataset including 12 subjects with T1D, FCNN achieved a root mean square error of 18.64±2.60 mg/dL and 31.07±3.62 mg/dL for 30 and 60-minute prediction horizons, respectively, which outperformed all the considered baseline methods with significant improvements. These results indicate that FCNN is a viable and effective approach for predicting BG levels in T1D. The well-trained models can be implemented in smartphone apps to improve glycemic control by enabling proactive actions through real-time glucose alerts

GluGAN: Generating Personalized Glucose Time Series Using Generative Adversarial Networks

Time series data generated by continuous glucose monitoring sensors offer unparalleled opportunities for developing data-driven approaches, especially deep learning-based models, in diabetes management. Although these approaches have achieved state-of-the-art performance in various fields such as glucose prediction in type 1 diabetes (T1D), challenges remain in the acquisition of large-scale individual data for personalized modeling due to the elevated cost of clinical trials and data privacy regulations. In this work, we introduce GluGAN, a framework specifically designed for generating personalized glucose time series based on generative adversarial networks (GANs). Employing recurrent neural network (RNN) modules, the proposed framework uses a combination of unsupervised and supervised training to learn temporal dynamics in latent spaces. Aiming to assess the quality of synthetic data, we apply clinical metrics, distance scores, and discriminative and predictive scores computed by post-hoc RNNs in evaluation. Across three clinical datasets with 47 T1D subjects (including one publicly available and two proprietary datasets), GluGAN achieved better performance for all the considered metrics when compared with four baseline GAN models. The performance of data augmentation is evaluated by three machine learning-based glucose predictors. Using the training sets augmented by GluGAN significantly reduced the root mean square error for the predictors over 30 and 60-minute horizons. The results suggest that GluGAN is an effective method in generating high-quality synthetic glucose time series and has the potential to be used for evaluating the effectiveness of automated insulin delivery algorithms and as a digital twin to substitute for pre-clinical trials