Reply

We would like to thank Drs. Debnath and Rathi for their interest in our recent article. In our study, we used data from a multicenter multiethnic cohort to identify predictors of virologic response (VR), hepatitis B surface antigen (HBsAg) loss, and alanine aminotransferase flares after nucleo(s)tide analogue withdrawal. As also highlighted by Drs Debnath and Rathi, lower levels of hepatitis B core antigen (HBcrAg) and HBsAg were associated with favorable off-treatment outcomes (ie, higher rates of VR and HBsAg loss, and lower rates of alanine aminotransferase flares). Although the observed associations were robust in subgroup analysis, it should be appreciated that neither HBcrAg nor HBsAg levels were a perfect predictor of off-treatment outcomes; patients with low viral antigen levels had higher chances favorable outcomes, but only a limited subset of patients complied with these criteria. [...

Model Predictive Control for Signal Temporal Logic Specification

We present a mathematical programming-based method for model predictive control of cyber-physical systems subject to signal temporal logic (STL) specifications. We describe the use of STL to specify a wide range of properties of these systems, including safety, response and bounded liveness. For synthesis, we encode STL specifications as mixed integer-linear constraints on the system variables in the optimization problem at each step of a receding horizon control framework. We prove correctness of our algorithms, and present experimental results for controller synthesis for building energy and climate control

Model predictive control approach to online computation of demand-side flexibility of commercial buildings HVAC systems for Supply Following

Abstract — Commercial buildings have inherent flexibility in how their HVAC systems consume electricity. We investigate how to take advantage of this flexibility. We first propose a means to define and quantify the flexibility of a commercial building. We then propose a contractual framework that could be used by the building operator and the utility to declare flexibility on the one side and reward structure on the other side. We then design a control mechanism for the building to decide its flexibility for the next contractual period to maximize the reward, given the contractual framework. Finally, we perform at-scale experiments to demonstrate the feasibility of the proposed algorithm. I

Reactive synthesis from signal temporal logic specifications

We present a counterexample-guided inductive synthesis approach to controller synthesis for cyber-physical systems subject to signal temporal logic (STL) specifications, operating in potentially adversarial nondeterministic environments. We encode STL specifications as mixed integer-linear constraints on the variables of a discrete-time model of the system and environment dynamics, and solve a series of optimization problems to yield a satisfying control sequence. We demonstrate how the scheme can be used in a receding horizon fashion to fulfill properties over unbounded horizons, and present experimental results for reactive controller synthesis for case studies in building climate control and autonomous driving

Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-neegative chronic hepatitis B:A multicentre cohort study

Background &amp; Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA &gt;2,000 IU/ml + alanine aminotransferase &gt;2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (&lt;20,000 IU/ml) in 150 (20%) and high (&gt;20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels &lt;20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels &gt;20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p &lt;0.001). In multivariable analysis, pretreatment HBV DNA levels &lt;20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p &lt;0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p &lt;0.001). Conclusions: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. Impact and Implications: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring.</p