A Unified Framework for Consensus and Synchronization on Lie Groups admitting a Bi-Invariant Metric

For a finite number of agents evolving on a Euclidean space and linked to each other by a connected graph, the Laplacian flow that is based on the inter-agent errors, ensures consensus or synchronization for both first and second-order dynamics. When such agents evolve on a circle (the Kuramoto oscillator), the flow that depends on the sinusoid of the inter-agent error angles generalizes the same. In this work, it is shown that the Laplacian flow and the Kuramoto oscillator are special cases of a more general theory of consensus on Lie groups that admit bi-invariant metrics. Such a theory not only enables generalization of these consensus and synchronization algorithms to Lie groups but also provide insight on to the abstract group theoretic and differential geometric properties that ensures convergence in Euclidean space and the circle

BDD Minimization for Approximate Computing

We present Approximate BDD Minimization (ABM) as a problem that has application in approximate computing. Given a BDD representation of a multi-output Boolean function, ABM asks whether there exists another function that has a smaller BDD representation but meets a threshold w.r.t. an error metric. We present operators to derive approximated functions and present algorithms to exactly compute the error metrics directly on the BDD representation. An experimental evaluation demonstrates the applicability of the proposed approaches

RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer

BACKGROUND: Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors.METHODS: This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66–70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66–70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95% CI was calculated. The hazard ratio was obtained using COX regression analysis.RESULTS: We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5–42) in CRT arm versus 57.2% (95%CI 45.8–67.1) in NCRT arm (HR -0.54; 95%CI 0.36–0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8–52.6) in the CRT arm versus in 60.4% (95%CI 48.7–70.2) in the NCRT arm (HR -0.61; 95%CI 0.4–0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4–49.6) to 57.6% (95%CI 46.3–67.4) (HR-0.63, 95%CI 0.43–0.92, p = 0.018).CONCLUSIONS: The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.<br/

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer

BACKGROUND: Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors.METHODS: This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66–70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66–70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95% CI was calculated. The hazard ratio was obtained using COX regression analysis.RESULTS: We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2- year PFS was 31.5% (95%CI 21.5–42) in CRT arm versus 57.2% (95%CI 45.8–67.1) in NCRT arm (HR -0.54; 95%CI 0.36–0.79, p = 0.002). The 2-year LRC was 41.4% (95%CI 29.8–52.6) in the CRT arm versus in 60.4% (95%CI 48.7–70.2) in the NCRT arm (HR -0.61; 95%CI 0.4–0.94, p = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4–49.6) to 57.6% (95%CI 46.3–67.4) (HR-0.63, 95%CI 0.43–0.92, p = 0.018).CONCLUSIONS: The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.<br/

Approximation-aware Rewriting of AIGs for Error Tolerant Applications

Approximation circuits offer superior performance (speed and area) compared to traditional circuits at the cost of computational accuracy. The accuracy of the results in approximation circuits is evaluated based on several error metrics such as worst-case error, bit-flip error, or error-rate. Several applications have varied requirements in error metrics, i.e., all the error criteria have to be met together at a time, or in combinations. Nevertheless, all applications benefit from improved delay and area. An automated synthesis approach with formal guarantees on error metrics is very helpful in generating circuits that meet these criteria. Furthermore, each of these metrics are independent quantities (value of one metric does not correlate with the other), and automated synthesis can discover opportunities to trade off one or more of the relaxed metrics with a strict requirement on the other, resulting in better performance. In this paper, we present an automatic synthesis approach using And-Inverter Graphs (AIGs) based rewriting that not only improves the performance but also guarantees the bounds of approximation errors introduced. Our synthesis approach is evaluated on a wide range of designs and standard benchmark circuits to show the usefulness and applicability. In particular, we show that our synthesis results are even comparable with the optimization achieved with hand crafted adhoc approximation circuits such as approximation adders in a case study on image compression

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer – A retrospective pilot analysis and viewpoint

Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study