Multicore-Aware Reuse Distance Analysis

This paper presents and validates methods to extend reuse distance analysis of application locality characteristics to shared-memory multicore platforms by accounting for invalidation-based cache-coherence and inter-core cache sharing. Existing reuse distance analysis methods track the number of distinct addresses referenced between reuses of the same address by a given thread, but do not model the effects of data references by other threads. This paper shows several methods to keep reuse stacks consistent so that they account for invalidations and cache sharing, either as references arise in a simulated execution or at synchronization points. These methods are evaluated against a Simics-based coherent cache simulator running several OpenMP and transaction-based benchmarks. The results show that adding multicore-awareness substantially improves the ability of reuse distance analysis to model cache behavior, reducing the error in miss ratio prediction (relative to cache simulation for a specific cache size) by an average of 69% for per-core caches and an average of 84% for shared caches

Evaluation of Effectiveness of Wavelet Based Denoising Schemes Using ANN and SVM for Bearing Condition Classification

The wavelet based denoising has proven its ability to denoise the bearing vibration signals by improving the signal-to-noise ratio (SNR) and reducing the root-mean-square error (RMSE). In this paper seven wavelet based denoising schemes have been evaluated based on the performance of the Artificial Neural Network (ANN) and the Support Vector Machine (SVM), for the bearing condition classification. The work consists of two parts, the first part in which a synthetic signal simulating the defective bearing vibration signal with Gaussian noise was subjected to these denoising schemes. The best scheme based on the SNR and the RMSE was identified. In the second part, the vibration signals collected from a customized Rolling Element Bearing (REB) test rig for four bearing conditions were subjected to these denoising schemes. Several time and frequency domain features were extracted from the denoised signals, out of which a few sensitive features were selected using the Fisher’s Criterion (FC). Extracted features were used to train and test the ANN and the SVM. The best denoising scheme identified, based on the classification performances of the ANN and the SVM, was found to be the same as the one obtained using the synthetic signal

Source of Previous Treatment for Re-Treatment TB Cases Registered under the National TB Control Programme, India, 2010

BACKGROUND: In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome. OBJECTIVES: To assess the source of previous treatment for re-treatment TB patients registered under India's Revised National TB control Programme (RNTCP). METHODOLOGY: A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought. RESULTS: Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 'relapse' cases, 105 'failure' cases, 437 'treatment after default (TAD)' cases and 575 're-treatment others' cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%-49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and 'retreatment others' (59%) were likely to be treated outside the National Programme, when compared to the proportion among 'relapse' (22%) or 'failure' (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme. CONCLUSIONS: Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation

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/

Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

SETTING: Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. OBJECTIVE: This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. DESIGN: Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as 'cases' and those completing treatment as 'controls'. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. RESULTS: Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. CONCLUSIONS: Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs

Cost-Effectiveness of HIV Testing Referral Strategies among Tuberculosis Patients in India

Background: Indian guidelines recommend routine referral for HIV testing of all tuberculosis (TB) patients in the nine states with the highest HIV prevalence, and selective referral for testing elsewhere. We assessed the clinical impact and cost-effectiveness of alternative HIV testing referral strategies among TB patients in India. Methods and Findings: We utilized a computer model of HIV and TB disease to project outcomes for patients with active TB in India. We compared life expectancy, cost, and cost-effectiveness for three HIV testing referral strategies: 1) selective referral for HIV testing of those with increased HIV risk, 2) routine referral of patients in the nine highest HIV prevalence states with selective referral elsewhere (current standard), and 3) routine referral of all patients for HIV testing. TB-related data were from the World Health Organization. HIV prevalence among TB patients was 9.0% in the highest prevalence states, 2.9% in the other states, and 4.9% overall. The selective referral strategy, beginning from age 33.50 years, had a projected discounted life expectancy of 16.88 years and a mean lifetime HIV/TB treatment cost of US$100. The current standard increased mean life expectancy to 16.90 years with additional per-person cost of US$10; the incremental cost-effectiveness ratio was US$650/year of life saved (YLS) compared to selective referral. Routine referral of all patients for HIV testing increased life expectancy to 16.91 years, with an incremental cost-effectiveness ratio of US$730/YLS compared to the current standard. For HIV-infected patients cured of TB, receiving antiretroviral therapy increased survival from 4.71 to 13.87 years. Results were most sensitive to the HIV prevalence and the cost of second-line antiretroviral therapy. Conclusions: Referral of all patients with active TB in India for HIV testing will be both effective and cost-effective. While effective implementation of this strategy would require investment, routine, voluntary HIV testing of TB patients in India should be recommended