Hardware Accelerator for HMM Based Speech Recognition using Approximate Computing Techniques

This thesis presents a hardware design for recognizing speech using phoneme-level Hidden Markov Models (HMMs) and proposes two alternative designs using approximate computing techniques for area and energy optimizations. An initial hardware design is proposed to model a speech recognition system using the log-Viterbi algorithm approach. Two more hardware designs using various approximate computing techniques and modifications to the log-Viterbi algorithm are also proposed, that are shown to consume lesser area and power. The work also presents the performance analysis in terms of recognition accuracy and hardware evaluations in terms of area, switching and leakage power and energy dissipation of all three designs. The results prove that the usage of approximate computing helps reduce area and power, with a minor compromise on accuracy. The design using approximate computing is also capable of running at a higher frequency with quicker execution time and lesser energy consumption. For applications where accuracy is vital, the thesis also proposes an adaptive system which can operate in two modes – one at a higher frequency, with slightly lesser accuracy and another at a lower frequency, with better accuracy and capable of dynamically switching from one mode to another

The barriers and enablers to education among scheduled caste and scheduled tribe adolescent girls in northern Karnataka, South India: A qualitative study

This qualitative study explored the barriers and enablers to scheduled caste/scheduled tribe (SC/ST) adolescent girls entering into, and completing secondary education in northern Karnataka, South India. In-depth interviews were conducted with 22 adolescent girls, their respective parent/guardian (n = 22) and 11 teachers, recruited purposively from 11 villages within two districts in northern Karnataka. Multiple barriers were identified to disadvantaged caste adolescent girls’ entry into and retention in education in this setting, and these operated at the individual, family, community and school levels. In addition, some enablers to education were also described. The study highlights the importance of involving multiple stakeholders to overcome the barriers to education for SC/ST girls, and of working to change beliefs and expectations around gender norms as well as improving the quality of education in this setting

Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: Patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

BACKGROUND: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). AIM: To evaluate patient-reported outcomes (PROs) in this population. METHODS: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. RESULTS: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and \u3e80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. CONCLUSION: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION: NCT02477826

Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: Patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

BACKGROUND: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). AIM: To evaluate patient-reported outcomes (PROs) in this population. METHODS: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. RESULTS: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and \u3e80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. CONCLUSION: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION: NCT02477826

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Correlates of school dropout and absenteeism among adolescent girls from marginalized community in north Karnataka, south India.

Secondary education among lower caste adolescent girls living in rural Karnataka, South India, is characterized by high rates of school drop-out and absenteeism. A cross-sectional baseline survey (N=2275) was conducted in 2014 as part of a cluster-randomized control trial among adolescent girls (13-14 year) and their families from marginalized communities in two districts of north Karnataka. Bivariate and multivariate logistic regression models were used. Overall, 8.7% girls reported secondary school dropout and 8.1% reported frequent absenteeism (past month). In adjusted analyses, economic factors (household poverty; girls' work-related migration), social norms and practices (child marriage; value of girls' education), and school-related factors (poor learning environment and bullying/harassment at school) were associated with an increased odds of school dropout and absenteeism. Interventions aiming to increase secondary school retention among marginalized girls may require a multi-level approach, with synergistic components that address social, structural and economic determinants of school absenteeism and dropout

Evaluation of Stability of Implants Placed Simultaneously with Lateral Window Sinus Augmentation using Putty Alloplastic Bone Substitute: A Prospective Interventional Study

Introduction: Lateral window sinus augmentation is done to augment the vertical sinus height for implant placement. Putty alloplasts have been used due to their longer resorption time and provide resistance to implant insertion. Although, widely used, the stability and bone loss around implants placed simultaneously following sinus augmentation with putty bone graft has not been evaluated. Aim: To evaluate the effect of putty alloplastic bone substitute on implant stability. Materials and Methods: This prospective interventional study was conducted in the Outpatient Department (OPD) of Oral and Maxillofacial surgery at SGT Dental College and Research Institute, Gurugram, Haryana, India. The duration of the study was two years and 11 months, from December 2014-November 2016. A total of 15 implants were placed simultaneously after lateral window sinus augmentation. Primary implant stability measurements were done using Resonance Frequency Analysis (RFA). Vertical Bone Height (VBH), Maximum Insertion Torque (MIT) and Crestal Bone Loss (CBL) were measured till six months of follow-up. The data was analysed using standard statistical analyses with Shapiro-Wilk-test, Wilcoxon signed-rank test and Spearman’s correlation co-efficient. Results: The mean age of the study participants was 58±3.04 years. A total of 15 implants were placed in 12 patients. Adequate primary stability was achieved with MIT >36 N/cm2 in 9/15 patients whereas, in 6/15 patients the MIT was ≤36 N/cm2 . The implants showed 100% survival rate. Postoperative bone gain obtained was in the range of 7.89 mm to 11.9 mm, with a mean of 9.92 mm. Acceptable levels of implant stability were obtained after six months. Conclusion: Within the limitations of the study, it can be concluded that, putty bone alloplast can serve as an adequate bone substitute in simultaneous implant placement after lateral window sinus augmentation and help in achieving stability

Zebrafish: A Model to Study and Understand the Diabetic Nephropathy and Other Microvascular Complications of Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a complicated metabolic illness that has had a worldwide impact and placed an unsustainable load on both developed and developing countries’ health care systems. According to the International Diabetes Federation, roughly 537 million individuals had diabetes in 2021, with type 2 diabetes mellitus accounting for the majority of cases (T2DM). T2DM is a chronic illness defined by insufficient insulin production from pancreatic islet cells. T2DM generates various micro and macrovascular problems, with diabetic nephropathy (DN) being one of the most serious microvascular consequences, and which can lead to end-stage renal disease. The zebrafish (Danio rerio) has set the way for its future as a disease model organism. As numerous essential developmental processes, such as glucose metabolism and reactive metabolite production pathways, have been identified in zebrafish that are comparable to those seen in humans, it is a good model for studying diabetes and its consequences. It also has many benefits over other vertebrate models, including the permeability of its embryos to small compounds, disease-driven therapeutic target selection, in vivo validation, and deconstruction of biological networks. The organism can also be utilized to investigate and understand the genetic abnormalities linked to the onset of diabetes problems. Zebrafish may be used to examine and visualize the growth, morphology, and function of organs under normal physiological and diabetic settings. The zebrafish has become one of the most useful models for studying DN, especially when combined with genetic alterations and/or mutant or transgenic fish lines. The significant advancements of CRISPR and next-generation sequencing technology for disease modelling in zebrafish, as well as developments in molecular and nano technologies, have advanced the understanding of the molecular mechanisms of several human diseases, including DN. In this review, we emphasize the physiological and pathological processes relating to microvascular problems in zebrafish, as well as the many experimental zebrafish models used to research DN, and the DN-related outcomes and mechanisms observed in zebrafish