Ikriya: Simulating Software Quality Enhancement With Selected Replacement Policies

The quality of information systems in any organization helps to determine theefficiency of the organization. Many organizations maintain a custom software portfolio, whose quality is important to the organization. Management would like to optimize the portfolio’s quality. Decisions about software replacement or enhancement are made based on organizational needs and priorities. The development resources allocated help in determining the quality of new software, and should be put to optimal use. Enhancing existing software might sound cheap and easy but it is not always efficient. This thesis proposes a simulation model - iKriya - for this problem. It explores the consequences of various development and maintenance policies which might be applied.These depend on the state of existing software portfolio, the queue and properties of proposed projects, and the resources available. Optimal decisions are made by the simulator by taking the above mentioned factors into consideration

Cohort profile: maternal antecedents of adiposity and studying the transgenerational role of hyperglycaemia and insulin (MAASTHI).

PURPOSE: The Maternal Antecedents of Adiposity and Studying the transgenerational role of Hyperglycaemia and Insulin cohort in Bengaluru, South India, aims to understand the transgenerational role of increased circulating glucose levels or hyperglycaemia and other nutrients and psychosocial environment, on the risk of childhood obesity, as an early marker of chronic diseases. PARTICIPANTS: Through this paper, we describe the baseline characteristics of the cohort participants and their children, along with plans and challenges. A total of 5694 pregnant women were screened, with 4862 (85.4%) eligible pregnant women recruited at baseline. We assessed anthropometry, Haemoglobin status, Oral Glucose Tolerance Test (OGTT), dietary practices, depressive symptoms using the Edinburgh Postnatal Depression Scale and social support in all women. Follow-up visits involved assessing anthropometry and the health profile of mothers and children. FINDINGS TO DATE: Among 4862 eligible participants recruited, 3260 (67%) underwent OGTT, while 2962 participants completed OGTT (90.9%). During the pregnancy, 9.7% of women were obese (>90th percentile of skinfold thickness), and 14.3% had gestational diabetesmellitus. Moreover, 6.2% and 16.8% of women had symptoms suggestive of depression during pregnancy and the immediate postnatal period, respectively. We found that 3.3% of children were small for gestational age, 10.8% were large for gestational age and 9.7% of children were obese at birth. FUTURE PLANS: We have completed recruitment and baseline data collection in 2019, and are conducting annual follow-ups until age 4 of the participant's children. For delineating causal pathways of childhood obesity, blood aliquots are stored in the biorepository. The study will inform policy formulation and community awareness in the prevention and control of non-communicable diseases and health promotion

Development of an In Vivo RNAi Protocol to Investigate Gene Function in the Filarial Nematode, Brugia malayi

Our ability to control diseases caused by parasitic nematodes is constrained by a limited portfolio of effective drugs and a paucity of robust tools to investigate parasitic nematode biology. RNA interference (RNAi) is a reverse-genetics tool with great potential to identify novel drug targets and interrogate parasite gene function, but present RNAi protocols for parasitic nematodes, which remove the parasite from the host and execute RNAi in vitro, are unreliable and inconsistent. We have established an alternative in vivo RNAi protocol targeting the filarial nematode Brugia malayi as it develops in an intermediate host, the mosquito Aedes aegypti. Injection of worm-derived short interfering RNA (siRNA) and double stranded RNA (dsRNA) into parasitized mosquitoes elicits suppression of B. malayi target gene transcript abundance in a concentration-dependent fashion. The suppression of this gene, a cathepsin L-like cysteine protease (Bm-cpl-1) is specific and profound, both injection of siRNA and dsRNA reduce transcript abundance by 83%. In vivo Bm-cpl-1 suppression results in multiple aberrant phenotypes; worm motility is inhibited by up to 69% and parasites exhibit slow-moving, kinked and partial-paralysis postures. Bm-cpl-1 suppression also retards worm growth by 48%. Bm-cpl-1 suppression ultimately prevents parasite development within the mosquito and effectively abolishes transmission potential because parasites do not migrate to the head and proboscis. Finally, Bm-cpl-1 suppression decreases parasite burden and increases mosquito survival. This is the first demonstration of in vivo RNAi in animal parasitic nematodes and results indicate this protocol is more effective than existing in vitro RNAi methods. The potential of this new protocol to investigate parasitic nematode biology and to identify and validate novel anthelmintic drug targets is discussed

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effective reduction of NOx emissions from diesel engine using split injections

Good fuel economy and high thermal efficiency of direct injection diesel engines are certainly welcome characteristics from the viewpoints of preserving energy sources and suppressing global warming. Despite the attractive fuel economy, high emissions of oxides of nitrogen (NOx) and particulate matter (PM) with their unresolved trade-off are a major challenge to be addressed by researchers. Downsizing of the engine, dilution using exhaust gases, retardation of injection timing, etc. are widely adopted techniques to lower NOx emissions. Of late, multiple/split injection strategy is garnering much attention from the researchers for its potential to effectively address NOx, soot and piston work trade-offs. The effects of variation of fuel injection timing, dilution using EGR are investigated and compared against the proposed technique of split injections (25/75 and 75/25) on a single cylinder diesel engine using numerical experiments in the present work. For this purpose, a quasi-dimensional model has been developed primarily using the derivations of first law of thermodynamics and ideal gas equation. Models predicting heat release rates, heat transfer losses, ignition delay, chemistry of combustion, NOx and soot formations are coupled to the model using phenomenological considerations. Split injection with a smaller quantity of fuel injected in the first pulse is observed to significantly lower NOx emissions due to the restrain in premixed phase of combustion of second pulse. Split injections are observed to effectively address NO-piston work trade-off compared to increasing dilution rates using EGR and retarding injection timing towards TDC. Keywords: Diesel engine, Emissions, EGR, Injection timings, NOx-piston work trade-off, Split injection

A scalable, self-sustaining model for screening and treatment of diabetic retinopathy in rural Karnataka.

The Indian health infrastructure is struggling to handle the burgeoning number of people with diabetes. Managing the complications of diabetes in an organized manner through the government health programs is still a distant reality. Here, we describe a program aimed at addressing the problem of diabetic retinopathy in rural areas of Tumkur district in Karnataka. By amalgamating telescreening and our own novel distributive care model, we were able to screen 85% of the registered diabetics in the Government noncommunicable disease clinics and treat 95% of those needing laser therapy. We also describe the importance of using electronic medical records in public health programs which not only increase the efficiency in screening for disease but help in increasing uptake of treatment by tracking defaulters