EXPLORING EFFICACY OF AN ANTI-MALARIAL NANOMEDICINE IN NON-SMALL CELL LUNG CANCER TREATMENT

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes and formulation parameters so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded nanoparticles (AQ NP) were evaluated for physicochemical properties, stability profile, in-vitro aerosol deposition behavior, cytotoxic potential against NSCLC cells in-vitro and in 3D simulated tumor spheroid model while the results confirming the significance of nanoparticle encapsulation for an enhanced anti-cancer efficacy. Furthermore, targeting potential of transferrin ligand conjugated AQ-loaded nanoparticles (Tf-AMQ NPs) was investigated, also evaluated for their physicochemical properties. Tf-AMQ NP (liquid state) exhibited an aerodynamic diameter of 4.4±0.1 µm and fine particle fraction of 83.2±3.0%, indicating drug deposition in the respirable airways. Cytotoxicity studies in NSCLC cell line with overexpressed transferrin receptors revealed significant reduction in IC50 values with Tf-decorated AQ-loaded nanoparticles compared to plain drug or non-targeted NPs, along with significant apoptosis induction (caspase assay) and reduced % colony growth in A549 and H1299 cells with Tf-AMQ NP. Moreover, 3D simulated spheroid studies (~ 7-fold reduction in spheroid volume compared to AMQ NPs) revealed efficacy of conjugated nanoparticles in penetration to tumor core, and growth inhibition. AQ’s autophagy inhibition ability significantly increased with nanoparticle encapsulation and transferrin conjugation. Further, another ligand folic acid has been explored for its ability to be conjugated to nanoparticles and to enhance anti-cancer efficacy and were found to exhibit superior anti-cancer efficacy in multiple cancer types such as breast cancer and cervical cancer. To conclude, amodiaquine can be a promising candidate for repurposing to treat NSCLC while delivering inhalable transferrin conjugated nanoparticles developed using a scalable HPH process to the target site, thus reducing the dose, side effects

Perinatal outcome in pregnancies complicated with oligohydramnios at term

Background: AFI of less than or equal to five cm is considered oligohydramnios. Various approaches, such as NST, acoustic stimulation, and foetal Doppler velocimetry, are useful in assessing foetal well-being and identifying pregnancies at risk of postnatal complications. The goal of this study was to learn about the negative perinatal outcomes in pregnant women who had oligohydramnios at term and to assess the efficacy of AFI in predicting foetal distress and caesarean delivery.Methods: A retrospective and comparative study of singleton pregnancies outcomes in 60 women diagnosed with oligohydramnios by USG after 37 weeks of pregnancy, compared to 60 women who did not have oligohydramnios and were matched for other factors. Some criteria for inclusion and exclusion were utilised. The data was analysed using statistical criteria such as mean, standard deviation, and chi square test sensitivity, specificity, PPV, and NPV.Results: The occurrence of non-reactive and re-active NST patterns differed significantly between the two groups. In comparison to women with AFI >5 cm, women with AFI 5cm have a higher rate of labour induction. LBW (2.5 kg) was more common in women with oligohydramnios, and LSCS rates were higher in oligohydramnios-complicated pregnancies.Conclusions: After 37 weeks of pregnancy, an AFI of less than 5 cm is a sign of poor perinatal outcome. AFI can be used in conjunction with other foetal monitoring techniques. AFI is a useful screening test for predicting foetal distress during labour that necessitates a caesarean section

Technical Advances and Pitfalls in Head and Neck Radiotherapy

Intensity Modulated Radiotherapy (IMRT) is the standard of care in the treatment of head and neck squamous cell carcinomas (HNSCC) based on level 1 evidence. Technical advances in radiotherapy have revolutionized the treatment of HNSCC, with the most tangible gain being a reduction in long term morbidity. However, these benefits come with a serious and sobering price. Today, there is a greater chance of missing the target/tumor due to uncertainties in target volume definition by the clinician that is demanded by the highly conformal planning process involved with IMRT. Unless this is urgently addressed, our patients would be better served with the historically practiced non conformal radiotherapy, than IMRT which promises lesser morbidity. Image guided radiotherapy (IGRT) ensures the level of set up accuracy warranted to deliver a highly conformal treatment plan and should be utilized with IMRT, where feasible. Proton therapy has a theoretical physical advantage over photon therapy due to a lack of “exit dose”. However, clinical data supporting the routine use of this technology for HNSCC are currently sparse. The purpose of this article is to review the literature, discuss the salient issues and make recommendations that address the gaps in knowledge

Random sampling in Apache Hive

Data generated by humans and machines is growing at a rapid pace. Analyzing the data provides trends, patterns, and useful insights in data which helps to make important organizational decisions. Traditional database systems have been storing and analyzing large amounts of data for many decades. In traditional databases, handling and analyzing growing data needs lots of resources and time. Reading and writing large data from a single disk is significantly slow. Storing and reading from multiple disks and combining them for analyzing on a single CPU is also not reasonable for huge amounts of data. The problem of storing and analyzing large amount of data is handled by Apache Hadoop. Apache Hadoop is a collection of open source big data software’s that can efficiently handle storing large amounts of data by dividing data into small blocks and replicates the data to handle system failures. Data is analyzed based on the concept of parallel computation. Hive is a data warehousing software that works on top of Hadoop file system. It has an Hive QL interface to execute queries, and are automatically converted into map reduce or tez or spark jobs. For aggregate queries like AVG, SUM, count e.t.c., and for analyzing trends in data, sampling gives good approximation about overall data. Analyzing sample population can be achieved with limited amount of resources. There are different sampling techniques to draw sample from a population, and choice of sampling technique depends on type of analysis we perform to achieve the goal. In this thesis, we have investigated three techniques to perform random sampling on Hive: simple random sampling using sorting, Bernoulli’s sampling, and our algorithm random sampling using bucketing. Simple random sampling using sorting, and Bernoulli’s sampling goes through the whole data to perform sampling in Hive. This slows down the performance when the data is huge. To avoid whole table scan while performing simple random sampling, our algorithm uses bucketing in hive architecture to manage the data stored on Hadoop Distributed File System. Bucketing divides the whole data into specified number of small blocks. Data is divided into buckets based on a specified column in a table. Bucketing allows to select any bucket of required size without scanning the whole table. Limiting data scan and sorting fewer elements decreases the time taken to perform simple random sampling using bucketing. Our experiments shows random sampling using bucketing performs much faster than random sampling using sorting and Bernoulli sampling when the data sizes or sample sizes are large

Evaluation of Test Procedures for the Raveling Test in Cold Recycling Mix Designs

Cold In-Place Recycling (CIR) method is one of the forms of asphalt pavement recycling which is environmental friendly and cost effective. With CIR a milling machine removes the asphalt pavement to a depth of 3 to 5 inches. The reclaimed asphalt pavement (RAP) is then sized and mixed with a bituminous recycling agent. Bituminous recycling agents consist of either emulsified asphalts or foamed (expanded) asphalt. The treated RAP is then placed and compacted using conventional asphalt paving equipment. The CIR process recycles 100 percent of the RAP in place without the application of heat.Currently there are no nationally accepted mix design methods for CIR mixtures. The CIR mix design procedures adopted by most state highway agencies originated from mix design procedures developed by equipment and materials suppliers. Most agencies follow the mix design procedures developed by Wirtgen (1) for CIR with foamed asphalt. Most CIR mix designs using emulsified asphalt are based on procedures developed by Road Science and their predecessors. . As per ARRA (2), CIR mix designs with emulsified asphalt consist of evaluating the strength of the recycled mixture using Marshall stability or indirect tensile strength, retained Marshall stability or tensile strength ratio to evaluate resistance to moisture induced damage, and the Raveling test (ASTM D7196) is performed to evaluate the emulsified asphalt�s breaking and curing properties and the mixtures resistance to raveling under initial traffic. Road Science and their predecessors hold a patent on the mix design process and the use of raveling test in combination with other tests. The patents have not been uniformly enforced over the years causing uncertainty about the use of the Raveling test as a part of CIR mix designs, resulting in reluctance on the part of some agencies to use CIR with emulsified asphalts.Civil Engineerin