Search results for: controlled drug delivery

Authors: Tianyu Cao, KIRA (Ruizhi Zhao)

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The purpose of our research is to study the possibility of people with physical disabilities manipulating mechanical prostheses through brain-computer interface (BCI) technology. The brain-machine interface (BCI) of the neural prosthesis records signals from neurons and uses mathematical modeling to decode them, converting desired movements into body movements. In order to improve the patient's neural control, the prosthesis is given a natural feeling. It records data from sensitive areas from the body to the prosthetic limb and encodes signals in the form of electrical stimulation to the brain. In our research, the brain-computer interface (BCI) is a bridge connecting patients’ cognition and the real world, allowing information to interact with each other. The efficient work between the two is achieved through external devices. The flow of information is controlled by BCI’s ability to record neuronal signals and decode signals, which are converted into device control. In this way, we could encode information and then send it to the brain through electrical stimulation, which has significant medical application.

Keywords: biomedical engineering, brain-computer interface, prosthesis, neural control

Procedia PDF Downloads 181

Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

Procedia PDF Downloads 245

Authors: Kuo-Chun Chien, Chia-Hui Chang, Ren-Der Sun

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Legal Judgment Prediction (LJP) is a subtask for legal AI. Its main purpose is to use the facts of a case to predict the judgment result. In Taiwan's criminal procedure, when prosecutors complete the investigation of the case, they will decide whether to prosecute the suspect and which article of criminal law should be used based on the facts and evidence of the case. In this study, we collected 305,240 indictments from the public inquiry system of the procuratorate of the Ministry of Justice, which included 169 charges and 317 articles from 21 laws. We take the crime facts in the indictments as the main input to jointly learn the prediction model for law source, article, and charge simultaneously based on the pre-trained Bert model. For single article cases where the frequency of the charge and article are greater than 50, the prediction performance of law sources, articles, and charges reach 97.66, 92.22, and 60.52 macro-f1, respectively. To understand the big performance gap between articles and charges, we used a bipartite graph to visualize the relationship between the articles and charges, and found that the reason for the poor prediction performance was actually due to the wording precision. Some charges use the simplest words, while others may include the perpetrator or the result to make the charges more specific. For example, Article 284 of the Criminal Law may be indicted as “negligent injury”, "negligent death”, "business injury", "driving business injury", or "non-driving business injury". As another example, Article 10 of the Drug Hazard Control Regulations can be charged as “Drug Control Regulations” or “Drug Hazard Control Regulations”. In order to solve the above problems and more accurately predict the article and charge, we plan to include the article content or charge names in the input, and use the sentence-pair classification method for question-answer problems in the BERT model to improve the performance. We will also consider a sequence-to-sequence approach to charge prediction.

Keywords: legal judgment prediction, deep learning, natural language processing, BERT, data visualization

Procedia PDF Downloads 121

Authors: K. Srujana, Vinay U. Rao, M. Sudhakar

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Isoniazide (INH) a freely water soluble and pyrazinamide (Z) a practically water insoluble first line anti tubercular (TB) drugs were identified as candidates for optimizing the Moisture Activated Dry Granulation (MADG) process. The work focuses on identifying the effect of binder type and concentration as well as the effect of magnesium stearate level on critical quality attributes of Disintegration time (DT) and in vitro dissolution test when the tablets are processed by the MADG process. Also, the level of the drug concentration, binder concentration and fluid addition during the agglomeration stage of the MADG process was evaluated and optimized. For INH, it was identified that for tablets with HPMC as binder at both 2% w/w and 5% w/w level and Magnesium stearate upto 1%w/w as lubrication the DT is within 1 minute and the dissolution rate is the fastest (> 80% in 15 minutes) as compared to when PVP or pregelatinized starch is used as binder. Regarding the process, fast disintegrating and rapidly dissolving tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 25% w/w 0% w/w binder and 0.033%. w/w. At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is also slower. For pyrazinamide,it was identified that for the tablets with 2% w/w level of each of PVP as binder and Cross Caramellose Sodium disintegrant the DT is within 2 minutes and the dissolution rate is the fastest(>80 in 15 minutes)as compared to when HPMC or pregelatinized starch is used as binder. This may be attributed to the fact that PVP may be acting as a solubilizer for the practically insoluble Pyrazinamide. Regarding the process,fast dispersing and rapidly disintegrating tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 10% w/w,25% w/w binder and 1% w/w.At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is comparatively slower and less complete.

Keywords: agglomeration stage, isoniazide, MADG, moisture distribution stage, pyrazinamide

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Authors: Alaaeddeen M. Seufi

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Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.

Keywords: AMPs, insect, innate immunitty, therappeutics

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Authors: Shuen-Tai Wang, Ying-Chuan Chen, Hsi-Ya Chang

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Cloud computing is a paradigm of computing that shifts the way computing has been done in the past. The users can use cloud resources such as application software or storage space from the cloud without needing to own them. This paper is focused on solutions that are anticipated to introduce IaaS idea to build cloud base services and enable the individual remote user's applications in cloud environments, which appear as if they are running on the end user's local computer. The available features of application delivery solution have been developed based on our previous research on the virtualization technology to offer applications independent of location so that the users can work online, offline, anywhere, with appropriate device and at any time. This proposed effort has the potential to positively provide an efficient, resilience and elastic environment for cloud service. Users no longer need to burden the system managers and drastically reduces the overall cost of hardware and software licenses. Moreover, this flexible remote application virtualization service represents the next significant step to the mobile workplace, and it lets users access their applications remotely through cloud services anywhere. This is also made possible by the low administrative costs as well as relatively inexpensive end-user terminals and reduced energy expenses.

Keywords: cloud computing, IaaS, virtualization, application delivery

Procedia PDF Downloads 281

Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Qian Zhang, Dongkai Shen, Yan Shi

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A new mechanical ventilator with automatic secretion clearance function can improve the secretion clearance safely and efficiently. However, in recent modeling studies on various mechanical ventilators, it was considered that human had one lung, and the coupling effect of double lungs was never illustrated. In this paper, to expound the coupling effect of double lungs, a mathematical model of a ventilation system of a bi-level positive airway pressure (BiPAP) controlled ventilator with secretion clearance was set up. Moreover, an experimental study about the mechanical ventilation system of double lungs on BiPAP ventilator was conducted to verify the mathematical model. Finally, the coupling effect of double lungs of the mathematical ventilation was studied by simulation and orthogonal experimental design. This paper adds to previous studies and can be referred to optimization methods in medical researches.

Keywords: double lungs, coupling effect, secretion clearance, orthogonal experimental design

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Authors: Farouk Shehu Abdulwahab

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The concept of farmer-farmer knowledge sharing was introduced to bridge the extension worker-farmer ratio gap in developing countries. However, the idea was poorly accepted, especially in typical agrarian communities. Therefore, the study explores the concept of a farmer-to-farmer knowledge-sharing network to enhance extension service delivery. The study collected data from 80 farmers randomly selected through a series of multiple stages. The Data was analysed using a 5-point Likert scale and descriptive statistics. The Likert scale results revealed that 62.5% of the farmers are satisfied with farmer-to-farmer knowledge-sharing networks. Moreover, descriptive statistics show that lack of capacity building and low level of education are the most significant problems affecting farmer-farmer sharing networks. The major implication of these findings is that the concept of farmer-farmer knowledge-sharing networks can work better for farmers in developing countries as it was perceived by them as a reliable alternative for information sharing. Therefore, the study recommends introducing incentives into the concept of farmer-farmer knowledge-sharing networks and enhancing the capabilities of farmers who are opinion leaders in the farmer-farmer concept of knowledge-sharing to make it more sustainable.

Keywords: agricultural productivity, extension, farmer-to-farmer, livelihood, technology transfer

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Authors: Irene Alevizos, Jessica Lewis, Marina Harper, John Boyce

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Acinetobacter baumannii causes a range of severe nosocomial-acquired infections, and many strains are multi-drug resistant. A. baumannii possesses survival mechanisms allowing it to thrive in competitive polymicrobial environments, including a Type VI Secretion System (T6SS) that injects effector proteins into other bacteria to give a competitive advantage. The effects of T6SS firing are broad and depend entirely on the effector that is delivered. Effects can include toxicity against prokaryotic or eukaryotic cells and the acquisition of essential nutrients. The T6SS of some species can deliver ‘specialised effectors’ that are fused directly to T6SS components, such as PAAR proteins. PAAR proteins are predicted to form the piercing tip of the T6SS and are essential for T6SS function. Although no specialised effectors have been identified in A. baumannii, many strains encode multiple PAAR proteins. Analysis of PAAR proteins across the species identified 12 families of PAAR proteins with distinct C-terminal extensions. A. baumannii AB307-0294 encodes two PAAR proteins, one of which has a C-terminal extension. Mutation of one or both of the PAAR-encoding genes in this strain showed that expression of either PAAR protein was sufficient for T6SS function. We employed a heterologous expression approach and determined that PAAR proteins from different A. baumannii strains, as well as the closely related A. baylyi species, could complement the A. baumannii ∆paar mutant and restore T6SS function. Furthermore, we showed that PAAR fusions could be used to deliver artificially cloned protein fragments by generating Histidine- and Streptavidin- tagged PAAR specialised effectors, which restored T6SS activity. This provides evidence that the fusion of protein fragments onto PAAR proteins in A. baumannii is compatible with a functional T6SS. Successful delivery by this mechanism extends the scope of what the T6SS can deliver, including user designed proteins.

Keywords: A. baumannii, effectors, PAAR, T6SS

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Authors: Abdel-Aziz M. Mohamed, Nermeen Coutry

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Lead time is an important measure of supply chain performance. It impacts both customer satisfactions as well as the total cost of inventory. This paper presents the result of a study on the analysis of the customer order lead-time for a multinational company. In the study, the lead time was divided into three stages: order entry, order fulfillment, and order delivery. A sample of size 2,425 order lines from the company records were considered for this study. The sample data includes information regarding customer orders from the time of order entry until order delivery. Data regarding the lead time of each sage for different orders were also provided. Summary statistics on lead time data reveals that about 30% of the orders were delivered after the scheduled due date. The result of the multiple linear regression analysis technique revealed that component type, logistics parameter, order size and the customer type have significant impact on lead time. Data analysis on the stages of lead time indicates that stage 2 consumes over 50% of the lead time. Pareto analysis was made to study the reasons for the customer order delay in each of the 3 stages. Recommendation was given to resolve the problem.

Keywords: lead time reduction, customer satisfaction, service quality, statistical analysis

Procedia PDF Downloads 729

Authors: Sanjay Singh, Swati Jaiswal, Prashant Mishra

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Nanoparticle based formulations of drug delivery systems have shown their potential in improving the performance of existing drugs and have opened avenues for new therapies. Calendula extract is a low cost, wide spectrum bioactive material that has been used for a long term therapy of various infections. Aim: The aim of this study was to develop Calendula officinalis extract based nanoformulations and to study the antibacterial activity of either Calendula extract loaded chitosan nanoparticles or Calendula extract coated silver nanoparticles for increased bioavailability and their long term effect. Methods: Chitosan nanoparticles were prepared by the process of ionotropic gelation, based on interaction between the negative groups of tri polyphosphate (TPP) and positively charged amino groups of chitosan. The size of the Calendula extract-loaded chitosan particles was determined using dynamic light scattering and scanning electron microscopy. Antibacterial activities of these formulations were determined based on minimum inhibitory concentration and time kill studies. In addition, silver nanoparticles were also synthesized in the presence of Calendula extract and characterized by UV visible spectrum, DLS and XRD. Experiments were conducted on 96-plates against two Gram-positive bacteria; Staphylococcus aureus and Bacillus subtilis two Gram-negative bacteria; Escherichia coli and Pseudomonas aeruginosa. Results: Results demonstrated time dependent antibacterial activity against different microbes studied. Both Calendula extract and Calendula extract loaded chitosan nanoparticles have shown good antimicrobial activity against both Gram positive and Gram negative bacteria. Conclusion: Calendula extract loaded chitosan nanoparticles and calendula extract coated silver nanoparticles are potential antibacterial for their long term antibacterial effects.

Keywords: antibacterial, Calendula extract, chitosan nanoparticles, silver nanoparticles

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Authors: Mensah-Akoto Julius, Kenichi Matsui

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This paper examines the impact of COVID-19 on waste management workers in Ghana. A questionnaire survey was conducted among 60 waste management workers in Accra metropolis, the capital region of Ghana, to understand the impact of the COVID-19 pandemic on waste generation, workers’ safety in collecting solid waste, and service delivery. To find out correlations between the pandemic and safety of waste management workers, a regression analysis was used. Regarding waste generation, the results show the pandemic led to the highest annual per capita solid waste generation, or 3,390 tons, in 2020. Regarding the safety of workers, the regression analysis shows a significant and inverse association between COVID-19 and waste management services. This means that contaminated wastes may infect field workers with COVID-19 due to their direct exposure. A rise in new infection cases would have a negative impact on the safety and service delivery of the workers. The result also shows that an increase in economic activities negatively impacts waste management workers. The analysis, however, finds no statistical relationship between workers’ service deliveries and employees’ salaries. The study then discusses how municipal waste management authorities can ensure safe and effective waste collection during the pandemic.

Keywords: Covid-19, waste management worker, waste collection, Ghana

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Authors: Titus A. Beu

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Many modern gene-delivery protocols rely on condensed complexes of DNA with polycations to introduce the genetic payload into cells by endocytosis. In particular, polyethyleneimine (PEI) stands out by a high buffering capacity (enabling the efficient condensation of DNA) and relatively simple fabrication. Realistic computational studies can offer essential insights into the formation process of DNA-PEI polyplexes, providing hints on efficient designs and engineering routes. We present comprehensive computational investigations of solvated PEI and DNA-PEI polyplexes involving calculations at three levels: ab initio, all-atom (AA), and coarse-grained (CG) molecular mechanics. In the first stage, we developed a rigorous AA CHARMM (Chemistry at Harvard Macromolecular Mechanics) force field (FF) for PEI on the basis of accurate ab initio calculations on protonated model pentamers. We validated this atomistic FF by matching the results of extensive molecular dynamics (MD) simulations of structural and dynamical properties of PEI with experimental data. In a second stage, we developed a CG MARTINI FF for PEI by Boltzmann inversion techniques from bead-based probability distributions obtained from AA simulations and ensuring an optimal match between the AA and CG structural and dynamical properties. In a third stage, we combined the developed CG FF for PEI with the standard MARTINI FF for DNA and performed comprehensive CG simulations of DNA-PEI complex formation and condensation. Various technical aspects which are crucial for the realistic modeling of DNA-PEI polyplexes, such as options of treating electrostatics and the relevance of polarizable water models, are discussed in detail. Massive CG simulations (with up to 500 000 beads) shed light on the mechanism and provide time scales for DNA polyplex formation independence of PEI chain size and protonation pattern. The DNA-PEI condensation mechanism is shown to primarily rely on the formation of DNA bundles, rather than by changes of the DNA-strand curvature. The gained insights are expected to be of significant help for designing effective gene-delivery applications.

Keywords: DNA condensation, gene-delivery, polyethylene-imine, molecular dynamics.

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Authors: Bhanupriya Sanger, Kiran Roat, Gayatri Swarnakar

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Helminths including Paramphistomum Cervi (P. cervi) are a major cause of reduced production in livestock or domestic ruminant. Rajasthan is the largest state of India having a maximum number of livestock. The economy of rural people largely depends on livestock such as cow, buffalo, goat and sheep. The prevalence of P. cervi helminth parasite is extremely high in buffalo (Bubalus bubalis) of Udaipur, which causes the disease paramphistomiasis. This disease mainly affects milk, meat, wool production and loss of life of buffalo. Chemotherapy is the only efficient and effective tool to cure and control the helminth P. cervi infection, as efficacious vaccines against helminth have not been developed so far. Various veterinary drugs like Albendazole have been used as the standard drug for eliminating P. cervi from buffalo, but these drugs are unaffordable and inaccessible for poor livestock farmers. The fruits, leaves and seeds of Clitoria ternatea Linn. are known for their ethno-medicinal value and commonly known as “Aprajita” in India. Seed extract of Clitoria ternatea found to have a significant anthelmintic action against Paramphistomum cervi at the dose of 35 mg/ml. The tegument of treated P. cervi was compared with controlled parasites by light microscopy. Treated P. cervi showed extensive distortion and destruction of the tegument including ruptured parenchymal cells, disruption of musculature cells, swelling and vacuolization in tegumental and sub tegumental cells. As a result, it can be concluded that the seeds of Clitoria ternatea can be used as the anthelmintic agent. Key words: Paramphistomiasis, Buffalo, Alcoholic extract, Paramphistomum cervi, Clitoria ternatea.

Keywords: buffalo, Clitoria ternatea, Paramphistomiasis, Paramphistomum cervi

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Authors: Mohamed Wahba

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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.

Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Abdulaziz Alnajem, Amit Sharma

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Business Case: Project delivery and enhancing activities' completion in the shortest possible time is critical during execution to proceed with the subsequent phases of Procurement, C & C phases of Contracts to have the required Production facilities/Infrastructure in place to achieve the Company strategic objective of 4.0 MBOPD oil production. SOR (Statement of requirement): Design and Engineering phase of Projects execution takes a long time. It is observed that, in most of the cases, company has crossed the Project Design Submittals review time as per the Contract/Company Standards, resulting into delays in projects completion, and cost impact to the company. Study Scope: Scope of the study covers the process from date of first submission of D & E documents by the contractor to final approval by the controlling team to proceed with the procurement of materials. This scope covers projects handled by the company’s project management teams and includes only the internal review process by the company.

Keywords: business management system, project management, oil and gas, analysis, improvement, design, delays

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Authors: Cui Li, Xu Yuping

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Based on the question of, "Are short video creators who are digital workers controlled by platform rules?" this study discusses the specific ways of platform rules control and the impact on short video creators. Based on the theory of digital labor, this paper adopts the method of in-depth interview and participant observation and chooses 24 producers of short video content of Tiktok to conduct in-depth interview. At the same time, through entering the short video creation field, the author carries on the four-month field investigation, obtains the creation process related data, and analyzes how the short video creator, as the digital labor, is controlled by the platform rule, as well as the creator in this process of compromise and resistance, a more comprehensive presentation of the short video creators of the labor process. It is found that the short video creators are controlled by the platform rules, mainly in the control of traffic rules, and the creators create content, compromise and resist under the guidance of traffic. First, while the platform seems to offer a flexible and autonomous way for creators to monetize, the threshold for participating in the event is actually very high for creators, and the rules for monetizing the event are vague. Under the influence of the flow rule, the creator is faced unstable incomes and high costs. Therefore, creators have to follow the rules of traffic to guide their own creation, began to flow-oriented content production, mainly reflected in the need to keep up-to-date, the pursuit of traffic to ride on the hot spots, in order to flow regardless, set up people "Born for the show", by the label solidified content creation. Secondly, the irregular working hours lead to the extension and overwork of the working hours, which leads to the internal friction of the short video creators at the spiritual level, and finally leads to the Rat Race of video creation. Thirdly, the video creator has completed the internalization and compromise of the platform rules in practice, which promotes the creator to continue to create independently, and forms the intrinsic motive force of the creator. Finally, the rule-controlled short video creators resist and fight in flexible ways, make use of the mechanism and rules of the platform to carry on the second creation, carry on the routine production, purchase the false flow, transfer the creation position to maintain own creation autonomy.

Keywords: short videos, tiktok, production, digital labors

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Authors: Vijay R. Patil, Sathiyanarayanan Lohidasan, K. R. Mahadik

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Gastrointestinal stability of andrographolide was evaluated in vitro in simulated gastric (SGF) and intestinal (SIF) fluids using a validated HPLC-PDA method. The method was validated using a 5μm ThermoHypersil GOLD C18column (250 mm × 4.0 mm) and mobile phase consisting of water: acetonitrile; 70: 30 (v/v) delivered isocratically at a flow rate of 1 mL/min with UV detection at 228 nm. Andrographolide in pure form and extract Andrographis paniculata was incubated at 37°C in an incubator shaker in USP simulated gastric and intestinal fluids with and without enzymes. Systematic protocol as per FDA Guidance System was followed for stability study and samples were assayed at 0, 15, 30 and 60 min intervals for gastric and at 0, 15, 30, 60 min, 1, 2 and 3 h for intestinal stability study. Also, the stability study was performed up to 24 h to see the degradation pattern in SGF and SIF (with enzyme and without enzyme). The developed method was found to be accurate, precise and robust. Andrographolide was found to be stable in SGF (pH ∼ 1.2) for 1h and SIF (pH 6.8) up to 3 h. The relative difference (RD) of amount of drug added and found at all time points was found to be < 3%. The present study suggests that drug loss in the gastrointestinal tract takes place may be by membrane permeation rather than a degradation process.

Keywords: andrographolide, Andrographis paniculata, in vitro, stability, gastric, Intestinal HPLC-PDA

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Authors: Rishabh Hans, Saksham Sharma

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Drying of a sessile droplet imbibed with colloidal solution is a complex process in many aspects. Till now, most of the work revolves around; conditions for buckling onset, post-buckling effects, nature of change of droplet shape etc. In this work, we are determining the shape of daughter cavity (DC) formed during post-buckling onset, a less explored stage, and its relationship with experimental parameters. We have introduced solid angle as a special parameter that can quantify the shape of DC at any instant. It facilitates us to compare the shape while experimenting across different substrate types, droplet sizes and particle concentration. Furthermore, the angular location of ‘weak spot’ on the periphery of droplet, which marks the initiation of cavity growth, varies in different conditions. To solve this problem, we have evaluated the deflection angle of weak spots w.r.t. the vertical axis going through the middle of droplet. Subsequently, the solid angle subtended by DC is analyzed about that inclined axis. Finally, results of analysis allude that increasing colloidal concentration has inverse effect on the growth rate of cavity’s shape. Moreover, the cap radius of DC is observed lower for high PLR which makes the capillary pressure higher and thus tougher to expedite cavity formation relatively. This analysis can be helpful in further studies to relate the shape, deflection angle, growth rate of daughter cavity to the type of droplet crust formed in the end. Examining DC stage shall add another layer to nano-colloidal research which aims to influence many industrial applications like patterning, coatings, drug delivery, food processing etc.

Keywords: buckling of sessile droplets, daughter cavity, droplet evaporation, nanoporous shell formation, solid angle

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Authors: Israel Ekanade, Richard Molapo, Patrick Dzimiri, Isaac Ndlovu

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This study aims to unravel the myth behind animosity towards foreign nationals in South Africa. Systemic violence against foreign African nationals since 2008 to date necessitates critical research with regards to migration issues connected to social upheavals. Extensive research ubiquitously tagged black-on-black violence as xenophobia or Afrophobia. In all, escalation of violence indicates a connotation of belonging. With unemployment rates approaching a crescendo, other vices have also soared in the same regard. As a result, this present generation seems cynical as the South African state has not fulfilled her obligations towards the indigent population; a situation pitching locals against foreigners. Locals have repeatedly blamed African foreign nationals for the economic downturn, using service delivery strikes to express their grievances. These strikes have continued unabatedly over the years but February 2017 marked a turning point in ‘insider-outsider’ relations as the strike was now turned to an anti-immigrant march resulting into widespread violence as the police failed to restore normalcy at some point. Over time, migration has been a harbinger of violence against the foreign black population in South Africa. Our paper encourages the state and civil society to invent new peace-building mechanisms to reduce xenophobic orchestrated violence. Our paper also contends that since the political class has hijacked the situation by using the youths for political propaganda during crises periods, a re-education of the political class and a culture of tolerance is inevitable for peace and harmony between locals and foreigners in post-apartheid South Africa.

Keywords: anti-immigrant march, politics of belonging, service delivery strikes, South Africa

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Authors: Pooja Pandey

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The role of communication plays an integral part in the management of any disaster, whether natural or human-induced, both require effective and strategic delivery of information. The way any information is conveyed carries the most weight while dealing with the disaster. Hence, integrating communication strategies in disaster risk management (DRM) are extensively acknowledged however, these integration and planning are missing from the practical books. Researchers are continuously exploring integrated DRM and have established substantial vents between research and implementation of the strategies (gaps between science and policy). For this reason, this paper reviews the communication barriers that obstruct effective management of the disaster. Communication between first responders (government agencies, police, medical services) and the public (people directly affected by the disaster) is most critical and lacks proper delivery during a disaster. And these challenges can only be resolved if the foundation of the problem is properly dealt with, which is resolving the issues within the organizations. Through this study, it was found that it is necessary to build the communication gap between the organizations themselves as most of the hindrances occur during the mitigation, preparedness, response and recovery phase of the disaster. The study is concluded with the main aim to review the communication barriers within and at the organizational, technological, and social levels that impact effective DRM. In the end, some suggestions are made to strengthen the knowledge for future improvement in communication between the responders and their organizations.

Keywords: communication, organization, barriers, first responders, disaster risk management

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Authors: Alison C. Essary, Victor Trastek

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Introduction: The current state of the health care system in the U.S. is characterized by an unprecedented number of people living with multiple chronic conditions, unsustainable rise in health care costs, inadequate access to care, and wide variation in health outcomes throughout the country. An estimated two-thirds of Americans are living with two or more chronic conditions, contributing to 75% of all health care spending. In 2013, the School for the Science of Health Care Delivery (SHCD) was charged with redesigning the health care system through education and research. Faculty in business, law, and public policy, and thought leaders in health care delivery, administration, public health and health IT created undergraduate, graduate, and executive academic programs to address this pressing need. Faculty and students work across disciplines, and with community partners and employers to improve care delivery and increase value for patients. Methods: Curricula apply content in health care administration and operations within the clinical context. Graduate modules are team-taught by faculty across academic units to model team-based practice. Seminars, team-based assignments, faculty mentoring, and applied projects are integral to student success. Cohort-driven models enhance networking and collaboration. This observational study evaluated two years of admissions data, and one year of graduate data to assess program outcomes and inform the current graduate-level curricula. Descriptive statistics includes means, percentages. Results: Fall 2013, the program received 51 applications. The mean GPA of the entering class of 37 students was 3.38. Ninety-seven percent of the fall 2013 cohort successfully completed the program (n=35). Sixty-six percent are currently employed in the health care industry (n=23). Of the remaining 12 graduates, two successfully matriculated to medical school; one works in the original field of study; four await results on the MCAT or DAT, and five were lost to follow up. Attrition of one student was attributed to non-academic reasons. Fall 2014, the program expanded to include both on-ground and online cohorts. Applications were evenly distributed between on-ground (n=70) and online (n=68). Thirty-eight students enrolled in the on-ground program. The mean GPA was 3.95. Ninety-five percent of students successfully completed the program (n=36). Thirty-six students enrolled in the online program. The mean GPA was 3.85. Graduate outcomes are pending. Discussion: Challenges include demographic variability between online and on-ground students; yet, both profiles are similar in that students intend to become change agents in the health care system. In the past two years, on-ground applications increased by 31%, persistence to graduation is > 95%, mean GPA is 3.67, graduates report admission to six U.S. medical schools, the Mayo Medical School integrates SHCD content within their curricula, and there is national interest in collaborating on industry and academic partnerships. This places SHCD at the forefront of developing innovative curricula in order to improve high-value, patient-centered care.

Keywords: delivery science, education, health care delivery, high-value care, innovation in education, patient-centered

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Authors: Zaka Nisa, Farooq Sher

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Adverse drug reactions (ADRs) underreporting is a great challenge to Pharmacovigilance. Health care professionals have to consider ADR reporting as their professional obligation, an effective system of ADR reporting is important to improve patient health care and safety. The present study is designed to assess the knowledge, attitude, practice and factors associated with ADR reporting by health care professionals (physicians and pharmacists) in public and private hospitals of Pakistan. A pretested questionnaire was administered to 384 physicians and pharmacists in public and private hospitals. Respondents were evaluated for their knowledge, attitude, and practice related to ADR reporting. The data was analyzed using the SPSS statistical software, the factors which encourage and discourage respondents in reporting ADRs were determined. Most of the respondents have shown a positive attitude towards ADR reporting. The response rate was 95.32%. Of the 367 questionnaires, including 333 (86.5%) physicians and 34 (8.8%) pharmacists with the mean age 28.34 (SD= 6.69), most of the respondents showed poor ADR reporting knowledge (83.1%). The majority of respondents (78.2%) showed positive attitude towards ADR reporting and only (12.3%) hospitals have good ADR reporting practice. Knowledge of respondents in public hospitals (8.6%) was less as compare to those in the private hospitals (29.7%) (P < 0.001). Attitude of respondents in private hospitals was more positive (92.4%) than those in public hospitals (68.8%) (P < 0.001). No significant difference was observed in practicing of ADR reporting in public (11.8%) and private hospitals (13.1%) (P value 0.89). Seriousness of ADR, unusualness of reaction, new drug involvement and confidence in diagnosis of ADR were the factors which encourage respondents to report ADR, however, lack of knowledge regarding where and how to report ADR, lack of access to ADR reporting form, managing patients was more important than reporting ADR, legal liability issues were the factors which discourage respondents to report ADR. The study reveals poor knowledge and practice regarding ADR reporting. However positive attitude was seen regarding ADR reporting. There is a need of educational training for health care professionals as well as genuine and continuous efforts are required by Government and health authorities to ensure the proper implementation of ADR reporting system in all of the hospitals.

Keywords: adverse drugs reactions (ADR), pharmacovigilance, spontaneous ADR reporting, knowledge of ADR, attitude of health care profesionals, practice of ADR reporting

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Authors: Huda Abdelrhman Osman Ahmed, Paul Feyi Waboso

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Introduction: Placenta accreta spectrum (PAS) disorders present a significant challenge in obstetric management due to the high risk of hemorrhage and potential complications at delivery. This case describes a 27+3 weeks gestation in a patient with placenta accreta managed with classical cesarean section and peripartum hysterectomy. Case Description: AGravida 4P3 patient presented at 27+3 weeks gestation with painless, unprovoked vaginal bleeding and an estimated blood loss (EBL) of 300 mL. At the 20+5 week anomaly scan, a placenta previa was identified anterior, covering the os anterior uterus and containing lacunae with signs of myometrial thinning. At a 24+1 week scan conducted at a tertiary center, further imaging indicated placenta increta with invasion into the myometrium and potential areas of placenta percreta. The patient’s past obstetric history included three previous cesarean sections, with no significant medical or surgical history. Social history revealed heavy smoking but no alcohol use. No drug allergies were reported. Given the risks associated with PAS, a management plan was formulated, including an MRI at a later stage and cesarean delivery with a possible hysterectomy between 34-36 weeks. However, at 27+3 weeks, the patient experienced another episode of vaginal bleeding EBL 500 ml, necessitating immediate intervention. Management: As the patient was unstable, she was not transferred to the tertiary center. Completed and informed consent was obtained. MDT planning-group and cross-matching 4 units, uterotonics. Tranexamic acid blood products, cryo, cell salvage, 2 obstetric consultants and an anesthetic consultant, blood bank aware and hematologist. HDU bed and ITU availability. This study assisted in performing a classical Caesarean section, Where the urologist inserted JJ ureteric stents. Following this, we also assisted in a total abdominal hysterectomy with the conservation of ovaries. 4 units RBC and 1 unit FFP were transfused. The total blood loss was 2.3 L. Outcome: The procedure successfully achieved hemostasis, and the neonate was delivered with subsequent transfer to a neonatal intensive care unit for management. The patient’s postoperative course was monitored closely with no immediate complications. Discussion: This case highlights the complexity and urgency in managing placenta accreta spectrum disorders, particularly with the added challenges posed by remote location and limited tertiary support. The need for rapid decision-making and interdisciplinary coordination is emphasized in such high-risk obstetric cases. The case also underscores the potential for surgical intervention and the importance of family involvement in emergent care decisions. Conclusion: Placenta accreta spectrum disorders demand meticulous planning and timely intervention. This case contributes to understanding PAS management at earlier gestational ages and provides insights into the challenges posed by access to tertiary care, especially in urgent situations.

Keywords: Accreta, Hysterectomy, 3MDT, prematurity

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Authors: Swathi Gopakumar, Sruthi Krishna, Shivasubramani Krishnamoorthy

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Contactless, painless and radiation-free thermal imaging technology is one of the preferred screening modalities for detection of breast cancer. However, poor signal to noise ratio and the inexorable need to preserve edges defining cancer cells and normal cells, make the segmentation process difficult and hence unsuitable for computer-aided diagnosis of breast cancer. This paper presents key findings from a research conducted on the appraisal of two promising techniques, for the detection of breast cancer: (I) marker-controlled, Level-set segmentation of anisotropic diffusion filtered preprocessed image versus (II) Segmentation using marker-controlled level-set on a Gaussian-filtered image. Gaussian-filtering processes the image uniformly, whereas anisotropic filtering processes only in specific areas of a thermographic image. The pre-processed (Gaussian-filtered and anisotropic-filtered) images of breast samples were then applied for segmentation. The segmentation of breast starts with initial level-set function. In this study, marker refers to the position of the image to which initial level-set function is applied. The markers are generally placed on the left and right side of the breast, which may vary with the breast size. The proposed method was carried out on images from an online database with samples collected from women of varying breast characteristics. It was observed that the breast was able to be segmented out from the background by adjustment of the markers. From the results, it was observed that as a pre-processing technique, anisotropic filtering with level-set segmentation, preserved the edges more effectively than Gaussian filtering. Segmented image, by application of anisotropic filtering was found to be more suitable for feature extraction, enabling automated computer-aided diagnosis of breast cancer.

Keywords: anisotropic diffusion, breast, Gaussian, level-set, thermograms

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Authors: Harihara Subramaniam Salem Chandrasekaran

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Scrum framework is built upon emphasises on self-management and cross-functionality around which the framework is built upon. However, in reality, many organisations that adapt scrum are having functional structures and hierarchy. In such cases, the scrum teams are built with a mixture of people from different functionalities to deliver specific products and projects. For instance, every scrum team would be having a designer, developer or tester, etc.; who will make their own contribution to an increment. This results in people centric dependencies for delivering an increment and thus creating bottlenecks at certain times. This paper presents in detail how functional silos are a challenge to the scrum teams and hinder the incremental deliver of value to customers. The study has been conducted with 14 individuals from the software industry from different functional departments, and the findings summarize that functional silos are naturally formed due to the organizational dynamics and hierarchy and the mindset of being confined within the silos is detrimental to the fundamental values of agile and scrum. The paper also sheds light on what the individuals propose to overcome the silo mindset within the scrum team and focus on continuous improvement in delivery excellence.

Keywords: agile, scrum, cross-functional, functional silos

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Authors: Jiwan P. Lavande, A. V. Chandewar

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In the present study, orodispersible tablets of diphenhydramine hydrochloride were prepared using croscarmellose sodium, crospovidone and camphor, menthol (as subliming agents) in different ratios and ODTs prepared with superdisintegrants were compared with ODTs prepared with camphor and menthol (subliming agents) for the following evaluation of in vitro disintegration time, dispersion time, wetting time, hardness and water absorption ratio. Results revealed that the tablets of all formulations have acceptable physical parameters. The drug and excipients compatibility study was evaluated using FTIR technique and has not detected any incompatibility. The in vitro release of drug from DC6 formulation was quick when compared to other formulations. Stability study was carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets had not shown any significant difference. Microscopic study of different formulations of sublimed tablets showed formation of pores for the tablets prepared by sublimation method. Thus, conclusion can be made that the stable orodispersible tablets of diphenhydramine hydrochloride can be developed for the rapid release of diphenhydramine hydrochloride.

Keywords: orodispersible tablet, subliming agent, super disintegrants, diphenhydramine hydrochloride

Procedia PDF Downloads 235