Electrospinning nanofiber insert for anterior ocular drug delivery for cataract treatment : A thesis submitted in partial fulfilment of the requirements for the Degree of Doctor of Philosophy at Lincoln University

The eye is a complex visual aid (for human and animals) which gathers visual information from the surrounding physical environment. The more common vision threatening diseases that affect both anterior/posterior segment (age related macular degeneration, cataract, keratitis, glaucoma, diabetic retinopathy, retinoblastoma, allergic conjunctivitis, and ocular trauma) is a massive social and economic burden especially for less developed countries. Drug delivery to any tissue is a challenge, eye is not an exception. Barriers to ocular drug delivery are both physiological, anatomical, static, and dynamic. The current cost-effective cataract treatment option involves surgical removal of opaque or cataractous lens and replicated with artificial intraocular lens followed with topical application of corticosteroid eye drops as post-operative management. Whilst current topical drugs are easy to apply their bioavailability is impeded due to various barriers prevailing in the eye which put a strain on the cost and the duration of recovery. This has led researchers to the path of finding alternative methods of ocular drug delivery which more recently has led to the use of nanotechnology. Nanotechnology research that can transport and deliver active ingredient (AI) safely to site of action has gained importance in recent years. Ocular drug delivery with nanotechnology though can overcome some of the challenges but does have some limitations, like patient compliance and irritation. These limitations have been addressed by researchers across the globe by reducing drug particle size, using less irritable polymers and excipients, but with limited success. The research presented in this thesis approached this problem using nanofiber technology to develop solid ocular insert that would allow sustained drug delivery. Caffeine, a model drug, was used to determine the kinetics of bioactive release. Nanofiber membranes fabricated as mono-, two- or three-layered using two polymers, poly (ethylene) oxide (PEO) and poly ε-caprolactone (PCL) and analysed for physical characteristics of fiber (mat thickness, water contact angle, tensile properties, SEM) and drug release. Results from this study shows that the thickness of mat can be increased by having additional layer (average of 46% for two- and 54% for three-layered) compared to monolayer but it is not proportionate to the extra amount of polymer. For water contact angle the results achieved for various iterations were on par with the property of the polymer, hydrophobicity (>80°) and hydrophilicity (<50°). The tensile properties (only for mono- and three-layered formulation), puncture strength and elongation at break there was no differences between the formulations for elongation at break but for puncture strength, the force required was almost double for three-layered formulation compared to control monolayer. However, it was a challenge to measure the tensile property for monolayer formulation with PEO polymer. Mucoadhesion evaluated for only three-layered nanofiber formulations containing PEO and PCL polymer shows that the force required to detach the mat from mucin tablet (used as test material) was almost double compared to the monolayer control formulations. Surface morphology (SEM) of the nanofiber mat shows heterogenous fiber diameter distribution irrespective of the polymer and number of layers. The caffeine release from monolayer was almost immediate (within 5 min) for the formulations with PEO polymer (>50%) compared to PCL polymer wherein the same release % was noticed 1h after the initiation of the experiment. The drug release from two-layered formulation was reduced by 50% when the drug was incorporated in the first layer and the second layer acted as a barrier. Unlike the two-layered formulation, same results could not be achieved from a three-layered formulation when the drug was incorporated in the third layer, there was average >70% drug released after 1h. Surface morphology of mono- and three-layered formulations exhibited the presence of caffeine crystalline structures on the surface of the fiber which probably has attributed to immediate burst release of the drug when in contact with the aqueous solution. The results from this study elucidate that mucoadhesion onto the cornea surface can be enhanced by incorporating a hydrophilic polymer into the formulation which would probably help in the retention and increase the bioavailability of the drug to the target site in the eye. The results also shows that burst release can be mitigated and sustained release achieved when there is a barrier layer to the drug as shown in the two-layered formulation where the drug release was reduced by 50% by having a barrier layer with only the hydrophobic polymer. This formulation show promise for bioactive delivery but will require further exploration and refining

Multimodal Sentiment Sensing and Emotion Recognition Based on Cognitive Computing Using Hidden Markov Model with Extreme Learning Machine

In today's competitive business environment, exponential increase of multimodal content results in a massive amount of shapeless data. Big data that is unstructured has no specific format or organisation and can take any form, including text, audio, photos, and video. Many assumptions and algorithms are generally required to recognize different emotions as per literature survey, and the main focus for emotion recognition is based on single modality, such as voice, facial expression and bio signals. This paper proposed the novel technique in multimodal sentiment sensing with emotion recognition using artificial intelligence technique. Here the audio and visual data has been collected based on social media review and classified using hidden Markov model based extreme learning machine (HMM_ExLM). The features are trained using this method. Simultaneously, these speech emotional traits are suitably maximised. The strategy of splitting areas is employed in the research for expression photographs and various weights are provided to each area to extract information. Speech as well as facial expression data are then merged using decision level fusion and speech properties of each expression in region of face are utilized to categorize. Findings of experiments show that combining features of speech and expression boosts effect greatly when compared to using either speech or expression alone. In terms of accuracy, recall, precision, and optimization level, a parametric comparison was made

Simulation and Integrated Testing of Process Models of PFBR Operator Training Simulator

AbstractHigh fidelity Full Scope Operator Training Simulators play a key role in imparting plant related knowledge to the operating personnel in an effective way. It provides a platform for training the operators on normal and emergency conditions including all types of scenarios that would arise in any Nuclear Power Plant. The scenario based training helps the plant operator to handle a crisis in an efficient manner with the ultimate goal of safe and efficient operation of the plant.This paper discusses about the general description of PFBR Operator Training Simulator, modeling and simulation of various process models, the complexities involved etc. It also covers the associated process logics, controls, display of alarms and indications, malfunctions and transient incidents related to each process model, integration with other sub systems, individual process model testing, integrated performance testing and verification and validation of models. Simulation of process models are broadly classified into two main categories namely, External Models - that are developed in-house and ported to the simulator environment and Internal Models - that are developed using Simulation Tool. External Models are tested on the desk top for intended functioning and after obtaining satisfactory results, the models are ported to the simulator base wherein the Logical and Virtual Panel Models are built to represent a real system of the plant. Internal Models are built using the Simulation Tools and integrated with the External Models after testing. Combination of External and Internal Model represents the total plant and the performance testing is conducted in an Integrated Mode to qua lify the Process Models for training purpose

Evaluation of the Parasight Platform for Malaria Diagnosis

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site

Production of microsclerotia from entomopathogenic fungi and use in maize seed coating as delivery for biocontrol against Fusarium graminearum

The commercial use of the entomopathogenic fungi Metarhizium spp. in biopesticides has gained more interest since the discovery that several species of this genus are able to colonize roots. In general, commercial products with Metarhizium are formulated based on conidia for insect pest control. The process of mass production, harvesting, and formulation of infective conidia can be detrimental for conidial viability. Entomopathogenic fungi such as Metarhizium spp. are able to produce high concentrations of resistant structures, known as microsclerotia, when grown in liquid media. Microsclerotia are desiccation tolerant, with excellent storage stability, and are capable of producing high quantities of infective conidia after rehydration. The aim of this study was to evaluate microsclerotia production by different isolates of Metarhizium spp. and determine the effect of microsclerotia coated onto maize seeds on plant growth in the presence of soil-borne pathogen Fusarium graminearum. On average, ~1 × 10⁵ microsclerotia/mL were produced by selected isolates of M. anisopliae (A1080 and F672) and Metarhizium robertsii (F447). Microsclerotia were formulated as granules with diatomaceous earth and used for seed coating, after which propagules produced around 5 × 10⁶ CFU/g of seeds. In the presence of the plant pathogen, maize plants grown from untreated seeds had the lowest growth, while plants treated with the Metarhizium microsclerotia had significantly greater growth than the control plants. Hyphae were observed growing on and in root tissues in all the Metarhizium spp. treatments but not in samples from control plants. Metarhizium hyphal penetration points' on roots were observed 1 month after sowing, indicating the fungi were colonizing roots as endophytes. The results obtained indicate that microsclerotia can be coated onto seeds, providing plant protection against soil plant pathogens and a method to establish Metarhizium in the ecto- and endo-rhizosphere of maize roots, allowing the persistence of this biocontrol agent

Case report: Bordetella holmesii: A rare pathogen causing infective endocarditis associated glomerulonephritis

Infective endocarditis (IE) can cause multiorgan dysfunction and chronic kidney disease, in addition to cardiac sequelae. The presentation may be vague and can manifest as acute glomerulonephritis. While the most common pathogens of infective endocarditis are Staphylococcus and Streptococcus species, we report a rare pathogen Bordetella holmesii causing infective endocarditis associated glomerulonephritis. A 20-year-old male patient with tetralogy of Fallot with pulmonary atresia and aortopulmonary collaterals underwent several cardiac surgeries including prosthetic pulmonary valve replacement in the past. He was admitted for 3 days at an outside hospital for fever, cough, and hemoptysis, and diagnosed with streptococcal pharyngitis, for which he received antibiotics. Five weeks later, he presented to our institution with lower extremity edema and gross hematuria. On examination, he was afebrile, normotensive, had a 7-kg weight gain with anasarca, and a systolic murmur, without rash. Investigations revealed elevated serum creatinine, nephrotic range proteinuria, hematuria, and hypocomplementemia, consistent with acute glomerulonephritis. Given his cardiac history, blood cultures were collected from three sites. Broad-spectrum antibiotics were initiated when he subsequently developed fever. Renal pathology on biopsy showed diffuse proliferative immune complex-mediated glomerulonephritis. Transesophageal echocardiogram visualized a vegetation on the pulmonary valve. Bordetella holmesii was ultimately cultured from the prior and current hospitalization. A serum sample detecting microbial cell-free DNA sequencing confirmed Bordetella holmesii at very high levels. After completing 6 weeks of intravenous antibiotics with concurrent angiotensin receptor blockade, his kidney function recovered with improvement in hypocomplementemia and proteinuria. This case report highlights the early recognition and comprehensive evaluation of a rare organism causing IE-associated GN, which allowed for renal recovery and preserved cardiac function