Doctor of Philosophy

dissertationFemale-controlled preventative technologies are being developed to decrease HIV sexual transmission rates in resource poor regions of the world where the pandemic is most prevalent. Intravaginal rings (IVRs) comprise extended duration vaginal drug delivery vehicles which may provide sustained release of antiretrovirals at local inhibitory concentrations to prevent initial HIV infection during coitus. Few IVR formulations have been researched for HIV prophylaxis although numerous antiretrovirals are excellent candidates. Poor progress is due in part to limitations of conventional IVR technology in delivering antiretrovirals with diverse physiochemical properties and dosing requirements. Furthermore, there is limited understanding of drug vaginal pharmacokinetics and potential toxicological effects on the local environment. Consequently, in this dissertation several candidate antiretrovirals were formulated in new IVR platforms and animal models were developed to characterize the IVR formulations in vivo. In the first part of the dissertation, polyurethane IVRs were designed that delivered the potent and dual-acting pyrimidinedione congeners for up to one month. The pyrimidinediones attained concentrations throughout the nonhuman primate vaginal tract that were expected to be inhibitory against HIV, with no observed detrimental effects to the vaginal environment. In the second part of the dissertation, an IVR was developed to simultaneously deliver dapivirine and tenofovir which possess contrasting hydrophilicity and differing mechanisms of action against HIV. A two segment ring design was utilized which independently optimized tenofovir and dapivirine release by using compositionally different polyurethanes. In the final two parts of the dissertation, a hydrophilic polyurethane reservoir IVR was engineered and tested in a new sheep model, whereby tenofovir vaginal concentrations from the IVR were similar to the clinically effective tenofovir vaginal gel but for 90 day duration. The tunable IVR platform allowed for achievement of desired drug release rates and ring mechanical stiffness which were time-independent. No major toxicological effects were observed in sheep, and extensive IVR in vitro characterization was performed to ensure that a chemically and physically stabilized product was achieved. The work reported herein describes the design and characterization of antiretroviral-eluting intravaginal rings which each hold promise as preventative technologies to prevent the sexual transmission of HIV

Intersectoral Convergence and ICTs: Integrated ICT Approaches to Rural Poverty Reduction

As reforms have paved the way for India’s rapid economic expansion in recent years, particularly in the service sector, Information and Communications Technology (ICT) has assumed a dominant role as the underwriter of India’s growth. Outside of the commercial applications where ICT has been most extensively applied so far, ICT also holds great potential to drive human development, narrowing gaps between the rich and the poor as well as rural and urban areas. In many development-adjacent sectors, particularly education, agriculture, and health, platforms and initiatives have already demonstrated ICT’s promise as a transformational suite of technologies which democratize information and dramatically reduce transaction costs. However, even greater progress is possible if initiatives apply an intersectoral approach which applies best practices from other sectors, highlights synergies between sectors, and identifies pitfalls stemming from hidden competition of priorities between sectors that could otherwise derail a project. Intersectoral analysis also recognizes how advances in the sectors under study contribute to growth in the broader economy. By applying an intersectoral lens, individual programs can be strengthened, new opportunities can be identified, and ICT can be more thoroughly woven into a tapestry that benefits all aspects of people’s lives. ICT-driven development has not entirely ignored intersectorality, but opportunities abound for improving these initiatives by applying a more holistic lens. In particular, the field of nutrition is most sorely in need of mainstreaming within the many different siloed development objectives that touch upon it. Data, the foundation of ICT, provides great opportunities for refining programs of all types, but also carries great risks to privacy and potentially social equality. And untapped synergies exist between the cutting-edge advances in the Education sector and educational initiatives in other sectors which have not benefited from the same intentional pedagogical design

Microbicides 2006 conference

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23–26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities

Doctor of Philosophy

dissertationOver three decades have passed since the discovery of human immunodeficiency virus (HIV), and with no viable vaccine, new technologies to prevent the spread of the virus are urgently needed. Pre-exposure prophylaxis, the concept of chemically interrupting HIV transmission, effectively reduced HIV incidence in a number of clinical trials. However, it has been difficult to achieve high and consistent effectiveness in clinical trials due to variable adherence to the dosing regimens requiring frequent administration. This, along with the disproportionate burden of the HIV/AIDS pandemic in young women in sub- Saharan Africa, has catalyzed the research into long-acting, antiretroviral eluting drug delivery systems like intravaginal rings (IVR) in an attempt to increase adherence over dosage forms that require frequent administration, and provide a more consistent drug concentration where transmission occurs. However, IVR technology is generally limited to releasing small quantities of hydrophobic, low molecular weight species that can diffuse through the IVR elastomer. This dissertation describes two adaptable drug delivery platforms that increased the diversity of the drugs that can be delivered from IVRs. Polyether urethane reservoir IVRs were engineered for the delivery of the thermally and hydrolytically unstable prodrug tenofovir disoproxil fumarate. This drug presents a unique design challenge to minimize the hydrolytic drug degradation in the IVR core while also promoting hydration to solubilize and release the drug. This design delivered mg/day quantities of drug and conferred complete protection in macaques from multiple vaginal viral exposures. Next, we engineered a system that uncouples the mechanism of drug release from the interaction of the drug with the elastomer and provides nearly constant release of any stable molecule. In this system, orifices control the hydration rate of the hydrophilic matrix contained within the core of the IVR, and release of the drug-containing gel. We evaluated the utility of this system for the topical delivery of macromolecules, and multiple different small molecule antiretrovirals, specifically for the delivery of drug microparticles. This work describes the design and evaluation of antiretroviral eluting IVR systems that provide adaptable platforms for vaginal drug delivery

A review of natural language processing in contact centre automation

Contact centres have been highly valued by organizations for a long time. However, the COVID-19 pandemic has highlighted their critical importance in ensuring business continuity, economic activity, and quality customer support. The pandemic has led to an increase in customer inquiries related to payment extensions, cancellations, and stock inquiries, each with varying degrees of urgency. To address this challenge, organizations have taken the opportunity to re-evaluate the function of contact centres and explore innovative solutions. Next-generation platforms that incorporate machine learning techniques and natural language processing, such as self-service voice portals and chatbots, are being implemented to enhance customer service. These platforms offer robust features that equip customer agents with the necessary tools to provide exceptional customer support. Through an extensive review of existing literature, this paper aims to uncover research gaps and explore the advantages of transitioning to a contact centre that utilizes natural language solutions as the norm. Additionally, we will examine the major challenges faced by contact centre organizations and offer reco

The Democratization of Artificial Intelligence: Net Politics in the Era of Learning Algorithms

After a long time of neglect, Artificial Intelligence is once again at the center of most of our political, economic, and socio-cultural debates. Recent advances in the field of Artifical Neural Networks have led to a renaissance of dystopian and utopian speculations on an AI-rendered future. Algorithmic technologies are deployed for identifying potential terrorists through vast surveillance networks, for producing sentencing guidelines and recidivism risk profiles in criminal justice systems, for demographic and psychographic targeting of bodies for advertising or propaganda, and more generally for automating the analysis of language, text, and images. Against this background, the aim of this book is to discuss the heterogenous conditions, implications, and effects of modern AI and Internet technologies in terms of their political dimension: What does it mean to critically investigate efforts of net politics in the age of machine learning algorithms

The Democratization of Artificial Intelligence

After a long time of neglect, Artificial Intelligence is once again at the center of most of our political, economic, and socio-cultural debates. Recent advances in the field of Artifical Neural Networks have led to a renaissance of dystopian and utopian speculations on an AI-rendered future. Algorithmic technologies are deployed for identifying potential terrorists through vast surveillance networks, for producing sentencing guidelines and recidivism risk profiles in criminal justice systems, for demographic and psychographic targeting of bodies for advertising or propaganda, and more generally for automating the analysis of language, text, and images. Against this background, the aim of this book is to discuss the heterogenous conditions, implications, and effects of modern AI and Internet technologies in terms of their political dimension: What does it mean to critically investigate efforts of net politics in the age of machine learning algorithms

Blockchain and Internet of Things in smart cities and drug supply management: Open issues, opportunities, and future directions

Blockchain-based drug supply management (DSM) requires powerful security and privacy procedures for high-level authentication, interoperability, and medical record sharing. Researchers have shown a surprising interest in Internet of Things (IoT)-based smart cities in recent years. By providing a variety of intelligent applications, such as intelligent transportation, industry 4.0, and smart financing, smart cities (SC) can improve the quality of life for their residents. Blockchain technology (BCT) can allow SC to offer a higher standard of security by keeping track of transactions in an immutable, secure, decentralized, and transparent distributed ledger. The goal of this study is to systematically explore the current state of research surrounding cutting-edge technologies, particularly the deployment of BCT and the IoT in DSM and SC. In this study, the defined keywords “blockchain”, “IoT”, drug supply management”, “healthcare”, and “smart cities” as well as their variations were used to conduct a systematic search of all relevant research articles that were collected from several databases such as Science Direct, JStor, Taylor & Francis, Sage, Emerald insight, IEEE, INFORMS, MDPI, ACM, Web of Science, and Google Scholar. The final collection of papers on the use of BCT and IoT in DSM and SC is organized into three categories. The first category contains articles about the development and design of DSM and SC applications that incorporate BCT and IoT, such as new architecture, system designs, frameworks, models, and algorithms. Studies that investigated the use of BCT and IoT in the DSM and SC make up the second category of research. The third category is comprised of review articles regarding the incorporation of BCT and IoT into DSM and SC-based applications. Furthermore, this paper identifies various motives for using BCT and IoT in DSM and SC, as well as open problems and makes recommendations. The current study contributes to the existing body of knowledge by offering a complete review of potential alternatives and finding areas where further research is needed. As a consequence of this, researchers are presented with intriguing potential to further create decentralized DSM and SC apps as a result of a comprehensive discussion of the relevance of BCT and its implementation.© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

The Democratization of Artificial Intelligence

After a long time of neglect, Artificial Intelligence is once again at the center of most of our political, economic, and socio-cultural debates. Recent advances in the field of Artifical Neural Networks have led to a renaissance of dystopian and utopian speculations on an AI-rendered future. Algorithmic technologies are deployed for identifying potential terrorists through vast surveillance networks, for producing sentencing guidelines and recidivism risk profiles in criminal justice systems, for demographic and psychographic targeting of bodies for advertising or propaganda, and more generally for automating the analysis of language, text, and images. Against this background, the aim of this book is to discuss the heterogenous conditions, implications, and effects of modern AI and Internet technologies in terms of their political dimension: What does it mean to critically investigate efforts of net politics in the age of machine learning algorithms

PREFORMULATION AND BIOLOGICAL EVALUATIONS FOR THE INTRAVAGINAL DELIVERY OF GRIFFITHSIN FOR HIV PREVENTION

HIV/AIDS persists as a global health concern, with the overwhelming majority of infections caused by sexual transmission. The lack of effective prevention modalities for women has prompted research of novel approaches to prevent disease spread. One such approach includes vaginal microbicides. The work presented within this dissertation project contributes significantly to the vaginal microbicide field, focusing on preformulation assessments, stability in the biological environment, and drug targeting of the biopharmaceutical microbicide candidate Griffithsin (GRFT). We hypothesized that GRFT will undergo physical and chemical instabilities that will affect successful formulation and vaginal delivery of this microbicide candidate. We further hypothesized that GRFT will undergo binding interactions within cervicovaginal secretions that will negatively impacting GRFT-gp120 binding and that GRFT will not be able to inhibit HIV binding to the DC-SIGN receptor and transfer to CD4 cells because GRFT will not permeate cervical tissue. Identification of degradation pathways for GRFT was conducted by performing preformulation experiments under selected conditions of temperature, light, shear, ionic strength, and oxidation. Analytical methods included HPLC, CD, UV-spectroscopy, ELISA, and SDS-PAGE. GRFT chemical modifications, including intact mass analyses and peptide sequencing, were evaluated in the presence of hydrogen peroxide and human cervicovaginal secretions. The effects of human cervicovaginal secretions on GRFT-gp120 binding was also assessed with ELISA. Tissue permeability and localization of GRFT was evaluated using excised human ectocervical tissue. Major findings from this dissertation indicate that: (1) GRFT is prone to oxidation, by both hydrogen peroxide exposure and human cervicovaginal secretion exposure; (2) Methionine at position 78 in the amino acid sequence of GRFT is oxidized; (3) GRFT-gp120 binding is inhibited in human cervicovaginal secretions containing normal microflora, but not in secretions with BV; and (4) GRFT does not permeate deep into or through human cervical tissue, but does adheres to the superficial epithelial tissue. Overall, this dissertation has created more knowledge about a drug candidate in the microbicide field and will guide further development of GRFT. Further, the methodologies implemented throughout this dissertation can be used or adapted as part of a strategy to preclinically evaluate other vaginal microbicide candidates