Formal description techniques for distributed computing systems:the challenges for the 1990's

Initially FDTs where developed within IS0 and CCITT for specification, at a high-level of abstraction, of distributed systems. Research is now being performed on the use of FDTs to support the complete implementation trajectory. In this paper we discuss a number of such research activities that are conducted within the framework of the Lotosphere project(*). The paper discusses aspects of design methodology, correctness preserving transformation, the reflection of design criteria, the role of pre-defined specification and implementation constructs, and formal approaches to conformance testing. Furthermore some insight is given in the development of a comprehensive toolset that supports these aspects of design methodology. The paper concludes with some experience obtained from the application of these methods and tools to some realistic pilot implementations: an ISDN and MHS application and a Transaction Processing application

Computer-aided approaches in drug design: the exigent way forward: dynamic perspectives into the mechanistic activities of small molecule inhibitors toward antiviral, antitubercular and anticancer therapeutic interventions.

Doctoral Degree. University of KwaZulu-Natal, Durban.The crucial role of CADD in the drug design process is now indisputable and has proven over the years that it can accelerate the discovery potential drug candidates while reducing the associated cost. Using knowledge and information about biological target or knowledge about a ligand with proven bioactivity, CADD, and its techniques can influence various drug discovery pipeline stages. The ability CADD approaches to elucidate drug-target interactions at the atomistic level allows for investigations of the mechanism of drugs' actions, revealing atomistic insights that influence drug design and improvement. CADD approaches also seek to augment traditional in vitro and in vivo experimental techniques and not replace them since CADD approaches can also allow modeling complex biological processes that hitherto seemed impossible to explore using experimental methods. According to the World Health Organization (WHO), featuring prominently in the top ten causes of death are cancer, lower respiratory tract infection, tuberculosis (TB), and viral infections such as HIV/AIDS. Collectively, these diseases are of global health concerns, considering a large number of associated deaths yearly. Over the years, several therapeutic interventions have been employed to treat, manage, or cure these diseases, including chemotherapy, surgery, and radiotherapy. Of these options, small molecule inhibitors have constituted an integral component in chemotherapy, thereby undoubtedly playing an essential role in patient management. Although significant success has been achieved using existing therapeutic approaches, the emergence of drug resistance and the challenges of associated adverse side effects has prompted the need for the drug design processes against these diseases to remain innovative, including combining existing drugs and establishing improved therapeutic options that could overcome resistance while maintaining minimal side effects to patients. Therefore, an exploration of drug target interactions towards unraveling mechanisms of actions as performed in the reports in this thesis are relevant since the molecular mechanism provided could form the basis for the design and identification of new therapeutic agents, improvement of the therapeutic activity of existing drugs, and also aid in the development of novel therapeutic strategies against these diseases of global health concern. Therefore the studies in this thesis employed CADD approaches to investigates molecular mechanisms of actions of novel therapeutic strategies directed towards some crucial therapeutics implicated in viral infections, tuberculosis, and cancer. Therapeutic targets studied included; SARS-CoV-2 RNA dependent RNA polymerase (SARS-CoV-2 RdRp), Human Rhinovirus B14 (HRV-B14) and human N-myristoyltransferases in viral infections, Dihydrofolate reductase (DHFR) and Flavin-dependent thymidylate synthase (FDTS) in TB, human variants of TCRCD1d, and Protein Tyrosine Phosphatase Receptor Zeta (PTPRZ) in cancer. The studies in this thesis is divided into three domains and begins with a thorough review of the concept of druggability and drug-likeness since the crux of the subsequent reports revolved around therapeutic targets and their inhibitions by small molecule inhibitors. This review highlights the principles of druggability and drug-likeness while detailing the recent advancements in drug discovery. The review concludes by presenting the different computational, highlighting their reliability for predictive analysis. In the first domain of the research, we sought to unravel the inhibitory mechanism of some small molecule inhibitors against some therapeutic targets in viral infections by explicitly focusing on the therapeutic targets; SARS-CoV-2 RdRp, HRV-B14, and N-myristoyltransferase. Therapeutic targeting of SARS-CoV-2 RdRp has been extensively explored as a viable approach in the treatment of COVID-19. By examining the binding mechanism of Remdesivir, which hitherto was unclear, this study sought to unravel the structural and conformational implications on SARS-CoV-2 RdRp and subsequently identify crucial pharmacophoric moieties of Remdesivir required for its inhibitory potency. Computational analysis showed that the modulatory activity of Remdesivir is characterized by an extensive array of high-affinity and consistent molecular interactions with specific active site residues that anchor Remdemsivir within the binding pocket for efficient binding. Results also showed that Remdesivir binding induces minimal individual amino acid perturbations, subtly interferes with deviations of C-α atoms, and restricts the systematic transition of SARS-CoV-2 RdRp from the “buried” hydrophobic region to the “surface exposed” hydrophilic region. Based on observed high-affinity interactions with SARS-CoV-2 RdRp, a pharmacophore model was generated, which showcased the crucial functional moieties of Remdesivir. The pharmacophore was subsequently employed for virtual screening to identify potential inhibitors of SARS-CoV-2 RdRp. The structural insights and the optimized pharmacophoric model provided would augment the design of improved analogs of Remdesivir that could expand treatment options for COVID-19. The next study sought to explore the therapeutic targeting of human rhinoviruses (HRV) amidst challenges associated with the existence of a wide variety of HRV serotypes. By employing advanced computational techniques, the molecular mechanism of inhibition of a novel benzothiophene derivative that reportedly binds HRV-B14 was investigated. An analysis of the residue-residue interaction profile revealed of HRV upon the benzothiophene derivative binding revealed a distortion of the hitherto compacted and extensively networked HRV structure. This was evidenced by the fewer inter-residue hydrogen bonds, reduced van der Waals interactions, and increased residue flexibility. However, a decrease in the north-south wall's flexibility around the canyon region also suggested that the benzothiophene derivative's binding impedes the “breathing motion” of HRV-B14; hence its inhibition. The next study in the first domain of the research investigated the structural and molecular mechanisms of action associated with the dual inhibitory activity of IMP-1088. This novel compound reportedly inhibits human N-myristoyltransferase subtypes 1 and 2 towards common cold therapy. This is because it has emerged that the pharmacological inhibition of Nmyristoyltransferase is an efficient non-cytotoxic strategy to completely thwart the replication process of rhinovirus toward common cold treatment. Using augmentative computational and nanosecond-based analyses, findings of the study revealed that the steady and consistent interactions of IMP-1088 with specific residues; Tyr296, Phe190, Tyr420, Leu453, Gln496, Val181, Leu474, Glu182, and Asn246, shared within the binding pockets of both HNMT subtypes, in addition to peculiar structural changes account for its dual inhibitory potency. Findings thus unveiled atomistic and structural perspectives that could form the basis for designing novel dualacting inhibitors of N-myristoyltransferase towards common cold therapy. In the second domain of the research, the mechanism of action of some small molecule inhibitors against DHFR, FDTS, and Mtb ATP synthase in treating tuberculosis is extensively investigated and reportedly subsequently. To begin with, the dual therapeutic targeting of crucial enzymes in the folate biosynthetic pathway was explored towards developing novel treatment methods for TB. Therefore, the study investigated the molecular mechanisms and structural dynamics associated with dual inhibitory activity of PAS-M against both DHFR and FDTS, which hitherto was unclear. MD simulations revealed that PAS-M binding towards DHFR and FDTS is characterized by a recurrence of strong conventional hydrogen bond interactions between a peculiar site residue the 2-aminov decahydropteridin-4-ol group of PAS-M. Structural dynamics of the bound complexes of both enzymes revealed that, upon binding, PAS-M is anchored at the entrance of hydrophobic pockets by a strong hydrogen bond interaction while the rest of the structure gains access to deeper hydrophobic residues to engage in favorable interactions. Further analysis of atomistic changes of both enzymes showed increased C-α atom deviations and an increase C-α atoms radius of gyration consistent with structural disorientations. These conformational changes possibly interfered with the enzymes' biological functions and hence their inhibition as experimentally reported. Additionally, in this domain, the therapeutic targeting of the ATP machinery of Mtb by Bedaquiline (BDQ) was explored towards unravelling the structures and atomistic perspectives that account for the ability of BDQ to selectively inhibits mycobacterial F1Fo-ATP synthase via its rotor c-ring. BDQ is shown to form strong interaction with Glu65B and Asp32B and, consequently, block these residues' role in proton binding and ion. BDQ binding was also revealed to impede the rotatory motion of the rotor c-ring by inducing a compact conformation on the ring with its bulky structure. Complementary binding of two molecules of BDQ to the rotor c-ring, proving that increasing the number of BDQ molecule enhances inhibitory potency. The last study in this research domain investigated the impact of triple mutations (L59V, E61D, and I66M) on the binding of BDQ to Mtb F1F0 ATP-synthase. The study showed that the mutations significantly impacted the binding affinity of BDQ, evidenced by a decrease in the estimated binding free energy (ΔG). Likewise, the structural integrity and conformational architecture of F1F0 ATP-synthase was distorted due to the mutation, which could have interfered with the binding of BDQ. The third domain of the research in this thesis investigated some small molecule inhibitors' inhibitory mechanism against some therapeutic targets in cancer, specifically PTPRZ and hTCRvi CD1d. Studies in the third domain of the research in the thesis began with the investigation of the investigation of the inhibitory mechanism of NAZ2329, an allosteric inhibitor of PTPRZ, by specifical investigating its binding effect on the atomic flexibility of the WPD-loop. Having been established as crucial determinant of the catalytic activity of PTPRZ an implicated protein in glioblastoma cells, its successfully therapeutic modulation could present a viable treatment option in glioblastoma. Structural insights from an MD simulation revealed that NAZ2329 binding induces an open conformation of the WPD-loop which subsequently prevents the participation of the catalytic aspartate of PTPRZ from participating in catalysis hence inhibiting the activity of PTPRZ. A pharmacophore was also created based of high energy contributing residues which highlighted essential moieties of NAZ2329 and could be used in screening compound libraries for potential inhibitors of PTPRZ. A second study in this domain sought to explore how structural modification could improve a therapeutic agent's potency from an atomistic perspective. This study was based on an earlier report in which the incorporation of a hydrocinnamoyl ester on C6’’ and C4-OH truncation of the sphingoid base of KRN7000 generated a novel compound AH10-7 high therapeutic potency and selectivity in human TCR-CD1d and subsequently results in the activation of invariant natural killer T cells (iNKT). The hydrocinnamoyl ester moiety was shown to engage in high-affinity interactions, possibly accounting for the selectivity and higher potency of AH10-7. Molecular and structural perspectives provided could aid in the design of novel α-GalCer derivatives for cancer immunotherapeutics. Chapter 3 provides theoretical insights into the various molecular modeling tools and techniques employed to investigate the various conformational changes, structural conformations, and the associated mechanism of inhibitions of the studied inhibitors towards viral, tuberculosis, and cancer therapy. Chapter 4 provided sufficient details on druggability and drug-likeness principles and their recent advancements in the drug discovery field. The study also presents the different computational tools and their reliability of predictive analysis in the drug discovery domain. It thus provides a comprehensive guide for computational-oriented drug discovery research. Chapter 5 provides an understanding of the binding mechanism of Remdesivir, providing structural and conformational implications on SARS-CoV-2 RdRp upon its binding and identifying its crucial pharmacophoric moieties. Chapter 6 explains the mechanism of inhibition of a novel benzothiophene derivative, revealing its distortion of the native extensively networked and compact residue profile. Chapter 7 unravels molecular and structural bases behind this dual inhibitory potential of the novel inhibitor IMP-1088 toward common cold therapy using augmentative computational and cheminformatics methods. The study also highlights the pharmacological propensities of IMP- 1088. Chapter 8 unravels the molecular mechanisms and structural dynamics of the dual inhibitory activity of PAS-M towards DHFR and FDTS. Chapter 9 reports the structural dynamics and atomistic perspectives that account for the reported ability of BDQ to halt the ion shuttling ability of mycobacterial c-ring. Chapter 10 presents the structural dynamics and conformational changes that occur on Mtb F1F0 ATP-synthase binding as a result of the triple mutations using molecular dynamics simulations, free energy binding, and residue interaction network (RIN) analyses. Chapter 11 explored the impact of NAZ2329, a recently identified allosteric inhibitor of Protein Tyrosine Phosphatase Receptor Zeta (PTPRZ), on the atomic flexibility of the WPD-loop, an essential loop in the inhibition of PTPRZ. The study also presents the drug-likeness of NAZ2329 using in silico techniques and its general inhibitory mechanism. Chapter 12 provides atomistic insights into the structural dynamics and selective mechanisms of AH10-7 for human TCR-CD1d towards activating iNKT cells. The studies in this thesis collectively present a thorough and comprehensive in silico perspective that characterizes the pharmacological inhibition of some known therapeutic targets in viral infections, tuberculosis, and cancer. The augmentative integration of computational methods to provide structural insights could help design highly selective inhibitors of these therapeutic targets. Therefore, the findings presented are fundamental to the design and development of next generation lead compounds with improved therapeutic activities and minimal toxicities

Architectural notes: a framework for distributed systems development

This thesis develops a framework of methods and techniques for distributed systems development. This framework consists of two related domains in which design concepts for distributed systems are defined: the entity domain and the behaviour domain. In the entity domain we consider structures of functional entities and their interconnection, while in the behaviour domain we consider behaviour definition and structuring. An interaction in which we abstract from the particular responsibilities of the participating functional entities is considered as an action. Behaviours consist of actions, interactions and their relationships. Relationships between actions and interactions are defined in terms of causality relations. In each causality relation the conditions and constraints for an action or interaction to occur are defined. Two important behaviour structuring techniques have been identified from the possible ways causality relations can be distributed: causality-oriented behaviour composition and constraint-oriented behaviour composition. Causality-oriented behaviour composition consists of placing some conditions of an action and the action itself in different sub-behaviours. Constraint-oriented behaviour composition consists of placing parts of the conditions and constraints of an action in different sub-behaviours, such that this action is shared by these sub-behaviours. This thesis identifies milestones in the design process of distributed systems, as well as the design steps to move from one milestone to another. These design steps are characterized using the concepts of the entity and the behaviour domain. We identified two crucial design operations of the behaviour domain that support these design steps: behaviour refinement and action refinement. Behaviour refinement consists of introducing (internal) structure in the causality relations of reference actions of an abstract behaviour, but preserving their causality and exclusion relationships and their attribute values. Action refinement consists of replacing abstract actions by activities, such that the completion of these activities correspond to the occurrence of the abstract actions. One important characteristic of action refinement is the possibility of distributing attribute values of the abstract actions over actions of the activities that replace them in the concrete behaviours. The area of research, scope and objectives of this thesis are discussed in Chapter 1. The concept of design culture and its elements is introduced in this chapter in order to provide an overview of the important aspects of the design process. Entity domain, behaviour domain, and design milestones are introduced and discussed in Chapter 2. This chapter also discusses the global objectives of design steps, and the abstraction obtained by considering interactions between cooperating functional entities as actions of the interaction system between these entities. Action, action attributes, causality and exclusion are discussed in Chapter 3. This chapter shows how a behaviour can be defined in terms of the causality relations of its actions in a monolithic form. Causality-oriented behaviour composition is discussed in Chapter 4. Entries and exits of a behaviour are the mechanisms that make it possible to assign parts of a condition of an action and the action itself to different sub-behaviours. Constraint-oriented behaviour composition is discussed in Chapter 5. Decomposition possibilities of monolithic behaviours are systematically studied in this chapter. Behaviour refinement is discussed in Chapter 6. This chapter defines a method to obtain an abstraction of a concrete behaviour. This method can be used to check whether the concrete behaviour corresponds to a certain abstract behaviour. Action refinement is discussed in Chapter 7. This chapter identifies some activity forms, and define the rules for considering these activities as implementations of an abstract action. These rules are used in a method to derive an abstraction of a concrete behaviour in which the abstract actions are implemented as activities. This method can be used to check whether the concrete behaviour corresponds to a certain abstract behaviour. Chapter 8 discusses a design example that is meant to illustrate the use of our design concepts. The example is an interaction server, which is a component that supports the interaction between multiple functional entities. Chapter 9 draws some conclusions and revisits the design milestones of Chapter 2, showing alternatives for the design trajectory which have been created with the use of actions and interactions in a single framework

Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations

Tracing the transmission of Scandinavian literature to the UK: 1917-2017

The interest in understanding how books move from a Scandinavian source culture to the British target culture has never been greater. This thesis analyses this buoyant demand by tracing the transmission of Scandinavian literature to Britain and its relationship with the British literary market over the past century. Through a series of case studies, the thesis examines what influences the likelihood of transmission and successful reception in Britain; the position of Scandinavian books in the British literary polysystem; how the transmission of Scandinavian books to Britain differs from the transmission to other polysystems; and how the publication practices of translated books have evolved. This approach is supported by an interdisciplinary framework encompassing translation, literary and sociocultural theories: key theoretical strands utilised are Holmes’ theory of function-oriented Descriptive Translation Studies, Even-Zohar’s polysystem theory, and Heilbron’s sociology of translation. In addition, elements of book history and patronage theory are also applied. The thesis comprises five case studies, spanning the years 1917-2017, of which one is Danish (Peter Høeg’s Miss Smilla’s Feeling for Snow), two are Norwegian (Knut Hamsun’s Growth of the Soil and Agnar Mykle’s four Ash Burlefoot novels), and two are Swedish (Maj Sjöwall and Per Wahlöö’s Martin Beck decalogy, and Stieg Larsson’s Millennium series, now continued by David Lagercrantz). Each of these case studies draws upon a wide range of sources, including newspapers, periodicals, archival materials, interview transcripts, industry statistics, and a range of scholarship, in order to provide comprehensive and contextualised insight into the transmission and reception trajectory of its respective subject, exploring the sociological and literary background to both production and reception. The increasing commercialisation of publishing, and more specifically of translated Scandinavian literature, is explored alongside literary and social changes, with emphasis on the tendency for transmission to be most likely at moments of paradigmatic shift in British society. This is especially reflected in the emergence of genre fiction and hybrid forms of writing during the period in question. Taken in combination, the case studies generate significant and original findings by identifying and analysing overarching trends that cannot be established through examining just one case subject or one source language. They both provide an historical account of Scandinavian literary transmission to Britain during the twentieth and early-twenty- first centuries, and they identify and analyse the significant factors involved in that process. The research offers an enhanced understanding of the contemporary situation of the publication of Scandinavian books in Britain

Verification of LOTOS Specifications Using Term Rewriting Techniques

Recently the use of formal methods in describing and analysing the behaviour of (computer) systems has become more common. This has resulted in the proliferation of a wide variety of different specification formalisms, together with analytical techniques and methodologies for specification development. The particular specification formalism adopted for this study is LOTOS, an ISO standard formal description technique. Although there are many works dealing with how to write LOTOS specifications and how to develop a LOTOS specification from the initial abstract requirements specification to concrete implementation, relatively few works are concerned with the problems of expressing and proving the correctness of LOTOS specifications, i.e. verification. The main objective of this thesis is to address this shortfall by investigating the meaning of verification as it relates to concurrent systems in general, and in particular to those systems described using LOTUS. Further goals are to automate the verification process using equational reasoning and term rewriting, and also to attempt to make the results of this work, both theoretical and practical, as accessible to LOTOS practitioners as possible. After introducing the LOTUS language and related formalisms, the thesis continues with a survey of approaches to verification of concurrent systems with a view to identifying those approaches suitable for use in verification of properties of systems specified using LOTOS. Both general methodology and specific implementation techniques are considered. As a result of this survey, two useful approaches are identified. Both are based on the technique of expressing the correctness of a LOTUS specification by comparison with another, typically more abstract, specification. The second approach, covered later in the thesis, uses logic for the more abstract specification. The main part of the thesis is concerned with the first approach, in which both specifications are described in LOTUS, and the comparison is expressed by a behavioural equivalence or preorder relation. This approach is further explored by means of proofs based on the paradigm of equational reasoning, implemented by term rewriting. Initially, only Basic LOTUS (i.e. the process algebra) is considered. A complete (i.e. confluent and terminating) rule set for weak bisimulation congruence over a subset of Basic LOTOS is developed using RRL (Rewrite Rule Laboratory). Although fully automatic, this proof technique is found to be insufficient for anything other than finite toy examples. In order to give more power, the rule set is supplemented by an incomplete set of rules expressing the expansion law. The incompleteness of the rule set necessitates the use of a strategy in applying the rules, as indiscriminate application of the rules may lead to non-termination of the rewriting. A case study illustrates the use of these rules, and also the effect of different interpretations of the verification requirement on the outcome of the proof. This proof technique, as a result of the deficiencies of the tool on which it is based, has two major failings: an inability to handle recursion, and no opportunity for user control in the proof. Moving to a different tool, PAM (Process Algebra Manipulator), allows correction of these faults, but at the cost of automation. The new implementation acts merely as computerised pencil and paper, although tactics can be defined which allow some degree of automation. Equations may be applied in either direction, therefore completion is no longer as important. (Note that the tactic language could be used to describe a a complete set of rules which would give an automatic proof technique, therefore some effort towards completion is still desirable. However, since LOTOS weak bisimulation congruence is undecidable, there can never be a complete rule set for deciding equivalence of terms from the full LOTUS language.) The composition of the rule set is re-considered, with a. view to using alternative axiomatisations of weak bisimulation congruence: two main axiomatisations are described and their relative merits compared. The axiomatisation of other LOTUS relations is also considered. In particular, we consider the pitfalls of axiomatising the cred preorder relation. In order to demonstrate the use of the PAM proof system developed, the case study, modified to use recursion, is re-examined. Four other examples taken from the literature, one substantial, the others fairly small, are also investigated to further demonstrate the applicability of the PAM proof system to a variety of examples. The above approach considers Basic LOTUS only; to be more generally applicable the verification of properties of full LOTOS specifications (i.e. including abstract data types) must also be studied. Methods for proving the equivalence of full LOTUS specifications are examined, including a modification of the technique used successfully above. The application of this technique is illustrated via proofs of the equivalence of three variants of the well-known stack example

Evidence for improving services for glaucoma in Nigeria: Epidemiology, ophthalmologists' practice pattern, patients' access to care and community experiences of glaucoma.

Glaucoma is the second leading cause of blindness worldwide. Africa region has the highest burden of glaucoma and glaucoma blindness.When diagnosed early and appropriate treatment sustained, blindness from glaucoma is avoidable. The Nigeria national blindness and visual impairment survey (NBS), with >13,500 people aged≥ 40 years examined, estimated the prevalence of blindness as 4.2% (95%CI 3.8-4.6%).16.7% was due to glaucoma, the leading cause of irreversible blindness and functional low vision. There are insufficient population-based glaucoma studies in Africa;!and the NBS provided the largest dataset in Africa from which data on glaucoma could be derived. In this study, analysis of the NBS data using established criteria from the International Society of Geographical and Epidemiological Ophthalmology showed high prevalence of glaucoma (5.02%; 95%CI 4.60-5.47%): undiagnosed in 94%; and open-angle glaucoma (OAG) in 86%. One -in -five persons with glaucoma were blind. Increasing age and higher intraocular pressure were independent risk factors for OAG; and some ethnic groups were more at risk. Glaucoma blindness was associated with socioeconomic deprivation, reflecting poor access to care. These findings underscored the high level of need for optimal glaucoma services. Information about glaucoma management obtained from 153 practising Ophthalmologists in Nigeria highlighted patient-related challenges of late presentation with advanced disease and poor compliance to treatment; and additional constraints due to inadequate access to equipment for diagnosis and treatment. In the qualitative study, we sought to understand access to glaucoma care and determine why people with glaucoma are presenting late for treatment. We found barriers of access to care which could be explained as evidence of structural inequalities associated with coping mechanisms and distinct social suffering. This study provided data required to develop evidence-based strategy for control of glaucoma blindness by improving glaucoma services in Nigeria. These data could also have implications to other Sub Saharan African countries with similar socioeconomic and ecological characteristics

Microfluidics for Biosensing

There are 12 papers published with 8 research articles, 3 review articles and 1 perspective. The topics cover: Biomedical microfluidics Lab-on-a-chip Miniaturized systems for chemistry and life science (MicroTAS) Biosensor development and characteristics Imaging and other detection technologies Imaging and signal processing Point-of-care testing microdevices Food and water quality testing and control We hope this collection could promote the development of microfluidics and point-of-care testing (POCT) devices for biosensing

Safety and Reliability - Safe Societies in a Changing World

The contributions cover a wide range of methodologies and application areas for safety and reliability that contribute to safe societies in a changing world. These methodologies and applications include: - foundations of risk and reliability assessment and management - mathematical methods in reliability and safety - risk assessment - risk management - system reliability - uncertainty analysis - digitalization and big data - prognostics and system health management - occupational safety - accident and incident modeling - maintenance modeling and applications - simulation for safety and reliability analysis - dynamic risk and barrier management - organizational factors and safety culture - human factors and human reliability - resilience engineering - structural reliability - natural hazards - security - economic analysis in risk managemen

Development of SLA 3D printed drug eluting medical implants for local cancer treatment

The current dogma of drug formulation technology places heavy focus upon the use of systemic oral or intravenous routes, for the delivery of a medicine to a target tissue. An inherent problem with this approach is the requirement of a high dosing regimen to ensure that the drug reaches the site of interest for optimal therapeutic effect. However, this can lead to the prevalence of ‘off-target’ effects and poor compliance. In the case of cancer, the ‘off-target’ effects of cytotoxic chemotherapeutics can cause greater harm than benefit to the patient. The aim of this project is to develop a medical implant that obviates the requirement of systemic dosing by providing a method of local drug release to the target area. Through utilisation of SLA 3D printing, we aim to develop and produce a drug eluting device that provides unidirectional release of patient-specific payloads at pre-determined pharmacokinetic rates. However, before a specific focus could be placed on cancer, three major problems associated with SLA 3D printing pharmaceutics had to be solved. Firstly, SLA 3D printed materials have unsuitable physical properties for medical device applications. Secondly, photopolymer systems based on (meth)acrylate photopolymer systems are associate with toxicity and hence have limited use as pharmaceutics. Finally, commercial SLA 3D printers do not support the use of custom photopolymer systems. Solving each of these problems would provide solid groundwork for the development of SLA 3D printed drug eluting implants for local chemotherapy. To solve the issue of poor mechanical properties, a range of current and novel photopolymers were synthesised, characterised and compared against one another and reference materials. To solve the issue of material toxicity, different post-processing procedures were explored and utilised in attempt to render SLA 3D printed materials as biocompatible. Finally, an RT-FTIR spectroscopy tool was developed to bridge the gap between unprintable and printable photopolymer systems. Furthermore, extensive drug release studies were conducted with aim to characterise effect of different SLA 3D printed materials on drug release kinetics