4,175 research outputs found

    HIV and AIDS in Greater Manchester: service delivery in times of devolution, neoliberalism and austerity

    Get PDF
    This research examines the impact of devolution, neoliberalism and austerity on the governance and delivery of specialist HIV and AIDS physical and mental health services for service users across the Manchester City Region. This research further documents the decline of specialist HIV and AIDS healthcare, including mental health services, over the last decade and details the extent of these changes on people living with HIV and AIDS across the Manchester City Region. Focusing on the interplay of neoliberal policy interventions with the structural changes implied in devolution, the research locates the participants' accounts within the broader analysis of cultural, political and economic developments in health policy and (urban) governance. This thesis draws on a queer-feminist methodology and a series of semi-structured interviews with service users of HIV and AIDS healthcare provisions; organisations specialising in HIV and AIDS support, advice and advocacy services to improve health outcomes; healthcare staff specialising in HIV and AIDS healthcare and those who advocate for improved treatments; academics who work in the field of HIV studies; and activists who are campaigning for improved HIV and AIDS services. The interview data was analysed to show how funding changes have affected the delivery of HIV and AIDS healthcare services. Secondary data sources, such as public health data, were also utilised to address gaps within the interview data. The interview data shows that the shift to cheaper generalist services results in poorer service provision because healthcare staff may not understand the full range of needs of service users with HIV and AIDS. Moreover, the study participants pointed to the persistence of discrimination in healthcare settings, leading to poorer mental health. As a result, service users may stop taking their antiretroviral treatments. Historically, HIV has been heavily stigmatised, and this is a theme which arose in the data. This study focuses on specific campaigns, such as “U=U” and “You Can’t Pass It On,” which attempt to combat HIV-associated stigma and discrimination by creating awareness. Still, the efforts of these campaigns have only tended to reach those who know about HIV. In response, there has been some work in Manchester to educate healthcare professionals, but this is limited and still in its infancy. This study further argues that there is an urgent need for increased investment in specialist HIV and AIDS healthcare services. There needs to be a refocus on providing services across the Manchester City Region. Furthermore, the research data analysis suggests that even more funding may be required to achieve the goal of advanced specialist training among health professionals to secure adequate healthcare provisions for people living with HIV and AIDS within the Greater Manchester City Region

    Distributed Ledger Technology (DLT) Applications in Payment, Clearing, and Settlement Systems:A Study of Blockchain-Based Payment Barriers and Potential Solutions, and DLT Application in Central Bank Payment System Functions

    Get PDF
    Payment, clearing, and settlement systems are essential components of the financial markets and exert considerable influence on the overall economy. While there have been considerable technological advancements in payment systems, the conventional systems still depend on centralized architecture, with inherent limitations and risks. The emergence of Distributed ledger technology (DLT) is being regarded as a potential solution to transform payment and settlement processes and address certain challenges posed by the centralized architecture of traditional payment systems (Bank for International Settlements, 2017). While proof-of-concept projects have demonstrated the technical feasibility of DLT, significant barriers still hinder its adoption and implementation. The overarching objective of this thesis is to contribute to the developing area of DLT application in payment, clearing and settlement systems, which is still in its initial stages of applications development and lacks a substantial body of scholarly literature and empirical research. This is achieved by identifying the socio-technical barriers to adoption and diffusion of blockchain-based payment systems and the solutions proposed to address them. Furthermore, the thesis examines and classifies various applications of DLT in central bank payment system functions, offering valuable insights into the motivations, DLT platforms used, and consensus algorithms for applicable use cases. To achieve these objectives, the methodology employed involved a systematic literature review (SLR) of academic literature on blockchain-based payment systems. Furthermore, we utilized a thematic analysis approach to examine data collected from various sources regarding the use of DLT applications in central bank payment system functions, such as central bank white papers, industry reports, and policy documents. The study's findings on blockchain-based payment systems barriers and proposed solutions; challenge the prevailing emphasis on technological and regulatory barriers in the literature and industry discourse regarding the adoption and implementation of blockchain-based payment systems. It highlights the importance of considering the broader socio-technical context and identifying barriers across all five dimensions of the social technical framework, including technological, infrastructural, user practices/market, regulatory, and cultural dimensions. Furthermore, the research identified seven DLT applications in central bank payment system functions. These are grouped into three overarching themes: central banks' operational responsibilities in payment and settlement systems, issuance of central bank digital money, and regulatory oversight/supervisory functions, along with other ancillary functions. Each of these applications has unique motivations or value proposition, which is the underlying reason for utilizing in that particular use case

    Context-Dependent Acquisition of Antimicrobial Resistance Mechanisms

    Get PDF
    Natural transformation is a process whereby bacteria actively take up free DNA from the environment while in a physiological state termed competence. Uptaken DNA is then recombined into the recipient’s genome or reconverted into extra-chromosomal genetic elements. The inducing stimuli for competence vary widely between transformable species and competence induction is affected by a host of abiotic factors found in bacterial environments. Natural transformation is recognised to be responsible for the dissemination of antimicrobial resistance genes both within and between species, contributing to the global antimicrobial resistance crisis threatening modern medicine. Despite being the first mechanism of horizontal gene transfer discovered, the evolutionary benefits of natural transformation are still under debate. This thesis is comprised of four standalone research chapters which aimed 1) to determine if chemotherapeutic compounds affect the transformation frequencies of transformable bacteria. This provides important information which can have implications on the contraction of a life-threatening infection in cancer patients. 2) to determine if other environmentally relevant bacteria affect the transformation frequencies of transformable bacteria. Understanding the contexts under which bacteria transform in their natural environments can help us to predict the spread of antimicrobial resistance mechanisms via natural transformation. 3) to produce a resource of genomic information for the scientific community, allowing researchers to improve our understanding of the Acinetobacter genus. And 4) to determine if environmentally relevant bacteria affect the transformation frequencies of transformable bacteria to find evidence for the sex hypothesis for natural transformation. This was performed by using biotic interactions as a selection pressure and DNA from a range of related species as a substrate for transformation. Together, these chapters provide information about the contexts under which transformation is both regulated and selected for in realistic environmental contexts. Enhancing our understanding of how and when bacteria naturally transform, in both natural and clinical environments, can help us to monitor and establish preventative measures to limit the spread of antimicrobial resistance genes between bacteria

    Evidence of interspecific plasmid uptake by pathogenic strains of Klebsiella isolated from microplastic pollution on public beaches

    Get PDF
    Microplastic beads are becoming a common feature on beaches, and there is increasing evidence that such microplastics can become colonised by potential human pathogens. However, whether the concentrations and pathogenicity of these pathogens pose a public health risk are still unclear. Therefore, the aim of this study was to determine realistic environmental concentrations of potential pathogens colonising microplastic beads, and quantify the expression of virulence and antimicrobial resistance genes (ARGs). Microplastic beads were collected from beaches and a culture-dependent approach was used to determine the concentrations of seven target bacteria (Campylobacter spp.; E. coli; intestinal enterococci; Klebsiella spp.; Pseudomonas aeruginosa; Salmonella spp.; Vibrio spp.). All seven target bacteria were detected without the need for a pre-enrichment step; urban sites had higher bacterial concentrations, whilst polymer type had no influence on bacterial concentrations. Klebsiella was the most abundant target bacteria and possessed virulence and ARGs, some of which were present on plasmids from other species, and showed pathogenicity in a Galleria melonella infection model. Our findings demonstrate how pathogen colonised microplastic beads can pose a heightened public health risk at the beach, and highlights the urgency for improved monitoring and enforcement of regulations on the release of microplastics into the environment

    Satellite remote sensing of surface winds, waves, and currents: Where are we now?

    Get PDF
    This review paper reports on the state-of-the-art concerning observations of surface winds, waves, and currents from space and their use for scientific research and subsequent applications. The development of observations of sea state parameters from space dates back to the 1970s, with a significant increase in the number and diversity of space missions since the 1990s. Sensors used to monitor the sea-state parameters from space are mainly based on microwave techniques. They are either specifically designed to monitor surface parameters or are used for their abilities to provide opportunistic measurements complementary to their primary purpose. The principles on which is based on the estimation of the sea surface parameters are first described, including the performance and limitations of each method. Numerous examples and references on the use of these observations for scientific and operational applications are then given. The richness and diversity of these applications are linked to the importance of knowledge of the sea state in many fields. Firstly, surface wind, waves, and currents are significant factors influencing exchanges at the air/sea interface, impacting oceanic and atmospheric boundary layers, contributing to sea level rise at the coasts, and interacting with the sea-ice formation or destruction in the polar zones. Secondly, ocean surface currents combined with wind- and wave- induced drift contribute to the transport of heat, salt, and pollutants. Waves and surface currents also impact sediment transport and erosion in coastal areas. For operational applications, observations of surface parameters are necessary on the one hand to constrain the numerical solutions of predictive models (numerical wave, oceanic, or atmospheric models), and on the other hand to validate their results. In turn, these predictive models are used to guarantee safe, efficient, and successful offshore operations, including the commercial shipping and energy sector, as well as tourism and coastal activities. Long-time series of global sea-state observations are also becoming increasingly important to analyze the impact of climate change on our environment. All these aspects are recalled in the article, relating to both historical and contemporary activities in these fields

    Investigating the early interaction between Mycobacterium avium ssp paratuberculosis and the host using a bovine enteroid system

    Get PDF
    Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic granulomatous enteritis of ruminant’s prevalent world-wide. Infection of calves occurs through the faecal oral route, typically in animals <6 months old. Animals are asymptomatic for 2-5 years before clinical signs begin to show, which typically present as emaciation and chronic diarrhoea. In the subclinical phase, animals will have decreased milk yield, increased susceptibility to other diseases and decreased feed conversion. This has a severe impact on the farming economy and animal welfare, as affected animals are often prematurely culled. Infected subclinical animals are extremely difficult to identify but can still act as a source of transmission for the rest of the herd by shedding MAP in their faeces. There is no treatment for JD, and the current diagnostic tests are ineffective. By investigating the initial interaction between MAP and the host at the intestinal lining, a greater understanding of MAP pathogenesis can be gained and better diagnostic and therapeutic targets can be identified. In this work, proteins expressed on the surface of MAP were assessed for their ability to aid attachment, invasion and intracellular survival in epithelial and phagocytic cells when expressed on the membrane of a non-invasive E. coli host strain. The proteins investigated were encoded by mammalian cell entry (mce) genes, mce1A, mce1D, mce3C and mce4A, which have been implicated in attachment and invasion of epithelial cells by other mycobacteria. Interestingly, E. coli expressing Mce1A had enhanced uptake by phagocytic cells and E. coli expressing Mce1D had enhanced attachment and invasion of epithelial cells, but neither protein conferred this phenotype in both eukaryotic cell types investigated. To identify key intestinal cell types involved in MAP pathogenesis, bovine intestinal organoids (enteroids) were assessed for their ability to model a MAP infection in a physiologically representative system. Baso-out 3D enteroids, apical-out 3D enteroids and 2D monolayers were created, and the cell types present were compared to bovine intestinal tissue samples using RT-PCR and immunofluorescence microscopy. The models contained the mature epithelial cell types of the intestine including goblet cells, enteroendocrine cells, Paneth cells and enterocytes. 3D baso-out enteroids and 2D monolayers also contained proliferative cells, but the 3D apical-out enteroids did not and so could not be maintained past 2 weeks of culture. The models were infected with two strains of MAP over the course of 72 hours, the reference strain K10, and a recent clinical isolate C49. MAP C49 was shown to be present in all three intestinal models in consistently higher numbers than MAP K10, quantified using qPCR of the genomic DNA. This indicates that MAP C49 was better able to infect these models than K10, which may suggest a loss of virulence in MAP K10. Overall, the data presented has increased our understanding of MAP pathogenesis by emphasising the need for multicellular models which accurately represent the pathogen target cell type/s in vivo and the confirmation of the role of two hypothetical MAP proteins in cellular interactions

    Abstract Book of the II Congress of the Latin American Society for Vector Ecology

    Get PDF
    Recopilación de los resúmenes de las conferencias, simposios, paneles de discusión y "turbo talks" ofrecidos en el II Congreso de la Sociedad Latinoamericana de Ecología de Vectores (LA SOVE), realizado entre el 29 de octubre y el 3 de noviembre de 2022 en la ciudad de La Plata (Buenos Aires, Argentina).Sociedad Latinoamericana de Ecología de Vectores (LA SOVE

    Design and Real-World Evaluation of Dependable Wireless Cyber-Physical Systems

    Get PDF
    The ongoing effort for an efficient, sustainable, and automated interaction between humans, machines, and our environment will make cyber-physical systems (CPS) an integral part of the industry and our daily lives. At their core, CPS integrate computing elements, communication networks, and physical processes that are monitored and controlled through sensors and actuators. New and innovative applications become possible by extending or replacing static and expensive cable-based communication infrastructures with wireless technology. The flexibility of wireless CPS is a key enabler for many envisioned scenarios, such as intelligent factories, smart farming, personalized healthcare systems, autonomous search and rescue, and smart cities. High dependability, efficiency, and adaptivity requirements complement the demand for wireless and low-cost solutions in such applications. For instance, industrial and medical systems should work reliably and predictably with performance guarantees, even if parts of the system fail. Because emerging CPS will feature mobile and battery-driven devices that can execute various tasks, the systems must also quickly adapt to frequently changing conditions. Moreover, as applications become ever more sophisticated, featuring compact embedded devices that are deployed densely and at scale, efficient designs are indispensable to achieve desired operational lifetimes and satisfy high bandwidth demands. Meeting these partly conflicting requirements, however, is challenging due to imperfections of wireless communication and resource constraints along several dimensions, for example, computing, memory, and power constraints of the devices. More precisely, frequent and correlated message losses paired with very limited bandwidth and varying delays for the message exchange significantly complicate the control design. In addition, since communication ranges are limited, messages must be relayed over multiple hops to cover larger distances, such as an entire factory. Although the resulting mesh networks are more robust against interference, efficient communication is a major challenge as wireless imperfections get amplified, and significant coordination effort is needed, especially if the networks are dynamic. CPS combine various research disciplines, which are often investigated in isolation, ignoring their complex interaction. However, to address this interaction and build trust in the proposed solutions, evaluating CPS using real physical systems and wireless networks paired with formal guarantees of a system’s end-to-end behavior is necessary. Existing works that take this step can only satisfy a few of the abovementioned requirements. Most notably, multi-hop communication has only been used to control slow physical processes while providing no guarantees. One of the reasons is that the current communication protocols are not suited for dynamic multi-hop networks. This thesis closes the gap between existing works and the diverse needs of emerging wireless CPS. The contributions address different research directions and are split into two parts. In the first part, we specifically address the shortcomings of existing communication protocols and make the following contributions to provide a solid networking foundation: • We present Mixer, a communication primitive for the reliable many-to-all message exchange in dynamic wireless multi-hop networks. Mixer runs on resource-constrained low-power embedded devices and combines synchronous transmissions and network coding for a highly scalable and topology-agnostic message exchange. As a result, it supports mobile nodes and can serve any possible traffic patterns, for example, to efficiently realize distributed control, as required by emerging CPS applications. • We present Butler, a lightweight and distributed synchronization mechanism with formally guaranteed correctness properties to improve the dependability of synchronous transmissions-based protocols. These protocols require precise time synchronization provided by a specific node. Upon failure of this node, the entire network cannot communicate. Butler removes this single point of failure by quickly synchronizing all nodes in the network without affecting the protocols’ performance. In the second part, we focus on the challenges of integrating communication and various control concepts using classical time-triggered and modern event-based approaches. Based on the design, implementation, and evaluation of the proposed solutions using real systems and networks, we make the following contributions, which in many ways push the boundaries of previous approaches: • We are the first to demonstrate and evaluate fast feedback control over low-power wireless multi-hop networks. Essential for this achievement is a novel co-design and integration of communication and control. Our wireless embedded platform tames the imperfections impairing control, for example, message loss and varying delays, and considers the resulting key properties in the control design. Furthermore, the careful orchestration of control and communication tasks enables real-time operation and makes our system amenable to an end-to-end analysis. Due to this, we can provably guarantee closed-loop stability for physical processes with linear time-invariant dynamics. • We propose control-guided communication, a novel co-design for distributed self-triggered control over wireless multi-hop networks. Self-triggered control can save energy by transmitting data only when needed. However, there are no solutions that bring those savings to multi-hop networks and that can reallocate freed-up resources, for example, to other agents. Our control system informs the communication system of its transmission demands ahead of time so that communication resources can be allocated accordingly. Thus, we can transfer the energy savings from the control to the communication side and achieve an end-to-end benefit. • We present a novel co-design of distributed control and wireless communication that resolves overload situations in which the communication demand exceeds the available bandwidth. As systems scale up, featuring more agents and higher bandwidth demands, the available bandwidth will be quickly exceeded, resulting in overload. While event-triggered control and self-triggered control approaches reduce the communication demand on average, they cannot prevent that potentially all agents want to communicate simultaneously. We address this limitation by dynamically allocating the available bandwidth to the agents with the highest need. Thus, we can formally prove that our co-design guarantees closed-loop stability for physical systems with stochastic linear time-invariant dynamics.:Abstract Acknowledgements List of Abbreviations List of Figures List of Tables 1 Introduction 1.1 Motivation 1.2 Application Requirements 1.3 Challenges 1.4 State of the Art 1.5 Contributions and Road Map 2 Mixer: Efficient Many-to-All Broadcast in Dynamic Wireless Mesh Networks 2.1 Introduction 2.2 Overview 2.3 Design 2.4 Implementation 2.5 Evaluation 2.6 Discussion 2.7 Related Work 3 Butler: Increasing the Availability of Low-Power Wireless Communication Protocols 3.1 Introduction 3.2 Motivation and Background 3.3 Design 3.4 Analysis 3.5 Implementation 3.6 Evaluation 3.7 Related Work 4 Feedback Control Goes Wireless: Guaranteed Stability over Low-Power Multi-Hop Networks 4.1 Introduction 4.2 Related Work 4.3 Problem Setting and Approach 4.4 Wireless Embedded System Design 4.5 Control Design and Analysis 4.6 Experimental Evaluation 4.A Control Details 5 Control-Guided Communication: Efficient Resource Arbitration and Allocation in Multi-Hop Wireless Control Systems 5.1 Introduction 5.2 Problem Setting 5.3 Co-Design Approach 5.4 Wireless Communication System Design 5.5 Self-Triggered Control Design 5.6 Experimental Evaluation 6 Scaling Beyond Bandwidth Limitations: Wireless Control With Stability Guarantees Under Overload 6.1 Introduction 6.2 Problem and Related Work 6.3 Overview of Co-Design Approach 6.4 Predictive Triggering and Control System 6.5 Adaptive Communication System 6.6 Integration and Stability Analysis 6.7 Testbed Experiments 6.A Proof of Theorem 4 6.B Usage of the Network Bandwidth for Control 7 Conclusion and Outlook 7.1 Contributions 7.2 Future Directions Bibliography List of Publication

    Advances and Applications of DSmT for Information Fusion. Collected Works, Volume 5

    Get PDF
    This fifth volume on Advances and Applications of DSmT for Information Fusion collects theoretical and applied contributions of researchers working in different fields of applications and in mathematics, and is available in open-access. The collected contributions of this volume have either been published or presented after disseminating the fourth volume in 2015 in international conferences, seminars, workshops and journals, or they are new. The contributions of each part of this volume are chronologically ordered. First Part of this book presents some theoretical advances on DSmT, dealing mainly with modified Proportional Conflict Redistribution Rules (PCR) of combination with degree of intersection, coarsening techniques, interval calculus for PCR thanks to set inversion via interval analysis (SIVIA), rough set classifiers, canonical decomposition of dichotomous belief functions, fast PCR fusion, fast inter-criteria analysis with PCR, and improved PCR5 and PCR6 rules preserving the (quasi-)neutrality of (quasi-)vacuous belief assignment in the fusion of sources of evidence with their Matlab codes. Because more applications of DSmT have emerged in the past years since the apparition of the fourth book of DSmT in 2015, the second part of this volume is about selected applications of DSmT mainly in building change detection, object recognition, quality of data association in tracking, perception in robotics, risk assessment for torrent protection and multi-criteria decision-making, multi-modal image fusion, coarsening techniques, recommender system, levee characterization and assessment, human heading perception, trust assessment, robotics, biometrics, failure detection, GPS systems, inter-criteria analysis, group decision, human activity recognition, storm prediction, data association for autonomous vehicles, identification of maritime vessels, fusion of support vector machines (SVM), Silx-Furtif RUST code library for information fusion including PCR rules, and network for ship classification. Finally, the third part presents interesting contributions related to belief functions in general published or presented along the years since 2015. These contributions are related with decision-making under uncertainty, belief approximations, probability transformations, new distances between belief functions, non-classical multi-criteria decision-making problems with belief functions, generalization of Bayes theorem, image processing, data association, entropy and cross-entropy measures, fuzzy evidence numbers, negator of belief mass, human activity recognition, information fusion for breast cancer therapy, imbalanced data classification, and hybrid techniques mixing deep learning with belief functions as well

    Immune Mechanisms of Microbial Cancer Therapy

    Full text link
    Neutrophils are responsible for protection from microbial infections. But they can also infiltrate solid tumours, and their presence within tumours is linked with cancer growth and poorer prognosis. However, this view oversimplifies their relationship with tumours, as recent research suggests that neutrophils also have anti-tumour properties. In addition, neutrophils possess considerable functional plasticity, and physiological and pathological factors can alter their function. In this study, we examined how neutrophil plasticity could be exploited to shift the tumour immune microenvironment to favour the inhibition of cancer growth. We achieved this by injecting inactivated Staphylococcus aureus (S. aureus) bioparticles into tumours. As a result, the TME (TME) was altered by the rapid influx of activated neutrophils that had acquired a pathogen killing effector phenotype. When examined using two-photon microscopy, S. aureus bioparticle activated neutrophils within tumours had increased motility and interacted with tumour cells. Repeated administration of S. aureus bioparticle therapy maintained a neutrophil activating environment within tumours. This led to neutrophil-dependent inhibition of tumour growth, highlighting an important role for microbe activated neutrophils in achieving cancer control. S. aureus bioparticle treatment also enhanced CD8+ T cell responses within tumours and draining lymph nodes. Notably, mice treated with our microbial therapy were protected from cancer recurrence, which suggests that a long-lasting protective immune response was elicited by the treatment. In keeping with these results, we found that S. aureus bioparticle treatment had a synergistic tumour inhibiting effect when combined with systemic checkpoint inhibitor therapy. In conclusion, we demonstrated that neutrophils are critical for microbe based cancer immunotherapy. We leveraged neutrophil plasticity and their rapid tissue infiltration in response to S. aureus bioparticle induced inflammation to alter the TME and control tumour growth. This body of research supports a model for developing neutrophil based immunotherapy using microbial bioparticles and its application with existing clinical cancer therapies
    corecore