Organisational Legitimacy, Capacity and Capacity Development

The European Centre for Development Policy Management (ECDPM) has undertaken a study of capacity development, with a focus on organisational change and performance enhancement. Both individual organisations and networks of organisations have been studied with the aim of identifying important relationships among endogenous change factors (e.g. ownership, commitment and managerial style), key internal organisation variables (e.g. structures, procedures, staffing and management systems), performance and sustainability outcomes, and external environmental factors (e.g. policy frameworks, resource availability, politics, stakeholders, governance regimes, etc.).To date, the ECDPM study team has conducted 16 case studies (see Appendix). Among the findings that have emerged from several of the cases is the presence of an organisation's legitimacy as a factor contributing to successful capacity and performance. To delve in more detail into the concept of legitimacy, and to identify the implications for capacity building, ECDPM commissioned a working paper on the topic. This exploratory paper reviews the relevant literature and examines: differing definitions, types and sources of legitimacy; the links between legitimacy and organisational capacity, performance and sustainability; and management strategies for building and maintaining legitimacy. It discusses a selected set of the ECDPM cases in terms of the legitimacy concept

A Dynamic Approach to Linear Statistical Calibration with an Application in Microwave Radiometry

The problem of statistical calibration of a measuring instrument can be framed both in a statistical context as well as in an engineering context. In the first, the problem is dealt with by distinguishing between the 'classical' approach and the 'inverse' regression approach. Both of these models are static models and are used to estimate exact measurements from measurements that are affected by error. In the engineering context, the variables of interest are considered to be taken at the time at which you observe it. The Bayesian time series analysis method of Dynamic Linear Models (DLM) can be used to monitor the evolution of the measures, thus introducing an dynamic approach to statistical calibration. The research presented employs the use of Bayesian methodology to perform statistical calibration. The DLM's framework is used to capture the time-varying parameters that maybe changing or drifting over time. Two separate DLM based models are presented in this paper. A simulation study is conducted where the two models are compared to some well known 'static' calibration approaches in the literature from both the frequentist and Bayesian perspectives. The focus of the study is to understand how well the dynamic statistical calibration methods performs under various signal-to-noise ratios, r. The posterior distributions of the estimated calibration points as well as the 95% coverage intervals are compared by statistical summaries. These dynamic methods are applied to a microwave radiometry data set.Comment: 26 pages, 10 figure

Dynamic Bayesian Nonlinear Calibration

Statistical calibration where the curve is nonlinear is important in many areas, such as analytical chemistry and radiometry. Especially in radiometry, instrument characteristics change over time, thus calibration is a process that must be conducted as long as the instrument is in use. We propose a dynamic Bayesian method to perform calibration in the presence of a curvilinear relationship between the reference measurements and the response variable. The dynamic calibration approach adequately derives time dependent calibration distributions in the presence of drifting regression parameters. The method is applied to microwave radiometer data and simulated spectroscopy data based on work by Lundberg and de Mar\'{e} (1980)

Investigation Of The Neurological Manifestations Of Lyme Disease And The Impact Of Borrelia Burgdorferi On The Epigenetic Landscape Of Astrocytes

Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most commonly reported vector-borne disease in the United States – with 30,000 cases being reported to the CDC annually, though it is estimated that 300,000 individuals are infected each year in the U.S [1–4]. Due to the medical treatment of the disease, this equates to an estimated $712 million -$1.3 billion in medical costs each year [5]. Conclusively, due to the continued geographical spread and increasing incidence rate, Lyme disease is becoming a greater public health threat throughout the world. The symptoms of Lyme disease can range from erythema migrans to more systematic disorders such as arthritis and neurological complications, termed neuroborreliosis [6,7]. Manifestations of neuroborreliosis include radiculoneuritis, meningitis, and facial palsy [8–10]. Interestingly, B. burgdorferi does not produce any known toxins, and it is thought that the resulting host immune response leads to cellular and tissue damage associated with clinical symptoms. Although many individuals will be effectively treated through the administration of antibiotics, up to 20% of patients will experience on-going symptoms termed Post-treatment Lyme Disease Syndrome (PTLDS). PTLDS is marked by persistent musculoskeletal pain and neurological complications. Inflammatory states have been associated to these symptoms with the invasion of peripheral immune cells and an increase of inflammatory cytokines. Furthermore, the neurological complications of PTLDS has been associated with an increase in glial inflammation. It is well-documented that B. burgdorferi is capable of penetrating into the central nervous system (CNS); however, it is unknown how and where the bacterium does so. Additionally, the exact pathogenetic mechanisms of neuroborreliosis and PTLDS are poorly understood. The work within this dissertation aims to provide novel insight into these gaps in knowledge. This dissertation is laid out into three sections relating to understanding the pathogenesis of the neurological effects of Lyme disease. In the first study, we aimed to provide an explanation for the dissemination of B. burgdorferi and peripheral immune cells into the central nervous system. Clinical presentations of neuroborreliosis is associated with an increase of peripheral immune cells, inflammatory chemokines, and live B. burgdorferi in the cerebrospinal fluid (CSF). To this end, we sought to investigate a direct route from hematogenous dissemination into the CSF. The choroid plexus (CP) is a structure within the ventricles of the brain that is responsible for the production of CSF, the formation of the blood-CSF barrier, and regulation of the immune response. This barrier allows for the exchange of specific nutrients, waste, and peripheral immune cells between the blood stream and CSF. We hypothesize that during infection of the choroid plexus, Borrelia burgdorferi will induce an immune response conducive to the chemotaxis of immune cells and subsequently lead to a pro-inflammatory state within the CNS. To investigate this hypothesis, we cultured primary human choroid plexus epithelial cells and infected with the B. burgdorferi strain B31 MI-16 for 48 hours. RNA was isolated and used for RNA sequencing and RT-qPCR validation. Secreted proteins in the supernatant were analyzed via ELISA. Transcriptome analysis based on RNA sequencing determined a total of 160 upregulated genes and 98 downregulated genes. Pathway and biological process analysis determined a significant upregulation in immune and inflammatory genes specifically in chemokine and interferon related pathways. Further analysis revealed downregulation in genes related to cell to cell junctions including tight and adherens junctions. Protein analysis of secreted factors showed an increase in inflammatory chemokines, corresponding to our transcriptome analysis. These data further demonstrate the role of the CP in the modulation of the immune response in a disease state and give insight into the mechanisms by which Borrelia burgdorferi may disseminate into, and act upon, the CNS. Future experiments aim to detail the impact of B. burgdorferi on the blood-CSF-barrier (BCSFB) integrity and inflammatory response within animal models. The second and third study aim to elucidate the pathogenic mechanisms of neuroborreliosis and PTLDS, specifically the manifestations of a persistent inflammatory state. As B. burgdorferi has previously been shown to elicit an inflammatory response in astrocytes, and glial inflammation is associated with PTLDS, we sought to investigate the epigenetic modifications associated with the astrocytic response in order to determine a mechanistic explanation to these disorders. In the second study, we investigated the differential DNA methylation of astrocytes in response to three strains of B. burgdorferi – B31 MI-16, B31 e2, and 297 through the use of beadchip array. This study utilized primary human astrocytes in vitro. This study was met with a limiting factor in biological replicate variability that led to diminished results. Nevertheless, differential methylation within specific genes involving vesicle trafficking and cell communication were observed. This suggests that DNA methylation may be a mechanistic explanation for the changes in gene expression of astrocytes in response to B. burgdorferi. In the third study, we utilized the same astrocyte model of the second study to investigate the effects of B. burgdorferi on chromatin structure of astrocytes. We performed in vitro infection of astrocytes with the B31 MI-16 strain for 24, 48, 72, and 96 hours. Following infection, ATAC-seq was performed to interrogate the chromatin structure of astrocytes in response to B. burgdorferi. We observed a robust change in chromatin accessibility at 24-hours with 25,464 differential peaks. At 48, 72, and 96 hours, these peaks were reduced to 7,266, 3,376, and 3,015 respectively. Additionally, while many of the differential peaks were associated with open chromatin at 24, 48, and 72 hours, the 96-hour time point was marked by a dramatic decrease in chromatin accessibility. Many of the peaks within gene bodies at the first three time points were associated with changes in anatomical and morphological alterations, while the 96-hour time point was highlighted by metabolic and cellular stress. This suggests that astrocytes undergo an acute response following infection observed by a large change in chromatin structure associated with inflammation and immune response genes, which later decrease in accessibility. Motif enrichment analysis provides greater insight into the overall response of astrocytes across time points. The AP-1 transcription factor is involved in the transcription of genes in response to inflammatory stimuli, stress signals, and infection. This transcription factor is made up of a heterodimer that includes the FOS, JUN, ATF, and JDP families. Motif analysis indicated significant enrichment of these family members at each time point, and in fact, analysis of peaks shared amongst all time points indicated AP-1 motif as being the most significantly enriched. These data suggest that the response of astrocytes to B. burgdorferi is in part due to the changes in chromatin accessibility that provides an environment for the transcription of genes associated with the inflammatory and immune response. Furthermore, AP-1 has been implicated as a potential transcription factor responsible for these changes in gene expression. Together, the work within this dissertation demonstrates potential mechanisms for the pathogenesis of neuroborreliosis and PTLDS. This is highlighted by the potential of the choroid plexus as a route of dissemination for B. burgdorferi and peripheral immune cells into the CNS as an explanation for the clinical manifestations of neuroborreliosis. Additionally, these studies are the first to implicate B. burgdorferi as an epimutagen which provides insight into the mechanisms and development of the neurological and persistent symptoms of Lyme disease. In conclusion, this work provides novel insights for the pathogenesis of the neurological effects of Lyme disease which may aid in the development of future therapeutics

Gödel\u27s Incompleteness Theorems

The Incompleteness Theorems of Kurt Godel are very famous both within and outside of mathematics. They focus on independence and consistency within mathematics and hence a more thorough understanding of these is beneficial to their study. The proofs of the theorems involve many ideas which may be unfamiliar to many, including those of formal systems, Godel numbering, and recursive functions and relations. The arguments themselves mirror the Liar’s Paradox in that Godel constructs a statement asserting its own unprovability and then shows that such a statement and its negation must both be independent of the system, otherwise the system is inconsistent. We then proceed to survey various interpretations of the Incompleteness Theorems, focusing on potential misapplications of the theorems

The future of rehabilitation in the United Kingdom National Health Service: Using the COVID-19 crisis to promote change, increasing efficiency and effectiveness

The problem: Rehabilitation services in the UK are inadequate, with insufficient capacity or flexibility to meet the needs of patients after Covid-19. History: Rehabilitation developed in a piecemeal way, focused on specific problems: spinal cord injury, burns, polio, stroke, back pain, equipment and adaptations etc. Rehabilitation is also provided using other names (e.g. intermediate care). Patients with complex needs do not fit easily within this system. System failure: After Covid-19, patients have problems that cross existing condition-specific and/or treatment-specific services. Covid-19 has exposed the lack of any coherent organisational principle underlying development or commissioning of rehabilitation services. Consequently, in order to have their needs met, patients either have to engage with two or more separate services or they receive good management for some problems and sub-optimal management for other problems. The goals: The multitude of small specific services need to coalesce into an integrated service able to meet all the needs of any patient referred. Second, rehabilitation needs to be fully integrated into all healthcare services. A solution: The purpose of healthcare is to ‘improve our health and well-being . . . to stay as well as we can to the end of our lives’. (NHS constitution) All healthcare services need to consider patients holistically, giving equal attention to disease, disability, and distress. Rehabilitation, acute care, mental health and palliative care services need to work in parallel to achieve this purpose. Healthcare providers, supported by commissioners and rehabilitation experts, could achieve structural and organisational change, meeting the needs of patients

What is rehabilitation? An empirical investigation leading to an evidence-based description

Background. There is no agreement about or understanding of what rehabilitation is; those who pay for it, those who provide it, and those who receive it all have different interpretations. Further, within each group, there will a variety of opinions. Definitions based on authority or on theory also vary and do not give a clear description of what someone buying, providing or receiving rehabilitation can actually expect. Method. This editorial extracts information from systematic reviews that find rehabilitation to be effective, to discover the key features and to develop an empirical definition. Findings. The evidence shows that rehabilitation may benefit any person with a longer-lasting disability, arising from any cause, may do so at any stage of the illness, at any age, and may be delivered in any setting. Effective rehabilitation depends on an expert multi-disciplinary team, working within the biopsychosocial model of illness, and working collaboratively towards agreed goals. The effective general interventions include exercise, practice of tasks, education of and self-management by the patient, and psychosocial support. In addition, a huge range of other interventions may be needed, making rehabilitation an extremely complex process; specific actions must be tailored to the needs, goals and wishes of the individual patient, but the consequences of any action are unpredictable, and may not even be those anticipated. Conclusion. Effective rehabilitation is a person-centred process, with treatment tailored to the individual patient’s needs and, importantly, personalised monitoring of changes associated with intervention, with further changes in goals and actions if needed

The Closed Outdoors: A Hiker Quarantines in New York City

“My first impulse was to flee to the mountains.” But that is not happening. A hiker copes with quarantines in New York City. Every day brings new extremes and new tests of this Appalachian Trail thru-hiker’s optimism and sense of humor

Modeling the dynamic behaviours of Francis turbine runner over different steady-state operating conditions

Abstract: Current power systems must adapt to new requirements leading to the need for a better understanding of dynamic behaviors across the full operating range of hydroelectric turbines, especially to assess the impact on the life of critical components like runner blade. However, this information cannot be fully obtained due to limited experimental measurements. Therefore, our research aims to create prediction models which can interpolate or extrapolate the strain/stress signal to generate data over any operating conditions and time duration.Résumé de la communication présentée lors du congrès international tenu conjointement par Canadian Society for Mechanical Engineering (CSME) et Computational Fluid Dynamics Society of Canada (CFD Canada), à l’Université de Sherbrooke (Québec), du 28 au 31 mai 2023