Nietzsche's aestheticist claim: on the relation between art and truth

Nietzsche's controversial "aestheticist" claim that existence and the world are only justifiable as aesthetic phenomena provides the motivation for this thesis. The aestheticist claim is summative of Nietzsche's characteristic aestheticism, which allows for a link between the typically distinct concepts of art and truth. Although the available literature includes analysis of Nietzsche's aestheticism, no full defence of it has previously been offered. The general view seems to be that aestheticism should be treated sceptically, and as such, it remains underdeveloped within contemporary Nietzsche studies. The chief aims of the thesis are therefore to respond to this relative neglect of the aestheticist view of the art/truth relation, and to develop and defend a standard account of aestheticism. Additionally, in so doing the thesis aims to offer implicit evidence of Nietzsche's philosophy as continuous in order to raise the question of the textual periodisation technique, which lends methodological weight to the sceptical attitude towards Nietzsche's aestheticism. The question of aestheticism is contextualised within the 'Two Cultures' debate on the relation between art, truth and science and the nihilistic crisis of values in modern culture. As such, the wider significance of defending Nietzsche's aestheticism is made appreciable. Following analysis of the available readings of aestheticism, key elements are considered and the features of a standard account are identified. However, three problems which turn on issues surrounding the art/truth relation in Nietzsche are also identified: the problems of metaphysics, ethics and common ontological ground. The thesis proposes solutions to each of these in turn. Nietzsche's aestheticism is therefore defended by appeal to an interpretative link between art and truth in the terms of Nietzsche's conception of being

Lipopolysaccharide as a major virulence factor in the pathogenesis of Burkholderia cepacia syndrome

In cystic fibrosis (CF), bacteria of the Burkholderia cepacia complex (Bcc) can induce a fulminant inflammation with pneumonitis and sepsis. Lipopolysaccharide (LPS) may be an important virulence factor associated with the increased morbidity and mortality seen in Bcc infection but little is known about the molecular pathogenesis of Bcc LPS. In this study, the inflammatory response to highly purified LPS from different Bcc clinical isolates and the cellular signalling pathways employed was investigated. It has been suggested that the large inflammatory response from BcLPS may be due to contaminants in the LPS preparation. Phenol-chloroform petroleum ether (PCP) purified BcLPS preparations were compared to more highly purified, enzyme treated preparations of BcLPS. There were no significant differences in the levels of IL-6 and TNF-a induced from monocytes (MM6) and in levels of IL-8 from epithelial cells (A549), which indicates that there were no contaminants present that could cause an inflammatory response from these cells. The inflammatory response elicited by LPS from different Bcc species that were tested was seen to be varied. LPS from different clinical isolates of the same clonal ET12 strain of Burkholderia cenocepacia were found to induce a varied inflammatory response. Some isolate's LPS produced as much cytokine as prototypical Escherichia coli LPS and all Bcc isolates tested with the exception of environmental samples produced higher levels of inflammatory cytokine than LPS from the CF pathogen Pseudomonas aeruginosa. It was shown that passaging over time under laboratory conditions was not responsible for this variation. Bcc LPS samples were tested in their ability to prime MM6 cells for respiratory burst, samples that had previously produced high levels of cytokine from direct stimulation of MM6 cells were found to not be the most efficient primers of respiratory burst. It was found that the inflammatory response from Bcc LPS stimulated monocytes was separate and in some cases opposite to the ability to prime for respiratory burst. Inhibition experiments were used to investigate the Toll-like receptors and associated adaptor molecules and pathways utilized when monocytes were stimulated by Bcc LPS. The use of anti-CD14, anti-TLR4 and anti-TLR2 antibodies in Bcc LPS stimulated monocytes showed that all Bcc LPS samples tested signalled via CD 14 and TLR4 and not via TLR2. Inhibition of MyD88 using an inhibitor peptide proved that all but one sample required MyD88 to signal. LPS from clinical isolate of Burkholderia multivorans was found to activate the inflammatory response via MyD88-independent pathways. Using MAP kinase inhibitors to test for reduction of cytokine response from stimulated MM6 cells and direct analysis of activation through western blotting, LPS from all clinical Bcc isolates were seen to activate all three major MAPKs p42/44, p38 and JNK. Degradation of the NF-kB inhibitory protein IicB-a was tested using anti-lKB-a antibodies and activation of the transcription factor NF-kB was tested using an electrophoretic mobility shift assay (EMSA). IicB-a was degraded and NF-kB was activated in all the BcLPS samples tested. This study suggests that LPS alone from clinical isolates of Bcc is major virulence factor in CF that it can cause a massive inflammatory response from cells, and that the LPS induced signalling cascade is via classical TLR4-mediated signalling pathways similar to highly inflammatory LPS purified from E.coli.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Lipopolysaccharide as a major virulence factor in the pathogenesis of Burkholderia cepacia syndrome

In cystic fibrosis (CF), bacteria of the Burkholderia cepacia complex (Bcc) can induce a fulminant inflammation with pneumonitis and sepsis. Lipopolysaccharide (LPS) may be an important virulence factor associated with the increased morbidity and mortality seen in Bcc infection but little is known about the molecular pathogenesis of Bcc LPS. In this study, the inflammatory response to highly purified LPS from different Bcc clinical isolates and the cellular signalling pathways employed was investigated. It has been suggested that the large inflammatory response from BcLPS may be due to contaminants in the LPS preparation. Phenol-chloroform petroleum ether (PCP) purified BcLPS preparations were compared to more highly purified, enzyme treated preparations of BcLPS. There were no significant differences in the levels of IL-6 and TNF-a induced from monocytes (MM6) and in levels of IL-8 from epithelial cells (A549), which indicates that there were no contaminants present that could cause an inflammatory response from these cells. The inflammatory response elicited by LPS from different Bcc species that were tested was seen to be varied. LPS from different clinical isolates of the same clonal ET12 strain of Burkholderia cenocepacia were found to induce a varied inflammatory response. Some isolate's LPS produced as much cytokine as prototypical Escherichia coli LPS and all Bcc isolates tested with the exception of environmental samples produced higher levels of inflammatory cytokine than LPS from the CF pathogen Pseudomonas aeruginosa. It was shown that passaging over time under laboratory conditions was not responsible for this variation. Bcc LPS samples were tested in their ability to prime MM6 cells for respiratory burst, samples that had previously produced high levels of cytokine from direct stimulation of MM6 cells were found to not be the most efficient primers of respiratory burst. It was found that the inflammatory response from Bcc LPS stimulated monocytes was separate and in some cases opposite to the ability to prime for respiratory burst. Inhibition experiments were used to investigate the Toll-like receptors and associated adaptor molecules and pathways utilized when monocytes were stimulated by Bcc LPS. The use of anti-CD14, anti-TLR4 and anti-TLR2 antibodies in Bcc LPS stimulated monocytes showed that all Bcc LPS samples tested signalled via CD 14 and TLR4 and not via TLR2. Inhibition of MyD88 using an inhibitor peptide proved that all but one sample required MyD88 to signal. LPS from clinical isolate of Burkholderia multivorans was found to activate the inflammatory response via MyD88-independent pathways. Using MAP kinase inhibitors to test for reduction of cytokine response from stimulated MM6 cells and direct analysis of activation through western blotting, LPS from all clinical Bcc isolates were seen to activate all three major MAPKs p42/44, p38 and JNK. Degradation of the NF-kB inhibitory protein IicB-a was tested using anti-lKB-a antibodies and activation of the transcription factor NF-kB was tested using an electrophoretic mobility shift assay (EMSA). IicB-a was degraded and NF-kB was activated in all the BcLPS samples tested. This study suggests that LPS alone from clinical isolates of Bcc is major virulence factor in CF that it can cause a massive inflammatory response from cells, and that the LPS induced signalling cascade is via classical TLR4-mediated signalling pathways similar to highly inflammatory LPS purified from E.coli

Galapagos-2/Galfitm/Gama – Multi-wavelength measurement of galaxy structure: Separating the properties of spheroid and disk components in modern surveys

Aims. We present the capabilities of GALAPAGOS-2 and GALFITM in the context of fitting two-component profiles – bulge–disk decompositions – to galaxies, with the ultimate goal of providing complete multi-band, multi-component fitting of large samples of galaxies in future surveys. We also release both the code and the fit results to 234 239 objects from the DR3 of the GAMA survey, a sample significantly deeper than in previous works. Methods. We use stringent tests on both simulated and real data, as well as comparison to public catalogues to evaluate the advantages of using multi-band over single-band data. Results. We show that multi-band fitting using GALFITM provides significant advantages when trying to decompose galaxies into their individual constituents, as more data are being used, by effectively being able to use the colour information buried in the individual exposures to its advantage. Using simulated data, we find that multi-band fitting significantly reduces deviations from the real parameter values, allows component sizes and Sérsic indices to be recovered more accurately, and – by design – constrains the band-to-band variations of these parameters to more physical values. On both simulated and real data, we confirm that the spectral energy distributions (SEDs) of the two main components can be recovered to fainter magnitudes compared to using single-band fitting, which tends to recover ‘disks’ and ‘bulges’ with – on average – identical SEDs when the galaxies become too faint, instead of the different SEDs they truly have. By comparing our results to those provided by other fitting codes, we confirm that they agree in general, but measurement errors can be significantly reduced by using the multi-band tools developed by the MEGAMORPH project. Conclusions. We conclude that the multi-band fitting employed by GALAPAGOS-2 and GALFITM significantly improves the accuracy of structural galaxy parameters and enables much larger samples to be be used in a scientific analysis

Best Practices in Training Caregivers to Implement Behavioral Interventions

It has been well documented in the literature that behavioral interventions are effective in reducing a wide variety of maladaptive behaviors such as aggression, self-injury and destructive behaviors (Allen & Warzak, 2000; Campbell, 2003). Despite the success of these interventions, they are often implemented in tightly controlled settings with third party individuals that are able to implement procedures with a high degree of integrity (Fryling, 2014). Due to the complexities of the natural environment, caregivers may be less likely to implement behavioral interventions with the same degree of integrity and have limited available time for training on procedures. Therefore, it is important to evaluate efficient and effective strategies for caregiver training. This presentation will review common challenges to caregiver training and outline procedures for caregiver training that are aimed at decreasing the time needed as well as increasing caregiver treatment integrity. Specifically, the advantages and disadvantages of didactics, role play and in vivo instruction will be discussed

Galaxy And Mass Assembly (GAMA) : refining the local galaxy merger rate using morphological information

KRVS acknowledges the Science and Technology Facilities Council (STFC) for providing funding for this project, as well as the Government of Catalonia for a research travel grant (ref. 2010 BE-00268) to begin this project at the University of Nottingham. PN acknowledges the support of the Royal Society through the award of a University Research Fellowship and the European Research Council, through receipt of a Starting Grant (DEGAS-259586).We use the Galaxy And Mass Assembly (GAMA) survey to measure the local Universe mass-dependent merger fraction and merger rate using galaxy pairs and the CAS (concentration, asymmetry, and smoothness) structural method, which identifies highly asymmetric merger candidate galaxies. Our goals are to determine which types of mergers produce highly asymmetrical galaxies and to provide a new measurement of the local galaxy major merger rate. We examine galaxy pairs at stellar mass limits down to M* = 108 M⊙ with mass ratios of 4:1) the lower mass companion becomes highly asymmetric, whereas the larger galaxy is much less affected. The fraction of highly asymmetric paired galaxies which have a major merger companion is highest for the most massive galaxies and drops progressively with decreasing mass. We calculate that the mass-dependent major merger fraction is fairly constant at ∼1.3–2 per cent within 109.5 < M* < 1011.5 M⊙, and increases to ∼4 per cent at lower masses. When the observability time-scales are taken into consideration, the major merger rate is found to approximately triple over the mass range we consider. The total comoving volume major merger rate over the range 108.0 < M* < 1011.5 M⊙ is (1.2 ± 0.5) × 10−3 h370 Mpc−3 Gyr−1.Publisher PDFPeer reviewe

Galapagos-2/Galfitm/Gama - Multi-wavelength measurement of galaxy structure: Separating the properties of spheroid and disk components in modern surveys

Aims. We present the capabilities of Galapagos-2 and Galfitm in the context of fitting two-component profiles - bulge- disk decompositions - to galaxies, with the ultimate goal of providing complete multi-band, multi-component fitting of large samples of galaxies in future surveys. We also release both the code and the fit results to 234 239 objects from the DR3 of the GAMA survey, a sample significantly deeper than in previous works. Methods. We use stringent tests on both simulated and real data, as well as comparison to public catalogues to evaluate the advantages of using multi-band over single-band data. Results. We show that multi-band fitting using Galfitm provides significant advantages when trying to decompose galaxies into their individual constituents, as more data are being used, by effectively being able to use the colour information buried in the individual exposures to its advantage. Using simulated data, we find that multi-band fitting significantly reduces deviations from the real parameter values, allows component sizes and Sérsic indices to be recovered more accurately, and - by design - constrains the band-to-band variations of these parameters to more physical values. On both simulated and real data, we confirm that the spectral energy distributions (SEDs) of the two main components can be recovered to fainter magnitudes compared to using single-band fitting, which tends to recover disks'and bulges'with - on average - identical SEDs when the galaxies become too faint, instead of the different SEDs they truly have. By comparing our results to those provided by other fitting codes, we confirm that they agree in general, but measurement errors can be significantly reduced by using the multi-band tools developed by the MEGAMORPH project. Conclusions. We conclude that the multi-band fitting employed by Galapagos-2 and Galfitm significantly improves the accuracy of structural galaxy parameters and enables much larger samples to be be used in a scientific analysis

Galaxy and Mass Assembly (GAMA): ugriz galaxy luminosity functions

Galaxy and Mass Assembly (GAMA) is a project to study galaxy formation and evolution, combining imaging data from ultraviolet to radio with spectroscopic data from the AAOmega spectrograph on the Anglo-Australian Telescope. Using data from Phase 1 of GAMA, taken over three observing seasons, and correcting for various minor sources of incompleteness, we calculate galaxy luminosity functions (LFs) and their evolution in the ugriz passbands. At low redshift, z < 0.1, we find that blue galaxies, defined according to a magnitude-dependent but non-evolving colour cut, are reasonably well fitted over a range of more than 10 magnitudes by simple Schechter functions in all bands. Red galaxies, and the combined blue plus red sample, require double power-law Schechter functions to fit a dip in their LF faintwards of the characteristic magnitude M* before a steepening faint end. This upturn is at least partly due to dust-reddened disc galaxies. We measure the evolution of the galaxy LF over the redshift range 0.002 < z < 0.5 both by using a parametric fit and by measuring binned LFs in redshift slices. The characteristic luminosity L* is found to increase with redshift in all bands, with red galaxies showing stronger luminosity evolution than blue galaxies. The comoving number density of blue galaxies increases with redshift, while that of red galaxies decreases, consistent with prevailing movement from blue cloud to red sequence. As well as being more numerous at higher redshift, blue galaxies also dominate the overall luminosity density beyond redshifts z≃ 0.2. At lower redshifts, the luminosity density is dominated by red galaxies in the riz bands, and by blue galaxies in u and g

Improving primary care based post-diagnostic support for people living with dementia and carers: Developing a complex intervention using the Theory of Change

BACKGROUND: The need to improve support following a diagnosis of dementia is widely recognised, but it is unclear how this can best be achieved within UK health and social care systems. A task-shared and task-shifted approach has been recommended, but there is limited guidance on how to achieve this in practice. As part of a programme of research, we developed an intervention to enhance the role of primary care in post-diagnostic care and support for people living with dementia and carers. METHODS: We used the Theory of Change to develop a complex intervention informed by initial literature reviews and qualitative work. The intervention was developed through an iterative series of workshops, meetings and task groups with a range of stakeholders, including the multidisciplinary project team, people living with dementia and carers, service managers, frontline practitioners, and commissioners. RESULTS: 142 participants contributed to intervention development through face-to-face or virtual meetings. The intervention comprises three complementary strands of work focusing on: developing systems, delivering tailored care and support, and building capacity and capability. Clinical dementia leads, based in primary care networks, will facilitate the intervention providing tailored expertise and support. CONCLUSION: The Theory of Change proved useful in providing structure and engaging stakeholders. The process was challenging, took longer and was less participative than intended due to restrictions caused by the COVID-19 pandemic. We will next conduct a feasibility and implementation study to explore whether the intervention can be successfully delivered within primary care. If successful, the intervention offers practical strategies for delivering a task-shared and task-shifted approach to post-diagnostic support that could be adapted for similar health and social care contexts internationally

A polymorphic residue that attenuates the antiviral potential of interferon lambda 4 in hominid lineages

As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses. Counter-intuitively, expression of one member of the family, IFNλ4, is associated with decreased clearance of hepatitis C virus (HCV) in the human population; by contrast, a natural frameshift mutation that abrogates IFNλ4 production improves HCV clearance. To further understand how genetic variation between and within species affects IFNλ4 function, we screened a panel of all known extant coding variants of human IFNλ4 for their antiviral potential and identify three that substantially affect activity: P70S, L79F and K154E. The most notable variant was K154E, which was found in African Congo rainforest ‘Pygmy’ hunter-gatherers. K154E greatly enhanced in vitro activity in a range of antiviral (HCV, Zika virus, influenza virus and encephalomyocarditis virus) and gene expression assays. Remarkably, E154 is the ancestral residue in mammalian IFNλ4s and is extremely well conserved, yet K154 has been fixed throughout evolution of the hominid genus Homo, including Neanderthals. Compared to chimpanzee IFNλ4, the human orthologue had reduced activity due to amino acid K154. Comparison of published gene expression data from humans and chimpanzees showed that this difference in activity between K154 and E154 in IFNλ4 correlates with differences in antiviral gene expression in vivo during HCV infection. Mechanistically, our data show that the human-specific K154 negatively affects IFNλ4 activity through a novel means by reducing its secretion and potency. We thus demonstrate that attenuated activity of IFNλ4 is conserved among humans and postulate that differences in IFNλ4 activity between species contribute to distinct host-specific responses to—and outcomes of—infection, such as HCV infection. The driver of reduced IFNλ4 antiviral activity in humans remains unknown but likely arose between 6 million and 360,000 years ago in Africa