A world for the subject and a world of witnesses for the evidence : developments in geographical literature and the travel narrative in seventeenth-century England

In the latter half of the seventeenth century, the first-person overseas voyage narrative enjoyed an unprecedented degree of popularity in England. This thesis is concerned with texts written by travellers and the increasing perception that such information might be useful to those engaged in newly-developing scientific specialisms. It draws upon a wide range of texts including geographiae, physico-theological texts, first-person voyage narratives and imaginary voyage prose fictions. The main focus of the thesis is on the movement away from traditional encyclopaedic geographical textbooks whose treatment of non-European countries comprised an amalgam of unattributed information and a mass of traditional and erudite beliefs, towards a priontising of eyewitness accounts by named observers. Following an introductory survey of the production of an indigenous body of geographical literature in England, the first chapter traces the decline in popularity of traditional geographiae and the separation of regional description from general theories of the earth. The second chapter shows how in the Restoration period the concerted efforts of Fellows of the newly-established Royal Society resulted in a significant increase in the number of overseas travel narratives being published. The third chapter looks at the way in which the Royal Society's campaign developed from its initiation in 1666 to the close of the century, focusing on the response of travellers to the Society's requests for information. The fourth chapter considers the way in which earlier accounts were advertised as fulfilling contemporary expectations of this type of discourse. The fifth and sixth chapters concern fictitious voyage narratives. Imitative of a genre the value of which was increasingly seen as residing in its veracity, these fictions adapted in accordance with the changes being introduced to real voyage accounts whilst continuing to perpetuate the archaic myths and traditional beliefs which had been ehminated from factual geographical description. Appended to the thesis is a list of accounts of voyages and travels outside Europe, printed in the Philosophical Transactions (1665-1700). Also listed are reviews and abstracts of geographical texts, inquiries concerning specific locations and directions and instructions aimed at seamen, with brief biographical information about the authors to indicate the range of contributors to that journal

Self-reported difficulties with everyday function, cognitive symptoms, and cognitive function in people with HIV

BACKGROUND: We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive (HIV+) adults in five European clinics. METHODS: HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in five domains, psychosocial factors and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment. RESULTS: 448 patients completed the assessments (mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed [HIV-1 plasma RNA <50 copies/mL]). Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment. CONCLUSION: Patients' own assessments of everyday function and symptoms were associated with objectively-measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies

Causes of Multiple Sclerosis: a functional genomics approach

Multiple Sclerosis (MS) is the most common disabling neurological disease affecting young adults in Western Society. To date, 55 strongly associated single nucleotide polymorphisms have been discovered. We now need to identify causal genes. While T-cells as targets for therapeutic intervention have rarely proven useful, there is strong clinical and in-vitro data identifying NK cell deficiencies in patients, and key roles for monocytes in myelin and axon destruction and autoantigen presentation. RNA extracted from magnetic bead sorted monocytes and NK cells, of healthy controls (HC) and untreated patients with relapsing remitting MS (RRMS), was labelled and hybridised to Affymetrix Human Gene 1.0 ST arrays. Expression values were standardized across chips using RMA and quantile normalization as implemented in GenePattern. Genes were ranked by expression difference significance by Mann Whitney U test and ANOVA. To date, we have analysed monocytes of 30 patients and 39 HC, and NK cells from 25 patients and 32 HC. Expression differences of those genes adjacent to MS associated risk SNPs lying between 110kb upstream and 40kb downstream of a candidate gene were considered. We have identified three genes worthy of further analysis on this basis: RGS1, HHEX and THEMIS. To test the relevance of these candidates to central nervous system (CNS) autoimmunity, we aim to mimic phenotypes associated with these expression quantitative trait loci (eQTL) in in-vitro cultures of purified NK cells and monocytes, and in-vivo in a mouse model of MS - experimental autoimmune encephalomyelitis (EAE)

The EDIBLES survey:VI. Searching for time variations of interstellar absorption features

Context. Interstellar absorption observed toward stellar targets changes slowly over long timescales, mainly due to the proper motion of the background target relative to the intervening clouds, such that over time, different parts of the intervening cloud are probed. On longer timescales, the slowly changing physical and chemical conditions in the cloud can also cause variation. Detecting such time variations thus provides an opportunity to study cloud structure.Aims. We searched for systematic variations in the absorption profiles of the diffuse interstellar bands (DIBs) and interstellar atomic and molecular lines by comparing the high-quality data set from the recent ESO diffuse interstellar bands large exploration survey (EDIBLES) to older archival observations, bridging typical timescales of ~10 yr with a maximum timescale of 22 yr.Methods. For 64 EDIBLES targets, we found adequate archival observations. We selected 31 strong DIBs, seven atomic lines, and five molecular lines to focus our search on. We carefully considered various systematic effects and used a robust Bayesian quantitative test to establish which of these absorption features could display significant variations.Results. While systematic effects greatly complicate our search, we find evidence for variations in the profiles of the λλ4727 and 5780 DIBs in a few sightlines. Toward HD 167264, we find a new Ca I cloud component that appears and becomes stronger after 2008. The same sightline furthermore displays marginal, but systematic changes in the column densities of the atomic lines originating from the main cloud component in the sightline. Similar variations are seen toward HD 147933.Conclusions. Our high-quality spectroscopic observations in combination with archival data show that it is possible to probe interstellar time variations on time scales of typically a decade. Despite the fact that systematic uncertainties as well as the generally somewhat lower quality of older data complicate matters, we can conclude that time variations can be made visible, both in atomic lines and DIB profiles for a few targets, but that generally, these features are stable along many lines of sight. We present this study as an archival baseline for future comparisons, bridging longer periods.<br/

Multi-technique investigation of the binary fraction among A-F type candidate hybrid variable stars discovered by Kepler

Hundreds of candidate hybrid pulsators of intermediate type A-F were revealed by the recent space missions. Hybrid pulsators allow to study the full stellar interiors, where p- and g-modes are simultaneously excited. The true hybrid stars must be identified since other processes, due to stellar multiplicity or rotation, might explain the presence of (some) low frequencies observed in their periodograms. We measured the radial velocities of 50 candidate Delta Sct - Gamma Dor hybrid stars from the Kepler mission with the Hermes/Ace spectrographs over a span of months to years. We aim to derive the fraction of binary and multiple systems and to provide an independent and homogeneous determination of the atmospheric properties and vsini for all targets. The objective is to identify the physical cause of the low frequencies. We computed 1-D cross-correlation functions (CCFs) in order to find the best parameters in terms of the number of components, spectral type and vsini for each target. Radial velocities were measured from spectrum synthesis and by using a 2-D cross-correlation technique in the case of double- and triple-lined systems. Fundamental parameters were determined by fitting (composite) synthetic spectra to the normalised median spectra corrected for the appropriate Doppler shifts. We report on the analysis of 478 high-resolution Hermes and 41 Ace spectra of A/F-type candidate hybrid pulsators from the Kepler field. We determined their radial velocities, projected rotational velocities, atmospheric properties and classified our targets based on the shape of the CCFs and the temporal behaviour of the radial velocities. We derived orbital solutions for seven new systems. Three long-period preliminary orbital solutions are confirmed by a photometric time-delay analysis. Finally, we determined a global multiplicity fraction of 27% in our sample of candidate hybrid stars