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

Level of agreement between frequently used cardiovascular risk calculators in people living with HIV

Objectives The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). Methods PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into ‘low’ ( 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots. Results The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range. Conclusions Estimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone

Validation of a novel multivariate method of defining HIV-associated cognitive impairment

Background. The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods. Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results. The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion. Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer selfreported health status. This may be due to the statistical advantage of using a multivariate approac

Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls

We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV-negative people were mediated or moderated by depressive symptoms and lifestyle factors. METHODS: A cross-sectional study of 637 'older' PLWH aged ≥ 50 years, 340 'younger' PLWH aged < 50 years and 276 demographically matched HIV-negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z-scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z-score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ-9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education. RESULTS: After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV-negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV-negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV-negative controls remained significant (P = 0.01). CONCLUSIONS: Poorer cognitive performances in PLWH compared with HIV-negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH

Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53–63) and 58 (53–63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders

Magnetic resonance imaging of cerebral small vessel disease in men living with HIV and HIV-negative men aged 50 and above

We assessed whether HIV status was associated with white matter hyperintensities (WMH), a neuroimaging correlate of cerebral small vessel disease (CSVD), in men aged ≥50 years. A cross-sectional substudy was nested within a larger cohort study. Virologically suppressed men living with HIV (MLWH) and demographically matched HIV-negative men aged ≥50 underwent magnetic resonance imaging (MRI) at 3 Tesla. Sequences included volumetric three-dimensional (3D) T1-weighted, fluid-attenuated inversion recovery and pseudocontinuous arterial spin labeling. Regional segmentation by automated image processing algorithms was used to extract WMH volume (WMHV) and resting cerebral blood flow (CBF). The association between HIV status and WMHV as a proportion of intracranial volume (ICV; log-transformed) was estimated using a multivariable linear regression model. Thirty-eight MLWH [median age 59 years (interquartile range, IQR 55–64)] and 37 HIV-negative [median 58 years (54–63)] men were analyzed. MLWH had median CD4+ count 570 (470–700) cells/μL and a median time since diagnosis of 20 (14–24) years. Framingham 10-year risk of cardiovascular disease was 6.5% in MLWH and 7.4% in controls. Two (5%) MLWH reported a history of stroke or transient ischemic attack and five (13%) reported coronary heart disease compared with none of the controls. The total WMHV in MLWH was 1,696 μL (IQR 1,229–3,268 μL) or 0.10% of ICV compared with 1,627 μL (IQR 1,032–3,077 μL), also 0.10% of ICV in the HIV-negative group (p = .43). In the multivariable model, WMHV/ICV was not associated with HIV status (p = .86). There was an age-dependent decline in cortical CBF [−3.9 mL/100 mL/min per decade of life (95% confidence interval 1.1–6.7 mL)] but no association between CBF and HIV status (p > .2 in all brain regions analyzed). In conclusion, we found no quantitative MRI evidence of an increased burden of CSVD in MLWH aged 50 years and older