Wordsworth's "Salisbury Plain": an edition of three texts with an essay on their place in the development of his poetry

The thesis is in two parts. The first consists of an edition of the three poems which grew from Wordsworth's experiences on Salisbury plain in 1793. The texts are prefaced by two chapters. The first records the history of the composition of A Night on Salisbury Plain (1793-1795), Adventures on Salisbury Plain (1795-1799) and Guilt and Sorrow (1841-1842) and discusses the nature of Wordsworth's developing conception of the poems. The second describes the manuscripts involved and discusses problems of dating and composition. The texts follow. In the case of the two early poems the text established is that of the earliest complete version, taken from manuscript. In an apparatus crlticus all manuscript revision is recorded. In the case of Guilt and Sorrow the text is that of the first published version, 1842, with an apparatus criticus of all later variants to 1850, the date of the poet's last authorised edition. Supporting material concerning other manuscript work of interest and a possible source for part of Adventures on Salisbury Plain is given in appendices. The second part of the thesis examines the poems and their place in the development of Wordsworth's art as seen from two points of view. The first traces the growth of Wordsworth's ideas on the relationship of man to his world. A movement is followed from A Night on Salisbury Plain where this relationship is conceived in social and political terms only, to The Ruined Cottage where it is conceived in quasi-mystical or philosophic terms. Adventures on Salisbury Plain is seen as the vital transitional poem for here Wordsworth changes the focus of his interest from man the social, political being to man the solitary being who has to come to terms not only with alien social conditions but with himself and his relation to his fellow men. The second point of view sees Wordsworth's development as shaped in part by the need to solve certain problems inherent in didactic writing. The problems are outlined in an introduction and in a study of a passage from An Evening. Walk which suggest the kind of relationship necessary in any didactic work between the poet and the raw materials of his 'message', the imaginative world he creates to project this, and the reader and the world of his own experience and judgment which he brings to bear on the poem. The poems are then examined as evidence of the way in which Wordsworth repeatedly tried to establish the right relationship. The Salisbury Plain are valuable because of the way they make the issues clear to Wordsworth: The Ruined Cottage because of a successful discovery of form, in which the poet can take an acceptable role in his own poem, parallel to the role adopted by the reader

Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank.

Background The causal relevance of elevated blood pressure for several cardiovascular diseases (CVDs) is uncertain, as is the population impact of blood pressure lowering. This study systematically assesses evidence of causality for various CVDs in a 2-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP). Methods and Results We investigated associations of genetically predicted SBP as predicted by 256 genetic variants with 21 CVDs in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376 703 participants of European ancestry, aged 40 to 69 years at recruitment. Genetically predicted SBP was positively associated with 14 of the outcomes (P<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease in a middle-aged to early late-aged UK-based population, population reductions in SBP were predicted to result in an overall 16.9% (95% CI, 12.2%-21.3%) decrease in morbidity for a 5-mm Hg decrease from a population mean of 137.7 mm Hg, 30.8% (95% CI, 22.8%-38.0%) decrease for a 10-mm Hg decrease, and 56.2% (95% CI, 43.7%-65.9%) decrease for a 22.7-mm Hg decrease in SBP (22.7 mm Hg represents a shift from the current mean SBP to 115 mm Hg). Conclusions Risk of many CVDs is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure

Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation.

Lipoprotein(a) (Lp[a]) is a circulating lipoprotein with proatherogenic, proinflammatory, and possibly prothrombotic properties. Circulating Lp(a) levels are largely genetically determined, in particular, by the LPA gene. As such, genetic variants at the LPA locus can serve as instrumental variables for investigating the clinical effects of circulating Lp(a) levels. Mendelian randomization (MR) studies have shown that elevated Lp(a) levels are associated with a higher risk of coronary artery disease1–3 and aortic valve stenosis.2–4 Evidence on the causal role of elevated Lp(a) levels for other atherosclerotic and specific valvular diseases is limited, although there are MR data supporting a positive association between genetically predicted Lp(a) levels and peripheral artery disease.2,3 Whether Lp(a) is causally related to thrombotic disease and cerebrovascular disease remains unclear.2,3,5 In this study, we used the UK Biobank cohort to perform an MR investigation into the causal effects of circulating Lp(a) levels on atherosclerotic, cerebrovascular, thrombotic, and valvular diseases. Because a recent MR study provided evidence of an inverse association of Lp(a) levels with Alzheimer disease,5 we additionally explored whether genetically predicted Lp(a) levels are associated with Alzheimer disease and dementia.Dr Larsson receives support from the Swedish Heart-Lung Foundation (Hjärt-Lungfonden, grant number 20190247), the Swedish Research Council (Vetenskapsrådet, grant number 2019-00977), and the Swedish Research Council for Health, Working Life and Welfare (Forte, grant number 2018-00123). Dr Gill is funded by the Wellcome 4i Clinical PhD Program at Imperial College London. Dr Burgess is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (award number 204623/Z/16/Z). Drs Burgess and Butterworth report funding from Novartis relating to the investigation of lipoprotein(a). The funder had no influence on the content of the investigation or the decision to publish. This work was supported by core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946), the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust] and Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome

An automated quasi-continuous capillary refill timing device

Capillary refill time (CRT) is a simple means of cardiovascular assessment which is widely used in clinical care. Currently, CRT is measured through manual assessment of the time taken for skin tone to return to normal colour following blanching of the skin surface. There is evidence to suggest that manually assessed CRT is subject to bias from ambient light conditions, a lack of standardisation of both blanching time and manually applied pressure, subjectiveness of return to normal colour, and variability in the manual assessment of time. We present a novel automated system for CRT measurement, incorporating three components: a non-invasive adhesive sensor incorporating a pneumatic actuator, a diffuse multi-wavelength reflectance measurement device, and a temperature sensor; a battery operated datalogger unit containing a self contained pneumatic supply; and PC based data analysis software for the extraction of refill time, patient skin surface temperature, and sensor signal quality. Through standardisation of the test, it is hoped that some of the shortcomings of manual CRT can be overcome. In addition, an automated system will facilitate easier integration of CRT into electronic record keeping and clinical monitoring or scoring systems, as well as reducing demands on clinicians. Summary analysis of volunteer (n = 30) automated CRT datasets are presented, from 15 healthy adults and 15 healthy children (aged from 5 to 15 years), as their arms were cooled from ambient temperature to 5°C. A more detailed analysis of two typical datasets is also presented, demonstrating that the response of automated CRT to cooling matches that of previously published studies

Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome

Intestinal helminth infections occur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection

Life-Expectancy Disparities Among Adults With HIV in the United States and Canada: The Impact of a Reduction in Drug- and Alcohol-Related Deaths Using the Lives Saved Simulation Model.

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004-2007, 2008-2011, and 2012-2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004-2007 to 2012-2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with &gt;10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of &gt;10% body weight increase at two years (adjusted odds ratio&nbsp;=&nbsp;1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

The relationship between foot arch measurements and walking parameters in children

BACKGROUND: Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults using dynamic measures. METHODS: Data were collected from 638 participants (n = 254 children and n = 384 adults) at the Museum of Science, Boston (MOS) and from 18 4- to 8-year-olds at the Motor Development and Motor Control Laboratories. Digital footprints were used to calculate two arch indices: the Chippaux-Smirak (CSI) and the Keimig Indices (KI). The height of the navicular bone was measured. Gait parameters were captured with a mechanized gait carpet at the MOS and three-dimensional motion analyses and in-ground force plates in the Motor Development and Motor Control Laboratories. RESULTS: Linear regression analyses on data from the MOS confirmed that as age increases, step length increases. With a linear mixed effect regression model, we found that individuals who took longer steps had higher arches as measured by the KI. However, this relationship was no longer significant when only adults were included in the model. A model restricted to children found that amongst this sample, those with higher CSI and higher KI values take longer relative step lengths. Data from the Motor Development and Motor Control Laboratories showed that both CSI and KI added to the prediction; children with lower anterior ground reaction forces had higher CSI and higher KI values. Arch height indices were correlated with navicular height. CONCLUSIONS: These results suggest that more than one measure of the arch may be needed elucidate the relationship between arch height and gait.K12 HD055931 - NICHD NIH HHS; K12HD055931 - NICHD NIH HH