William Dodsworth 1798-1861: the origins of Tractarian thought and practice in London

This thesis presents William Dodsworth as a central figure in the transmission of Tractarian ideas from Oxford to London. His career reveals a unique interface between radical Evangelicalism and the first impact of the Oxford Movement on the religious life of the capital. Dodsworth's formation is set within the variety of religious responses produced by the ideological upheaval consequent upon the French Revolution, and in particular the revival of adventism. His life-long quest for a unified theological system that would resist liberalism in church and state underlies his early involvement in the prophetic studies movement, and his enduring commitment to pre-millennialism. Dodsworth's adventism is the key to his development from Evangelical, through Tractarianism to the Roman Catholic Church. The impetus for this evolution can be traced to his association with Edward Irving and his circle. Irving's eschatology and reinterpretation of traditional Evangelicalism led Dodsworth to an incarnation-centred soteriology which enabled him to develop a new 'Catholic' ecclesiology worked out in his preaching and sacramental practice at the Margaret Chapel from 1829. Distanced from Irving and drawn into the incipient Tractarian Movement, Dodsworth's potential for leadership was recognised by Newman, and utilized by Pusey in the establishment of Christ Church, Albany Street as a prototype of the Anglo-Catholic parish, and a first embodiment of the Oxford Movement's pastoral ideals in London. Evaluation of Dodsworth's ministry, preaching and publications not only calls for a reappraisal of his hitherto obscured place in Anglo-Catholic history, but demands a reexamination of the origins of Tractarianism in the capital and especially its relationship to contemporary Evanglicalism. This thesis concludes with a critique of Dodsworth's contribution as an Anglican convert to the Roman Catholic Church, and offers him as a promising subject for future study of nineteenth century religious history

The novel design of an energy efficient superconductor-based series reactor for installation at a grid connected research site

This paper proposes the development of a superconducting series reactor (SSR) as an alternative to traditionally employed technologies and superconducting fault current limiters when managing fault levels on the electrical power grid. By utilizing superconducting tape, which has negligible resistance, in the construction of a series reactor, it is proposed that fault level mitigation could be achieved in a more energy efficient manner. Once constructed the SSR will be installed and tested at a grid-connected power engineering research site, and the proposed impact of this installation is firstly simulated using Reticmaster® power system simulation software. Design parameters for the prototype SSR are then calculated enabling the total cost of the modifications and prototype SSR to be determined. A desktop SSR was also constructed and tested as a pre-cursor to the prototype construction to confirm functionality and design and was found to be up to four times more energy efficient as the equivalent copper reactor. Finally, the calorimetric method of power loss determination was investigated and experimentally shown to be a viable alternative to the traditional electrical method of power loss determination. In the past, the relatively cheap cost of electricity in South Africa had favoured the installation of poor power efficiency devices that required a lower initial capital investment. With increasing energy costs and a focus on carbon emission reductions, the development of the SSR augurs a new era in power system engineering in which designs are proposed considering both total lifecycle costs and energy efficiency. Design proposal for the first superconducting power device in Africa Alternative to less efficient fault current management technologies currently employed Construction and testing of a desktop superconducting series reactor Verification of the calorimetric method for power loss determination

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study.

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question

Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage

HIV/AIDS, demography and development: individual choices versus public policies in SSA

Despite the increasing rate of diffusion of effective therapies, the battle against HIV/AIDS in Sub-Saharan Africa (SSA) is far from being over. Three main challenges are that the epidemics might paralyse or reverse the fertility transition, the expansion of the resources needed to finance the fight against HIV, and the emerging resistance to anti-retroviral treatments. This research proposes a UGT-like model showing the complexity of the interplay amongst the (macro)economy, the epidemics, their endogenous feedback on mortality and fertility and the central role of policy actions aimed to fight HIV. The disease-induced increase in adult mortality can hamper economic development by its upward pressure on the precautionary demand for children and downward pressure on education. This can dramatically reduce physical and human capital accumulation

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

A survey of microRNA single nucleotide polymorphisms identifies novel breast cancer susceptibility loci in a case-control, population-based study of African-American women

Abstract Background MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor subtype among African-American (AA) women. Methods Under the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, genotyping and imputed data from four studies on BC in AA women were combined into a final dataset containing 224,188 miRNA gene single nucleotide polymorphisms (SNPs) for 8350 women: 3663 cases and 4687 controls. The primary miRNA sequence was identified for 566 miRNA genes expressed in Encyclopedia of DNA Elements (ENCODE) Tier 1 cell types and human pancreatic islets. Association analysis was conducted using logistic regression for BC status overall and by tumor subtype. Results A novel BC signal was localized to an 8.6-kb region of 17q25.3 by four SNPs (rs9913477, rs1428882938, rs28585511, and rs7502931) and remained statistically significant after multiple test correction (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.26–1.65; p = 3.15 × 10−7; false discovery rate (FDR) = 0.03). These SNPs reside in a genomic location that includes both the predicted primary transcript of the noncoding miRNA gene MIR3065 and the first intron of the gene for brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2). Furthermore, miRNA-associated SNPs on chromosomes 1p32.3, 5q32, and 3p25.1 were the strongest signals for hormone receptor, luminal versus basal-like, and HER2 enrichment status, respectively. A second phase of genotyping (1397 BC cases, 2418 controls) that included two SNPs in the 8.6-kb region was used for validation and meta-analysis. While neither rs4969239 nor rs9913477 was validated, when meta-analyzed with the original dataset their association with BC remained directionally consistent (OR = 1.29, 95% CI = 1.16–1.44 (p = 4.18 × 10–6) and OR = 1.33, 95% CI = 1.17–1.51 (p = 1.6 × 10–5), respectively). Conclusion Germline genetic variation indicates that MIR3065 may play an important role in BC development and heterogeneity among AA women. Further investigation to determine the potential functional effects of these SNPs is warranted. This study contributes to our understanding of BC risk in AA women and highlights the complexity in evaluating variation in gene-dense regions of the human genome.https://deepblue.lib.umich.edu/bitstream/2027.42/144216/1/13058_2018_Article_964.pd