9 research outputs found
Early premiership of Lord Liverpool 1812-15 : palma non sine pulvere
Robert Banks Jenkinson, 2nd Earl of Liverpool KG (1770-1828), was First Lord of the
Treasury and Prime Minister for almost fifteen years in the early nineteenth century.
He survived in the premiership for longer than all but two of his predecessors and
longer than all of his successors, at least so far. Liverpool is, however, one the most
overlooked and underestimated of Prime Ministers. Norman Gash's book is the first
and so far only modem biography of Liverpool. This study, however, is less than
three hundred pages in length, is based on only seven of the hundreds of volumes of
the Liverpool Papers in the custody of the British Library and is far from exhaustive
in its use of printed sources. There is evidently considerable scope and need for
further research on the subject of Liverpool's life and career especially during the
period of his premiership and based on a trawl through all the manuscript sources now
available. This doctoral dissertation seeks to examine Liverpool during his early
premiership between 1812 and 1815, one of the least studied but most significant
periods of both Liverpool's life and career, and his administration, from the point
Liverpool succeeded to the highest office to the resettlement of Europe after the long
war with France. The opening section aims to place Liverpool in his historical
context. There is a particular emphasis here on an analysis of the political system that
Liverpool was required to master. Liverpool's early life and career before he rose to
the premiership is the focus of the next section. The main body of the thesis is divided
into two parts. One part examines Liverpool during his early premiership in a mainly
chronological style and is concerned almost entirely with the issues of war and peace,
and the other part seeks to examine a number of major themes that are most
satisfactorily looked at in isolation from the main narrative. For example, one chapter
covers the premier's relationship with the monarchy
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe
The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class
mission concept that will provide essential contributions to multimessenger
astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in
the 200 keV to 10 GeV energy range with a wide field of view, good spectral
resolution, and polarization sensitivity. Therefore, AMEGO is key in the study
of multimessenger astrophysical objects that have unique signatures in the
gamma-ray regime, such as neutron star mergers, supernovae, and flaring active
galactic nuclei. The order-of-magnitude improvement compared to previous MeV
missions also enables discoveries of a wide range of phenomena whose energy
output peaks in the relatively unexplored medium-energy gamma-ray band
Multiple loci on 8q24 associated with prostate cancer susceptibility
Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility
Identification of seven new prostate cancer susceptibility loci through a genome-wide association study
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)
All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe
Astro2020 APC White PaperThe All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band
Genomic reconstruction of the SARS-CoV-2 epidemic in England
AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p