So Much for Fond Five-Dollar Memories : Prostitution in Las Vegas, 1905-1955

Over the fifty years examined in this thesis, the interactions between federal and local officials shaped prostitution policy in Las Vegas and Clark County. At times that federal authorities were concerned about prostitution in the county, local leaders balanced tradition and economic necessity in their responses. In the early twentieth century, prostitution\u27s benefits to the local economy outweighed fear of federal reprisals, so local officials worked to protect the city\u27s brothels. By the start of World War II, the federal government\u27s increased power and presence in the West made local officials more willing to abandon the tolerance for prostitution in the community and pursue an aggressive campaign of enforcement against suspected prostitutes. In the years immediately after the war, county and city officials undertook a war on vice that targeted brothels that periodically emerged in various parts of the community. Finally, in 1954 a federal raid on one of Southern Nevada\u27s most successful brothels initiated a series of events that led to a permanent end for brothel prostitution in Clark County. This thesis illustrates the connections between two important histories: the growth of Las Vegas from a small railroad town into a modern resort city, and the expansion of the federal government\u27s power and influence during the first half of the twentieth century. Prostitution serves as a lens through which to view how these two narratives are linked

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

Pollinator-flower interactions in gardens during the covid 19 pandemic lockdown of 2020

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential

Pollinator-flower interactions in gardens during the COVID-19 pandemic lockdown of 2020

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential

Pollinator-flower interactions in gardens during the COVID-19 pandemic lockdown of 2020

During the main COVID-19 pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in their gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18o North in Norway to 37.96o South in Australia and resulted in a data set of 25,174 rows long and comprising almost 47,000 visits to flowers, as well as records of plants that were not visited by pollinators. In this first publication from the project we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. As well as producing a data set that we hope will be widely used in the future, the project helped enormously with the health and mental wellbeing of the participants, a by-product of ecological field work that cannot be over-estimated

Pollinator-flower interactions in gardens during the COVID-19 pandemic lockdown of 2020

During the main COVID-19 pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in their gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18o North in Norway to 37.96o South in Australia and resulted in a data set of 25,174 rows long and comprising almost 47,000 visits to flowers, as well as records of plants that were not visited by pollinators. In this first publication from the project we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. As well as producing a data set that we hope will be widely used in the future, the project helped enormously with the health and mental wellbeing of the participants, a by-product of ecological field work that cannot be over-estimated

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR