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The David W. Fentress Family Letters, 1856-1969
No full textTranscript of a letter by an unidentified author to David Fentress regarding sharing federal newspapers and the banning of federal newspapers in some areas. The author passes on the news of the war including the destruction of the Federal merchantmen by the Confederate fleet. He passes along world news: Russia preparing to go to War with Europe and how that could negatively affect the Confederacy. There is also speculation on the future of the war
The David W. Fentress Family Letters, 1856-1969
No full textTranscript of a letter by an unidentified author to David Fentress regarding sharing federal newspapers and the banning of federal newspapers in some areas. The author passes on the news of the war including the destruction of the Federal merchantmen by the Confederate fleet. He passes along world news: Russia preparing to go to War with Europe and how that could negatively affect the Confederacy. There is also speculation on the future of the war
Review of Megaprojects and Risk: An Anatomy of Ambition by Bent Flyvbjerg, Nils Bruzelius and Werner Rothengatter and Mega-projects: The Challenging Politics of Urban Public Investment by Alan Altshuler and David Luberoff .
No full textBook Review:
Megaprojects and Risk: An Anatomy of Ambition by Bent Flyvbjerg, Nils Bruzelius and Werner Rothengatter
Mega-projects: The Challenging Politics of Urban Public Investment by Alan Altshuler and David Luberoff
Two recent books on the development and deployment of large projects have recently been released. Both books tackle Megaprojects, but from somewhat different points- of-view, one European, the other American; one disparaging, the other positive; one largely statistical-empirical, the other political-historical. We consider these books in turn.Chen, Wenling; Levinson, David M. (2004). Review of Megaprojects and Risk: An Anatomy of Ambition by Bent Flyvbjerg, Nils Bruzelius and Werner Rothengatter and Mega-projects: The Challenging Politics of Urban Public Investment by Alan Altshuler and David Luberoff .. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/180159
Portrait of author David Foster at the National Library of Australia, Canberra, 8 June 2011 /
No full textTitle from acquisitions documentation.; Part of the collection: Portraits of author David Foster at the National Library of Australia, Canberra, 8 June 2011.; Acquired in digital format; access copy available online.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
No full textExome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5–5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10[superscript −8]) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10[superscript −117]). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10[superscript −4]), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.National Institutes of Health (U.S.) (NIH RC2 HL-102925
Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes
No full textPeroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF < 0.5%). Considered in aggregate (with or without computational prediction of functional consequence), these rare variants showed no association with T2D (OR = 1.35; P = 0.17). The function of the 49 variants was experimentally tested in a novel high-throughput human adipocyte differentiation assay, and nine were found to have reduced activity in the assay. Carrying any of these nine LOF variants was associated with a substantial increase in risk of T2D (OR = 7.22; P = 0.005). The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D
Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus
No full textGenome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.National Institutes of Health (U.S.) (Grant U01 DK085526)National Institutes of Health (U.S.) (Grant U01 DK085501)National Institutes of Health (U.S.) (Grant U01 DK085524)National Institutes of Health (U.S.) (Grant U01 DK085545)National Institutes of Health (U.S.) (Grant U01 DK085584)National Institutes of Health (U.S.) (Grant U01 DK088389
Author David Foster with academic Jeff Doyle at the National Library of Australia, Canberra, 8 June 2011 /
No full textTitle from acquisitions documentation.; Part of the collection: Portraits of author David Foster at the National Library of Australia, Canberra, 8 June 2011.; Acquired in digital format; access copy available online.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
Author David Foster and academic Jeff Doyle at the National Library of Australia, Canberra, 8 June 2011 /
No full textTitle from acquisitions documentation.; Part of the collection: Portraits of author David Foster at the National Library of Australia, Canberra, 8 June 2011.; Acquired in digital format; access copy available online.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
David Braithwaite at White Waltham Steam Fair
No full textDavid Braithwaite, fairground enthusiast and author photographed at White Waltham Steam Fair, August 1964
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