A 'Teague' and a 'True Briton': Charles Johnstone, Ireland, and Empire

Charles Johnstone's literary output - which included Chrysal: or, the Adventures of a Guinea (1760) and a series of novels between 1762 and 1781 prior to his departure for Calcutta in 1782 - features a marked geographical and historical preoccupation with empire. The trajectory of Johnstone's life from Carrigogunnell and Dublin in Ireland, to London, and finally to Calcutta, indicates the remarkable possibilities for self-transformation which empire from Ireland to India offered during the eighteenth century. This paper examines the significance of empire in Johnstone's oeuvre, and identifies for the first time a series of articles written by him in The Calcutta Gazette in 1785.

Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond e2 and e4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Late Holocene sea-level fall and turn-off of reef flat carbonate production: Rethinking bucket fill and coral reef growth models

Relative sea-level rise has been a major factor driving the evolution of reef systems during the Holocene. Most models of reef evolution suggest that reefs preferentially grow vertically during rising sea level then laterally from windward to leeward, once the reef flat reaches sea level. Continuous lagoonal sedimentation ("bucket fill") and sand apron progradation eventually lead to reef systems with totally filled lagoons. Lagoonal infilling of One Tree Reef (southern Great Barrier Reef) through sand apron accretion was examined in the context of late Holocene relative sea-level change. This analysis was conducted using sedimentological and digital terrain data supported by 50 radiocarbon ages from fossil microatolls, buried patch reefs, foraminifera and shells in sediment cores, and recalibrated previously published radiocarbon ages. This data set challenges the conceptual model of geologically continuous sediment infill during the Holocene through sand apron accretion. Rapid sand apron accretion occurred between 6000 and 3000 calibrated yr before present B.P. (cal. yr B.P.); followed by only small amounts of sedimentation between 3000 cal. yr B.P. and present, with no significant sand apron accretion in the past 2 k.y. This hiatus in sediment infill coincides with a sea-level fall of similar to 1-1.3 m during the late Holocene (ca. 2000 cal. yr B.P.), which would have caused the turn-off of highly productive live coral growth on the reef flats currently dominated by less productive rubble and algal flats, resulting in a reduced sediment input to back-reef environments and the cessation in sand apron accretion. Given that relative sea-level variations of similar to 1 m were common throughout the Holocene, we suggest that this mode of sand apron development and carbonate production is applicable to most reef systems.