‘”Like an Old Cathedral City”: Belfast Welcomes Queen Victoria, August 1849’,

Belfast, with its history of communal violence, is normally seen as lying outside the mainstream of nineteenth-century British urban development. The visit of Queen Victoria in 1849 suggests a more complex, less linear picture. What emerges is an urban identity in transition, in which aspirations to conform to an ideal of civic harmony temporarily overrode acute sectarian and political divisions, where pride in recent economic achievement sat uneasily alongside an awareness of the town’s newcomer status, and where an emerging sense of regional difference competed with a continuing assumption of Irish identity.

Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

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.

Introduction Special Section on David Clarke's Archaeology: the Loss of Innocence 25 years after:with Simon Stoddart

Malone, C.A.T. and S.K.F. Stoddart, Special Section. Introduction. David Clarke's 'Archaeology: the loss of Innocence' (1973) 25 years after.

The Beta Agonist Lung Injury Trial Prevention:A Randomized Controlled Trial

Rationale: Experimental studies suggest that pretreatment with b-agonists might prevent acute lung injury (ALI).

Objectives: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled b-agonists effects the development of early ALI.

Methods:We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 mg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury.

Measurements and Main Results: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life.Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury.

Conclusion: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI.

Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).Copyright © 2014 by the American Thoracic Society.

Infrastructure and the Architectures of Modernity in Ireland 1916-2016

At the formation of the new Republic of Ireland, the construction of new infrastructures was seen as an essential element in the building of the new nation, just as the adoption of international style modernism in architecture was perceived as a way to escape the colonial past. Accordingly, infrastructure became the physical manifestation, the concrete identity of these objectives and architecture formed an integral part of this narrative. Moving between scales and from artefact to context, Infrastructure and the Architectures of Modernity in Ireland 1916-2016 provides critical insights and narratives on what is a complex and hitherto overlooked landscape, one which is often as much international as it is Irish. In doing so, it explores the interaction between the universalising and globalising tendencies of modernisation on one hand and the textures of local architectures on the other.

The book shows how the nature of technology and infrastructure is inherently cosmopolitan. Beginning with the building of the heroic Shannon hydro-electric facility at Ardnacrusha by the German firm of Siemens-Schuckert in the first decade of independence, Ireland became a point of varying types of intersection between imported international expertise and local need. Meanwhile, at the other end of the century, by the year 2000, Ireland had become one of the most globalized countries in the world, site of the European headquarters of multinationals such as Google and Microsoft. Climatically and economically expedient to the storing and harvesting of data, Ireland has subsequently become a repository of digital information farmed in large, single-storey sheds absorbed into anonymous suburbs. In 2013, it became the preferred site for Intel to design and develop its new microprocessor chip: the Galileo. The story of the decades in between, of shifts made manifest in architecture and infrastructure from the policies of economic protectionism, to the opening up of the country to direct foreign investment and the embracing of the EU, is one of the influx of technologies and cultural references into a small country on the edges of Europe as Ireland became both a launch-pad and testing ground for a series of aspects of designed modernity.