From Angela's Ashes to the Celtic Tiger: Early Life Conditions and Adult Health in Ireland

We use data from the Irish census and exploit regional and temporal variation in infant mortality rates over the 20th century to examine effects of early life conditions on later life health. Our main identification is public health interventions which eliminated the Irish urban infant mortality penalty. Estimates suggest that a unit decrease in mortality rates at time of birth reduces the probability of being disabled as an adult by between .03 and .05 percentage points. We find that individuals from lower socio economic groups had marginal effects of reduced infant mortality twice as large as those at the top.childhood health, disability

Discovery of a Very Young Field L Dwarf, 2MASS J01415823-4633574

While following up L dwarf candidates selected photometrically from the Two Micron All Sky Survey, we uncovered an unusual object designated 2MASS J01415823-4633574. Its optical spectrum exhibits very strong bands of vanadium oxide but abnormally weak absorptions by titanium oxide, potassium, and sodium. Morphologically such spectroscopic characteristics fall intermediate between old, field early-L dwarfs (log(g)~5) and very late M giants (log(g)~0), leading us to favor low gravity as the explanation for the unique spectral signatures of this L dwarf. Such a low gravity can be explained only if this L dwarf is much lower in mass than a typical old field L dwarf of similar temperature and is still contracting to its final radius. These conditions imply a very young age. Further evidence of youth is found in the near-infrared spectrum, including a triangular-shaped H-band continuum reminiscent of young brown dwarf candidates discovered in the Orion Nebula Cluster. Using the above information along with comparisons to brown dwarf atmospheric and interior models, our current best estimate is that this L dwarf has an age of 1-50 Myr and a mass of 6-25 M_Jupiter. The location of 2MASS 0141-4633 on the sky coupled with a distance estimate of ~35 pc and the above age estimate suggests that this object may be a brown dwarf member of either the 30-Myr-old Tucana/Horologium Association or the ~12-Myr-old beta Pic Moving Group.Comment: Accepted for publication in the 10 March 2006 issue (volume 639) of the Astrophysical Journa

Denial at the top table: status attributions and implications for marketing

Senior marketing management is seldom represented on the Board of Directors nowadays, reflecting a deteriorating status of the marketing profession. We examine some of the key reasons for marketing’s demise, and discuss how the status of marketing may be restored by demonstrating the value of marketing to the business community. We attribute marketing’s demise to several related key factors: narrow typecasting, marginalisation and limited involvement in product development, questionable marketing curricula, insensitivity toward environmental change, questionable professional standards and roles, and marketing’s apparent lack of accountability to CEOs. Each of these leads to failure to communicate, create, or deliver value within marketing. We argue that a continued inability to deal with marketing’s crisis of representation will further erode the status of the discipline both academically and professionally

Characterization of candidate genes in inflammatory bowel disease-associated risk loci

GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn\u27s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis

First isolation of Brucella pinnipedialis and detection of Brucella antibodies from bearded seals Erignathus barbartus

Brucella species infecting marine mammals was first reported in 1994 and in the years since has been documented in various species of pinnipeds and cetaceans. While these reports have included species that inhabit Arctic waters, the few available studies on bearded seals Erignathus barbatus have failed to detect Brucella infection to date. We report the first isolation of Brucella pinnipedialis from a bearded seal. The isolate was recovered from the mesenteric lymph node of a bearded seal that stranded in Scotland and typed as ST24, a sequence type associated typically with pinnipeds. Furthermore, serological studies of free-ranging bearded seals in their native waters detected antibodies to Brucella in seals from the Chukchi Sea (1990-2011; 19%) and Svalbard (1995-2007; 8%), whereas no antibodies were detected in bearded seals from the Bering Sea or Bering Strait or from captive bearded seals

Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses

Intestinal macrophages are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters intestinal macrophage programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient mice. In both bone-marrow-derived and intestinal macrophages, we identified chromatin accessibility changes associated with bacterial exposure and IL-10-deficiency. Surprisingly, IL-10-deficient intestinal macrophages adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, if IL-10 protein was added to cells that had previously been IL-10-deficient, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model where IL-10-deficiency leads to chromatin alterations that contribute to a loss of intestinal macrophage tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation

Molecular classification of Crohn's disease reveals two clinically relevant subtypes

The clinical presentation and course of Crohn’s disease (CD) is highly variable. We sought to better understand the cellular and molecular mechanisms that guide this heterogeneity, and characterize the cellular processes associated with disease phenotypes

Exosome-Producing Follicle Associated Epithelium Is Not Involved in Uptake of PrPd from the Gut of Sheep (Ovis aries): An Ultrastructural Study

In natural or experimental oral scrapie infection of sheep, disease associated prion protein (PrPd) often first accumulates in Peyer's patch (PP) follicles. The route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. In a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated PrPd was detected by light microscopy shortly (15 minutes to 3.5 hours) after inoculation in the villous lacteals and sub-mucosal lymphatics. No PrPd was located within the follicle-associated epithelium (FAE), sub-FAE domes or the PP follicles. To evaluate this gut loop model and the transportation routes in more detail, we used electron microscopy (EM) to study intestinal tissues exposed to scrapie or control homogenates for 15 minutes to 10 days. In addition, immuno-EM was used to investigate whether exosomes produced in the FAE may possess small amounts of PrPd that were not detectable by light microscopy. This study showed that the integrity of the intestinal epithelium was sustained in the intestinal loop model. Despite prominent transcytotic activity and exosome release from the FAE of the ileal PP in sheep, these structures were not associated with transportation of PrPd across the mucosa. The study did not determine how infectivity reaches the follicles of PPs. The possibility that the infectious agent is transported across the FAE remains a possibility if it occurs in a form that is undetectable by the methods used in this study. Infectivity may also be transported via lymph to the blood and further to all other lymphoid tissues including the PP follicles, but the early presence of PrPd in the PP follicles during scrapie infection argues against such a mechanism