University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis

Abstract: We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.

Calcium plus vitamin D supplementation and the risk of fractures.

Abstract: Background The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. Methods We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Results Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with...

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.

Abstract: Importance Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using theI2statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. Exposures Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82];P Conclusions and Relevance In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

The development of spatial representations of large-scale environments

Abstract: Publisher Summary A series of neurological and philosophical discussions has led to suggestions that space is a model of the environment, constructed from the temporal integration of successive perceptions, which model man as neurologically disposed to create and organize. The model is coordinated to social conventions. It develops and is vulnerable to dissolution. Studies of adults' knowledge about their macroenvironment suggest that human “maps” are not literally maps. Rather, they tend to be fragmented, distorted projectively, and are often several multiple “mini-spatial-representations.” Landmarks and routes are the minimal elements of spatial representation. Survey-representations incorporate configurational elements (outlines, graphic skeletons, figurative metaphors) and may be the final derivative of dense, richly interconnected, and hierarchically organized route maps. The notion of “main sequences” was introduced as a potential explanation for the extensive parallelisms identified among ontogenesis, microgenesis, the course of pathology, and the recovery of function following pathological insult. The development of the sequence of spatial representations in children conforms to the “main sequence” identified in the construction of spatial representation in adults.

Who Matters to Ceos? An Investigation of Stakeholder Attributes and Salience, Corpate Performance, and Ceo Values

Abstract: Using unique data provided by the CEOs of 80 large U.S. firms, the authors examined relationships among the stakeholder attributes of power, legitimacy, urgency, and salience; CEO values; and corpo...