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The Genesis 12-19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene-environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date. [ABSTRACT FROM AUTHOR]

RATIONALE: Angiogenesis is a prominent feature of remodeling in asthma. Many proangiogenic factors are up-regulated in asthma, but little is known about levels of endogenous antiangiogenic agents. Collagen IV is decreased in the airway basement membrane in asthma. It has six alpha chains, of which the noncollagenous domain-1 domains have endogenous antiangiogenic properties. OBJECTIVES: To study the expression of the noncollagenous domain-1 of the alpha3 chain of collagen IV, tumstatin, in the airways of subjects with and without asthma and to examine the potential for tumstatin to regulate angiogenesis and inflammation. METHODS: We used immunohistochemistry and dot blots to examine the expression of tumstatin in bronchial biopsies, bronchoalveolar lavage fluid, and serum. We then used an in vitro angiogenesis assay and a murine model of allergic airways disease to explore tumstatin's biological function. MEASUREMENTS AND MAIN RESULTS: The level of tumstatin is decreased 18-fold in the airways of patients with asthma but not in subjects without asthma, including those with chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis. In vitro, recombinant tumstatin inhibited primary pulmonary endothelial cell tube formation. In a mouse model of chronic allergic airways disease, tumstatin suppressed angiogenesis, airway hyperresponsiveness, inflammatory cell infiltration, and mucus secretion and decreased levels of vascular endothelial growth factor and IL-13. CONCLUSIONS: The observation that tumstatin is decreased in asthmatic airways and inhibits airway hyperresponsiveness and angiogenesis demonstrates the potential use of antiangiogenic agents such as tumstatin as a therapeutic intervention in diseases that are characterized by aberrant angiogenesis and tissue remodeling, such as asthma. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin. OBJECTIVE: To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases. DESIGN: A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725) SETTING: A tertiary endoscopy center. PATIENTS: Low-dose aspirin recipients with peptic ulcer bleeding. INTERVENTION: 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up. MEASUREMENTS: The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks. RESULTS: 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, -3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]). LIMITATIONS: The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy. CONCLUSION: Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups.Objective: To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample.Design: Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment.Setting: 91 hospital emergency departments in 16 countries.Patients: Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata.Intervention: Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days.Measurements: The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed.Results: Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively.Limitation: Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group.Conclusion: High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days.Primary Funding Source: AstraZeneca Research and Development. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate the extent to which three putative 'environmental' risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior.MethodThe sample consisted of 2647 participants, aged 12-19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively.ResultGenetic influences overlapped for externalizing behavior and each 'environmental' risk, indicating gene-environment correlation. When controlling for the gene-environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior.ConclusionThe magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene-environment correlation. [ABSTRACT FROM AUTHOR]