Boston University

About: Boston University is a education organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 48688 authors who have published 119622 publications receiving 6276020 citations. The organization is also known as: BU & Boston U.

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Targeted Anticytokine Therapy in Patients with Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)

Abstract: Background— Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Methods and Results— Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction ≤0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE ( P =0.17) or RECOVER ( P =0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P =0.33). Conclusions— The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.

Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.

Abstract: Context Little randomized evidence is available to guide the in-hospital management of patients with an acute exacerbation of chronic heart failure. Although intravenous inotropic therapy usually produces beneficial hemodynamic effects and is labeled for use in the care of such patients, the effect of such therapy on intermediate-term clinical outcomes is uncertain. Objective To prospectively test whether a strategy that includes short-term use of milrinone in addition to standard therapy can improve clinical outcomes of patients hospitalized with an exacerbation of chronic heart failure. Design Prospective, randomized, double-blind, placebo-controlled trial conducted from July 1997 through November 1999. Setting Seventy-eight community and tertiary care hospitals in the United States. Participants A total of 951 patients admitted with an exacerbation of systolic heart failure not requiring intravenous inotropic support (mean age, 65 years; 92% with baseline New York Heart Association class III or IV; mean left ventricular ejection fraction, 23%). Intervention Patients were randomly assigned to receive a 48-hour infusion of either milrinone, 0.5 microg/kg per minute initially (n = 477), or saline placebo (n = 472). Main outcome measure Cumulative days of hospitalization for cardiovascular cause within 60 days following randomization. Results The median number of days hospitalized for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) compared with placebo (7 days; P =.71). Sustained hypotension requiring intervention (10.7% vs 3.2%; P Conclusion These results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in the treatment of patients hospitalized for an exacerbation of chronic heart failure.

Projections to the frontal cortex from the posterior parietal region in the rhesus monkey.

Abstract: The projections to the frontal cortex from the various subdivisions of the posterior parietal region in the rhesus monkey were studied by means of autoradiographic technique. The rostral superior parietal lobule (area PE) projects to the dorsal areas 4 and 6 on the lateral surface of the frontal lobe as well as to the supplementary motor area (MII) on its medial surface. The caudal area PE sends its connections to dorsal area 6 and MII. The projections from the medial parietal cortex (areas PEc and PGm) are similar to those of the superior parietal lobule but they tend to concentrate in the more rostral part of dorsal area 6, MII, and in the cingulate gyrus (area 24). The most caudal part of the medial parietal cortex also projects to area 8. The anteriormost part of the inferior parietal lobule (area PF) projects to the ventral area 6, including the caudal bank of the lower branch of the arcuate sulcus, to the ventral area 46 below the sulcus principalis, and to the frontal and pericentral opercular cortex. The middle inferior parietal lobule (areas PFG and PG) projects to the ventral part of area 46 and area 8, whilst the posteriormost inferior parietal lobule (caudal PG and area Opt) is connected with both dorsal and ventral area 46, dorsal area 8, as well as the anteriormost dorsal area 6, and the cingulate gyrus (area 24).