Gaining Perspective: Lessons Learned From One Foundation's Exploratory Decade

Ten years after launching an ambitious strategy, the Northwest Area Foundation asked FSG to identify lessons learned from a decade of community-based work. In the period from 1998 to 2008, the Northwest Area Foundation made a big bet on an innovative approach to reducing poverty. Before that time, the Foundation awarded relatively short-term grants in a variety of program areas. In 1998, the mission was sharpened to a single purpose: to help communities reduce poverty. At the heart of the new strategy was a set of placebased, long-term commitments that were conceived as partnerships with entire communities.

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial

Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon- γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P \u3c .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours

Extracorporeal life support (ECLS) for pediatric trauma: experience with five cases

Extracorporeal life support (ECLS) was used to treat five pediatric trauma patients (ages 1 to 17 years) with respiratory failure unresponsive to conventional mechanical ventilation. Diagnoses in these patients that resulted in respiratory failure included hydrocarbon aspiration (one patient), multiple trauma with pulmonary contusion (two patients), bronchopleural fistula (one patient), and neardrowning (one patient). Time on ECLS bypass averaged 328 h (range 140–527 h). Physiologic complications included bleeding, cardiac arrest, cardiac tamponade, hypoxemia, and hypotension. Mechanical complications involving the bypass circuit included roller-pump raceway rupture, roller-pump failure, and membrane oxygenator failure. All complications were managed without mortality. Three of the five patients were decannulated from ECLS and survived. Support was terminated in the remaining two due to irreversibility of the pulmonary injury. ECLS may provide life-saving support to pediatric patients with respiratory failure after trauma when conventional means of ventilatory support have failed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47185/1/383_2004_Article_BF00177095.pd

Anesthesiology / second edition

xxi, 1748 pages : illustrations ; 29 c

Inhaled nitric oxide as an adjunctive treatment for cerebral malaria in children: a phase II randomized open-label clinical trial

Background.?Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods.?This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results.?Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-?, interferon-?, interleukin [IL]-1?, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P &lt; .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions.?Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours. <br/