Poster 261 The Prevalence of Constipation as Reported by Adults With Cerebral Palsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146896/1/pmr2s261a.pd

University of Illinois Year of Cyberinfrastructure Final Report

The University of Illinois at Urbana-Champaign is a leader in computing and information technology (IT). Our leadership role has both produced and been produced by a culture of innovation. Many efforts have arisen over the years that have been the product of this culture. While the university’s commitment to developing digital infrastructure, resources, and support services has served campus researchers well, it has become clear that a more coherent and unified approach to assessing and addressing the IT services and support needs of campus researchers is imperative. With the support of the Vice Chancellor for Research and the Chief Information Officer, we embarked on the Year of Cyberinfrastructure (Year of CI). Through this effort, we engaged researchers across disciplines to gain an understanding of the challenges they face in order to inform how we, as a campus, should move together to address these needs. We confirmed that researchers tend to assemble needed resources and services on their own, often out of necessity. While this practice has allowed those with the ambition or, more frequently, the absolute need, to advance their fields, it has primarily benefitted only those researchers and their collaborators. Providers of resources and services have brought value to the research process, but this value has been accrued in a largely disjointed manner that has tended to favor the power users of technology. The Year of CI effort has made clear that our research support landscape is not only lacking coherence but is also very uneven across academic and research units. To support modern research practices and to be competitive and preeminent in the academic community and the world, the 21st century research university must provide a foundation of research IT infrastructure and services that are accessible by all disciplines. Our campus needs a strong vision for how IT supports research, along with the ability to realize and evolve that vision in lockstep with the changing needs of the research community and the technologies available to meet those needs. Though Illinois faces significant financial challenges, it is time to be bold and make an investment to allow the university to emerge from these challenges as the premier destination for faculty, postdocs, graduate students, undergraduate students, and research staff who seek to work in a world-class modern research environment. It is time to provide the infrastructure that will grow the campus research portfolio to new heights. The Year of CI has provided the initial assessment of the campus and indicates the steps we must take to develop the digital support ecosystem that will allow the campus to realize its vision of preeminence in research.Ope

Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline

ObjectiveThe study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension.Study DesignForty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected.ResultsMedian citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 μmol/L vs 26 μmol/L, P = .012) and at 12 hours postoperatively (37 μmol/L vs 20 μmol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 μmol/L vs 23 μmol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 μmol/L (P = .036).ConclusionsOral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension

Fostering Equity and Diversity in the Nova Scotia Legal Profession

The Province of Nova Scotia has, for many years, attempted, through a variety of means, to address issues of diversity and affirmative action. However, despite the lessons of history there are still those who question the need for programs and policies that promote, encourage and enforce equality. Even though significant advances have been made on many fronts Nova Scotia continues to struggle with issues of inequality. As with many problems faced by society acknowledging the existence of the problem is the first step towards developing solutions

Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: Potential therapy for postoperative pulmonary hypertension

ObjectivePulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension.MethodsThe initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 μmol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg·h) for 48 hours postoperatively.ResultsThe initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 μmol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h·kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg·h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 μmol/L, with a calculated clearance of 0.52 L/(h·kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline.ConclusionsIn this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg·h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems

MOOSE POPULATION DYNAMICS DURING 20 YEARS OF DECLINING HARVEST IN BRITISH COLUMBIA

Licenced harvest of moose (Alces alces) in British Columbia, Canada declined by approximately half over the 20-year period from 1996–2015. To better understand changes in moose populations coinciding with this period of declining harvest, we modelled population dynamics within 31 Game Management Zones (GMZs). We used aerial survey data (180 density and 159 composition surveys) combined with licensed harvest to develop 4 competing statistical models to assess population dynamics based on constant parameters and temporal trends in calf:cow ratios at 6 months, juvenile survival from 6–18 months, or cow survival. The models indicated that moose populations declined (λ < 1) in 7 GMZs (23%) from 1996–2005 and in 22 GMZs (71%) from 2006–2015. Over the 20-year period, the best model was fit with declining trends in calf:cow ratios in 8 GMZs, declining juvenile survival in 6 GMZs, and declining cow survival in 8 GMZs. Population growth rate was slightly reduced in those GMZs where licenced antlerless (cow and calf) hunting occurred but was not considered the primary factor causing population decline. Total licenced bull harvest influenced bull:cow ratios that were significantly lower in 2006–2015 (mean = 37:100) than 1995–2005 (mean = 48:100); significant predictive relationships existed between harvest rates and bull:cow ratios. Provincial moose numbers and harvest were highly correlated (r = 0.81) suggesting that declining harvest was a reaction to declining population trends. We found that the provincial moose population increased 6% from 1996–2005, subsequently declined 32% from 2006–2015, and declined 29% overall during the 20-year study period