Spring 1970

Response of Coastal Bermudagrass to Nitrogen by D.A. Mays and G. L. Terman (page 3) Soil & Water Resources by Fred P. Miller (7) Organization Against Oil by R. B. Clark (9) 1970 Turf Conference Program (12) Principles for Any Green by Wayne Morgan (16) An Effective Technique for Recognition by Howard Gaskill (18) Ten Years of Decisions by James W. Brandt (21

A quantified triple bottom line for tourism: experimental results

The tradition of tourism businesses and regional tourism industries is to measure their value to the host community by jobs, wages and tax revenues even though every member of that community is impacted on a daily basis though a broad variety of impacts. This paper demonstrates a conceptual approach for measuring the relative importance of the major dimensions of community quality of life that can be influenced by the tourism industry in order to calculate an indication of overall impact on the well being of community residents. Furthermore, we have formulated a conjoint model that values this overall performance in monetary units. A conjoint model for estimating importance is successfully implemented using samples of college students and tourism industry professionals in the US and Cyprus. A monetary version of Triple Bottom Line impacts is calculated for the impacts of a specific hypothetical tourism business development

Probenecid improves cardiac function in subjects with a fontan circulation and augments cardiomyocyte calcium homeostasis

Subjects with functionally univentricular circulation who have completed staged single ventricle palliation, with the final stage culminating in the Fontan procedure, are often living into adulthood. However, high morbidity and mortality remain prevalent in these patients, as diastolic and systolic dysfunction of the single systemic ventricle are linked to Fontan circulatory failure. We presently investigated the effects of probenecid in post-Fontan patients. Used for decades for the treatment of gout, probenecid has been shown in recent years to positively influence cardiac function via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in cardiomyocytes. Indeed, we observed that probenecid improved cardiac function and exercise performance in patients with a functionally univentricular circulation. This was consistent with our findings from a retrospective cohort of patients with single ventricle physiology where TRPV2 expression was increased. Experiments in isolated cardiomyocytes associated these positive actions to augmentation of diastolic calcium homeostasis

Abstract 177: Exploratory Results From the B01-02 Trial: Administration of MultiStem® Results in Decreased Circulating CD3+ Cells and Lower Levels of Inflammatory Cytokines

Introduction: B01-02 was a double-blind, placebo-controlled study of ischemic stroke patients (NIHSS 8-20, inclusive) treated within 24-48 hours of symptom onset with MultiStem, an adult, adherent, stem cell product. In pre-clinical models of stroke, MultiStem appears to confer improved neurological benefit through multiple mechanisms, including down-regulation of the peripheral immune response. We sought to determine whether this observation translated to acute ischemic stroke patients treated with MultiStem. Methods: Patients were randomized 1:1 and received IV infusion of 1.2 billion cells or placebo. After randomization, patients had blood drawn to determine baseline levels of circulating levels of CD3+ cells or specific inflammatory cytokines. Blood was drawn again at days 2, 7 and 30 post-treatment to determine the average fold change from baseline in each patient at each time point. Results: 126 patients formed the Intention-To-Treat (ITT) population, 65 receiving MultiStem, 61 placebo. 38 MultiStem patients and 40 placebo patient samples were analyzed for CD3+ cells, while 60 MultiStem patients and 55 placebo patients samples were analyzed for serum cytokine levels. CD3+ cell levels were significantly decreased in the MultiStem treatment group compared to placebo (p=0.001) at Day 2, but not later. IL-6 (p=.031) and IL-12 (p=.035) were both significantly downregulated in the MultiStem treatment group at Day 7. IL-1β (p=.065), TNF-α (p=.068) and IFN-γ (p=.100) also trended towards being significantly reduced at Day 7. Conclusions: IV administration of MultiStem within 24-48 hours of an ischemic stroke results in decreased circulating CD3+ cells, while reducing inflammatory cytokines in the blood during the first 7 days after onset of symptoms. These results support the hypothesis that MultiStem treatment limits the activation of the innate immune system’s response to stroke, which may provide improved neurological and recovery outcomes. Additional studies are required to confirm this observation and optimize the time of administration for MultiStem mediated benefi

Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18-83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8-20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24-48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55-2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc

Isosorbide dinitrate effect on hemodynamic profile, liver stiffness, and exercise tolerance in Fontan circulation (the NEET clinical trial)

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2–39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT04297241

Estimating Populations of Men Who Have Sex with Men in the Southern United States

Population estimates of men who have sex with men (MSM) by state and race/ethnicity are lacking, hampering effective HIV epidemic monitoring and targeting of outreach and prevention efforts. We created three models to estimate the proportion and number of adult males who are MSM in 17 southern states. Model A used state-specific census data stratified by rural/suburban/urban area and national estimates of the percentage MSM in corresponding areas. Model B used a national estimate of the percentage MSM and state-specific household census data. Model C partitioned the statewide estimates by race/ethnicity. Statewide Models A and B estimates of the percentages MSM were strongly correlated (r = 0.74; r-squared = 0.55; p < 0.001) and had similar means (5.82% and 5.88%, respectively) and medians (5.5% and 5.2%, respectively). The estimated percentage MSM in the South was 6.0% (range 3.6–13.2%; median, 5.4%). The combined estimated number of MSM was 2.4 million, including 1,656,500 (69%) whites, 339,400 (14%) blacks, 368,800 (15%) Hispanics, 34,600 (1.4%) Asian/Pacific Islanders, 7,700 (0.3%) American Indians/Alaska Natives, and 11,000 (0.5%) others. The estimates showed considerable variability in state-specific racial/ethnic percentages MSM. MSM population estimates enable better assessment of community vulnerability, HIV/AIDS surveillance, and allocation of resources. Data availability and computational ease of our models suggest other states could similarly estimate their MSM populations