Small communities lack effective transit planning methods that integrate diverse forms of knowledge, foster collaboration, and envision better transit futures. To address this need, this paper presents a case study of a project conducted in Benton Harbor, Michigan. The case study demonstrates a collaborative and data-driven scenario planning process conducted for a small region, and evaluates it through a mixed-methods research design. Through the use of quantitative normative service scenarios and qualitative exploratory scenarios, the project generated financially and operationally feasible proposals that community leaders can implement in the future, and also fostered constructive dialogue among transit stakeholders. Survey data show that participants experienced high levels of learning, engaged in quality deliberation, and are generally optimistic about the potential for improved transit. The project's approach can be replicated elsewhere through the use of five essential elements: a steering committee, stakeholder analysis, a series of engagement workshops, normative and exploratory scenarios, and interaction between data and modeling. Collaborative planning with scenarios can help the transportation field address the need to foster collaboration and epistemic inclusion in a changing world.
The protective effect of cardioplegia upon neonatal myocardium during ischemia has not been clearly established. This study evaluated the effects of cardioplegia on left ventricular function in isolated working neonatal rabbit hearts (aged 1 week) subjected to 120 minutes of global ischemia at 28 degrees C. Four groups were studied: Group 1, hypothermia alone; Group 2, intermittent washout with an oxygenated noncardioplegic solution; Group 3, multidose cardioplegia; Group 4, single-dose cardioplegia. After ischemia, cardiac output was reduced to 72% +/- 5% (mean +/- standard error of the mean) of control (p less than 0.02) in Group 1 and to 56% +/- 4% in Group 2 (p less than 0.001). In contrast, there was no significant reduction from baseline cardiac output in those animals receiving cardioplegic solution (Group 3, 93% +/- 6%, and Group 4, 97% +/- 4%). Group 2 hearts demonstrated significantly worse recovery of cardiac output and stroke volume than all other groups. After ischemia, the first derivative of left ventricular pressure fell to 73% +/- 13% of control in Group 1 (p less than 0.1) and to 89% +/- 5% in Group 2 (p less than 0.05). However, the first derivative of left ventricular pressure was restored to control values in Group 3 (118% +/- 11%) and Group 4 (114% +/- 9%). When compared to baseline, creatine kinase was higher 30 minutes after reperfusion in Group 1 (40 +/- 8 versus 143 +/- 32 IU/L/gm, p less than 0.05) and in Group 2 (39 +/- 7 versus 163 +/- 33 IU/L/gm, p less than 0.05). Creatine kinase remained unchanged from baseline in Groups 3 and 4. This study demonstrates excellent preservation of left ventricular function in the neonatal rabbit heart protected with cardioplegic solution. In contrast, neither hypothermia alone nor intermittent washout with an oxygenated noncardioplegic solution was effective in preventing myocardial dysfunction. As in adults, the administration of cardioplegic solution preserves ventricular function during ischemia in neonatal hearts.
CI-1031 (ZK-807834) is a novel, synthetic factor Xa (FXa) inhibitor with a Ki of 0.11 nM against human FXa. In human plasma in vitro, CI-1031 doubled PT and aPTT at 0.23 and 0.49 microM, respectively. The in vivo antithrombotic effect of CI-1031 was evaluated in a veno-venous shunt model of thrombosis in anesthetized rabbits. After thrombus formation was verified in the first shunts, rabbits received either vehicle or CI-1031 intravenously (bolus injection of 60, 240, or 480 microg/kg followed by an infusion of 2, 8, or 16 microg/kg/min for 140 min, respectively). The second shunts were inserted after 20 min of infusion of CI-1031 or vehicle. CI-1031 dose-dependently prolonged time to occlusion (TTO) in the second shunts (35 +/- 21, 62 +/- 24, and 120 +/- 0 min for the three dose groups, respectively, vs. 10 +/- 1 min for vehicle). Thrombus mass (TM) was reduced in a dose-dependent manner by CI-1031 (42 +/- 7, 27 +/- 6, and 18 +/- 4 mg vs. 50 +/- 4 mg for vehicle). Maximal TM reduction was 70% with an IC(50) of 0.6 microg/ml. Among all the coagulation parameters tested, PT had the best correlation with plasma CI- 1031 concentration (r = 0.97). Ex vivo plasma anti-FXa activity was also well correlated with plasma concentration of CI-1031 and with PT (r = 0.96 and 0.98, respectively). These results indicate that CI-1031, which is currently undergoing clinical evaluation, is an effective antithrombotic compound with a favorable efficacy-to-bleeding ratio. In addition, CI-1031 concentration in plasma can be monitored using PT or anti-Xa assays, thereby providing reliable methods to ensure safe and accurate dose titration of CI-1031.
Background Plasma levels of endothelin-1 (ET-1) are increased in patients and animals with severe congestive heart failure (CHF). It remains unknown, however, whether ET-1 plays a direct and contributory role in the progression of CHF. Accordingly, the present project tested the hypothesis that chronic blockade of the ET A receptor would have direct and beneficial effects on left ventricular (LV) and myocyte function in a model of CHF. Methods and Results Global LV and isolated myocyte function were examined in rabbits in the following groups (12 per group): chronic rapid ventricular pacing (RVP; 400 bpm, 3 weeks), RVP and concomitant administration of the selective ET A receptor antagonist (PD 156707 24 mg/d), and sham controls. LV fractional shortening decreased after RVP (17±5 versus 42±3%) and end-diastolic dimension increased (2.36±0.44 versus 1.24±0.18 cm) compared with controls ( P <.05). With RVP plus ET A blockade, LV fractional shortening was increased (33±6%) and end-diastolic dimension decreased (2.02±0.30 cm) compared with RVP-only values ( P <.05). Plasma norepinephrine and endothelin increased twofold in the RVP group. In the RVP plus ET A blockade group, plasma endothelin increased threefold compared with RVP values. Isolated myocyte shortening velocity declined after RVP (42±13 versus 72±10 μm/s, P <.05) compared with controls but was normalized with RVP plus ET A blockade (77±16 μm/s). Myocyte inotropic response to extracellular Ca 2+ , β-receptor stimulation, and ET-1 was reduced in the RVP group and returned to control levels with RVP and concomitant ET A receptor blockade. Conclusions The results from this study suggest that chronically elevated ET-1 levels and subsequent activation of the ET A receptor play a direct and contributory role in the progression of the CHF process. Thus, specific ET A receptor blockade may provide a new and useful therapeutic modality in the setting of CHF.
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