Making Connections - Envisioning Springfield\u27s North End

This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio: 1. Input and interaction – Visioning workshops connect campus and community 2. Community-building art - Expression of place and people 3. Healthy living - Urban agriculture and education 4. Urban greenways – Abandoned railways and urban rivers and streams 5. Green infrastructure - Green streets as networks and structural framework 6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood

Extratropical transition of tropical cyclones in a multiresolution ensemble of atmosphere-only and fully coupled global climate models

Tropical cyclones undergo extratropical transition (ET) in every ocean basin. Projected changes in ET frequency under climate change are uncertain and differ between basins, so multimodel studies are required to establish confidence. We used a feature-tracking algorithm to identify tropical cyclones and performed cyclone phase-space analysis to identify ET in an ensemble of atmosphere-only and fully coupled global model simulations, run at various resolutions under historical (1950–2014) and future (2015–2050) forcing. Historical simulations were evaluated against five reanalyses for 1979–2018. Considering ET globally, ensemble-mean biases in track and genesis densities are reduced in the North Atlantic and Western North Pacific when horizontal resolution is increased from ∼100 to ∼25km. At high resolution, multireanalysis-mean climatological ET frequencies across most ocean basins as well as basins’ seasonal cycles are reproduced better than in low-resolution models. Skill in simulating historical ET interannual variability in the North Atlantic and Western North Pacific is ∼0.3, which is lower than for all tropical cyclones. Models project an increase in ET frequency in the North Atlantic and a decrease in the Western North Pacific. We explain these opposing responses by secular change in ET seasonality and an increase in lower-tropospheric, pre-ET warm-core strength, both of which are largely unique to the North Atlantic. Multimodel consensus about climate-change responses is clearer for frequency metrics than for intensity metrics. These results help clarify the role of model resolution in simulating ET and help quantify uncertainty surrounding ET in a warming climate

Sex Differences and Utility of Treadmill Testing in Long‐QT Syndrome

BACKGROUND: Diagnosis of congenital long‐QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal‐to‐borderline resting QT interval. A 3‐step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3‐step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex‐specific cutoffs beyond the resting QTc. METHODS AND RESULTS: We identified 208 LQTS likely pathogenic or pathogenic KCNQ1 or KCNH2 variant carriers in the Canadian NLQTS (National Long‐QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal‐to‐borderline range. The 4‐minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4‐minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1‐minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1‐minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients. CONCLUSIONS: The 3‐step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS

Sex Differences and Utility of Treadmill Testing in Long‐QT Syndrome

Background Diagnosis of congenital long‐QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal‐to‐borderline resting QT interval. A 3‐step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3‐step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex‐specific cutoffs beyond the resting QTc. Methods and Results We identified 208 LQTS likely pathogenic or pathogenic KCNQ1 or KCNH2 variant carriers in the Canadian NLQTS (National Long‐QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal‐to‐borderline range. The 4‐minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4‐minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1‐minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1‐minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients. Conclusions The 3‐step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS

Preparation and biological evaluation of synthetic and polymer-encapsulated congeners of the antitumor agent pactamycin: Insight into functional group effects and biological activity

The synthesis and biological analysis of a number of novel congeners of the aminocyclopentitol pactamycin is described. Specific attention was paid to the preparation of derivatives at crucial synthetic branch points of the parent structure, and biological assays revealed a number of insights into the source of pactamycin’s biological activity. Additionally, the encapsulation of pactamycin and select derivatives into the PRINT(©) nanoparticle technology was investigated as a proof-of-concept, and evidence of bioactivity modulation through nanoparticle delivery is demonstrated. This work has provided heretofore unrealized access to a large number of novel compounds for further evaluation