Diffuse intrinsic pontine glioma: poised for progress

Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies

A Competency-based Approach to Faculty Development

Background—Faculty development at the Virginia Commonwealth University School of Medicine (VCU SOM) has previously focused on enhancing teaching and learning in the medical and clinical education settings. While this work is important, this narrow focus does not address all facets a faculty member’s role. To broaden their programming, the VCU SOM faculty development team adopted a competency-based approach to the development and planning of faculty development activities. Summary of work—The Senior Associate Dean for Faculty Affairs completed a research project focused on successful medical faculty who promote through the tenure process and advance in their careers. She identified the following categories for success: teaching, service, scholarship, advancing, and leadership. Each of these categories contains action-focused competencies that align with career progression addressing early, mid, and late career stages. The faculty development team adopted the identified competencies to their curriculum development and planning processes. Summary of results—The results of this adoption have been clearer goals for learners, a mapped structure for faculty development activities, and a broader range of topics offered that align with career stages. Discussion—Faculty development activities are now categorized into five (5) categories: Teach, Lead, Serve, Discover, and Advance with each category color coded for easy recognition in event marketing materials. A new logo reflecting these competency categories is now included on all Office of Faculty Affairs communications. Faculty are beginning to recognize and register for activities they need for promotion, tenure, and advancement. Conclusions—The adoption of the competencies for success from the Senior Associate Dean’s study has enriched faculty development offerings providing a recognizable structure allowing faculty to easily identify competency areas for development

The Forced van der Pol Equation II: Canards in the reduced system

This is the second in a series of papers about the dynamics of the forced van der Pol oscillator [J. Guckenheimer, K. Hoffman, and W. Weckesser, SIAM J. Appl. Dyn. Syst., 2 (2003), pp. 1–35]. The first paper described the reduced system, a two dimensional flow with jumps that reflect fast trajectory segments in this vector field with two time scales. This paper extends the reduced system to account for canards, trajectory segments that follow the unstable portion of the slow manifold in the forced van der Pol oscillator. This extension of the reduced system serves as a template for approximating the full nonwandering set of the forced van der Pol oscillator for large sets of parameter values, including parameters for which the system is chaotic. We analyze some bifurcations in the extension of the reduced system, building upon our previous work in [J. Guckenheimer, K. Hoffman, and W. Weckesser, SIAM J. Appl. Dyn. Syst., 2 (2003), pp. 1–35]. We conclude with computations of return maps and periodic orbits in the full three dimensional flow that are compared with the computations and analysis of the reduced system. These comparisons demonstrate numerically the validity of results we derive from the study of canards in the reduced system

In Brownsville, a Struggle for Revitalization Without Displacement

As many parts of Brooklyn buzz with a startling rate of economic resurgence, Brownsville seems like a neighborhood left behind. Struggling with poverty, poor health statistics, unemployment and high crime rates, and with the highest concentration of public housing in the city, it has not seen the same commercial and real estate revival as Williamsburg, Bushwick, Crown Heights and other areas of Brooklyn. “In Brownsville, which has had challenges battling negative perceptions of this community, most of the residents are lower income and investors in the past have deemed this community as not being as good as an investment as other areas,” said Pernell Brice, executive director of the Dream Big Foundation, which funds and mentors local entrepreneurs. But new development and investment on the horizon is giving Brownsville hope that it can attract new businesses and shed its reputation as one of Brooklyn’s grittiest neighborhoods. At the same time, these plans, along with last year’s rezoning of East New York — part of Mayor Bill de Blasio’s push for affordable housing — have sparked fears that commercial revitalization could bring with it the most dreaded side-effect of gentrification: displacement of longtime residents. https://www.katiedwarren.com/brownsvill

Experiences with the Streptococcus mutans in Lakota Sioux (SMILeS) Study: Risk Factors for Caries in American Indian Children 0-3 Years

Severe Early Childhood Caries (S-ECC) is a terribly aggressive and devastating disease that is all too common in lower socio-economic children, but none more so that what is encountered in American Indian Tribes. Nationwide, approximately 27% of 2-5 year olds have decay while 62% percent of American Indian/Alaska Native children in the same age group have a history of decay (IHS 2010, NHANES 1999-2002). We have conducted a study of children from birth to 36 months of age on Pine Reservation to gain a better understanding of the variables that come into play in the development of this disease, from transmission and acquisition of Streptococcus mutans genotypes from mother to child to multiple dietary and behavioral components. This article describes how we established a direct partnership with the Tribe and the many opportunities and challenges we faced in performing this 5-year field study

Gating NO Release from Nitric Oxide Synthase

We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV–vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for wt NOS and three mutants (H134S, I223V, H134S/I223V). We have confirmed that wt gsNOS has the lowest NO release rate of known NOS enzymes, whether bacterial or mammalian. We also have found that steric clashes at positions 223 and 134 hinder NO escape, as judged by enhanced rates in the single mutants. The empirical rate of NO release from the gsNOS double mutant (H134/I223V) is nearly as rapid as that of the fastest mammalian enzymes, demonstrating that both positions 223 and 134 function as gates for escape of the product diatomic molecule

What personal and environmental factors determine frequency of urban greenspace use?

For many people, urban greenspaces are the only places where they encounter the natural world. This is concerning as there is growing evidence demonstrating that human well-being is enhanced by exposure to nature. There is, therefore, a compelling argument to increase how frequently people use urban greenspaces. This may be achieved in two complementary ways by encouraging: (I) non-users to start visiting urban greenspaces; (II) existing users to visit more often. Here we examine the factors that influence frequency of greenspace visitation in the city of Sheffield, England. We demonstrate that people who visit a site least frequently state lower self-reported psychological well-being. We hypothesised that a combination of socio-demographic characteristics of the participants, and the biophysical attributes of the greenspaces that they were visiting, would be important in influencing visit frequency. However, socio-demographic characteristics (income, age, gender) were not found to be predictors. In contrast, some biophysical attributes of greenspaces were significantly related to use frequency. Frequent use was more likely when the time taken to reach a greenspace was shorter and for sites with a higher index of greenspace neglect, but were unrelated to tree cover or bird species richness. We related these results to the motivations that people provide for their visits. Infrequent users were more likely to state motivations associated with the quality of the space, while frequent users gave motivations pertaining to physical, repeated activities. This suggests that there may be no simple way to manage greenspaces to maximise their use across user cohorts as the motivations for visits are very different

The Massachusetts Family Networks Implementation Study

Family Networks is a comprehensive systems transformation initiative to redesign and integrate traditional categorical services across the Commonwealth into local systems of care for children, youth, and families served by the child welfare system. The Family Networks Implementation Study, a partnership between the Massachusetts Department of Social Services (MA/DSS) and the University of Massachusetts Medical School, is a two-year study of the process of implementing local systems of care that began in January 2007, and will continue through December 2008. Findings from the Family Networks Implementation Study will inform MA/DSS strategic planning, system refinements, and the Family Networks outcomes evaluation. Continuous quality improvement strategies, drawn from study findings, will be relevant and useful to other Massachusetts EOHHS agencies with similar service delivery systems and agendas. Project activities and products will promote the Commonwealth’s participation in the national dialogue regarding systems transformation in child welfare, mental health, and juvenile justice

Reirradiation practices for children with diffuse intrinsic pontine glioma

Background: Diffuse intrinsic pontine gliomas (DIPGs) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in most patients, the effect is temporary and median survival is less than 1 year. The use and benefit of reirradiation have been reported in progressive DIPG, yet standardized approaches are lacking. We conducted a survey to assess reirradiation practices for DIPG in North America. Methods: A 14-question REDCap survey was disseminated to 396 North American physicians who care for children with CNS tumors. Results: The response rate was 35%. Participants included radiation-oncologists (63%; 85/135) and pediatric oncologists/neuro-oncologists (37%; 50/135). Most physicians (62%) treated 1 to 5 DIPG patients per year, with 10% treating more than 10 patients per year. Reirradiation was considered a treatment option by 88% of respondents. Progressive disease and worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) surveyed considered reirradiation a minimum of 6 months following initial RT. Doses varied, with median total dose of 2400 cGy (range, 1200-6000 cGy) and fraction size of 200 cGy (range, 100-900 cGy). Concurrent use of systemic agents with reirradiation was considered in 46%, including targeted agents (37%), biologics (36%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Conclusion: Although the vast majority of physicians consider reirradiation as a treatment for DIPG, total doses and fractionation varied. Further clinical trials are needed to determine the optimal radiation dose and fractionation for reirradiation in children with progressive DIPG