VEGF immobilization and VEGFR2 trafficking and phosphorylation: in vitro and in vivo implications

Modern drug development is marked by high failure rates in translation to the clinic. Further, many drugs that succeed in clinical trials work for only a fraction of patients. Systems pharmacology attempts to address these challenges by improving our understanding of the disease-therapy system, integrating detailed molecular interactions, cellular signaling, tissue architecture, and whole body physiology. I built cutting-edge, molecularly-detailed, multi-scale computational models to study the effects of immobilization of growth factors on signaling in angiogenesis, focusing in particular on the binding of vascular endothelial growth factor (VEGF) family members to the ECM. While most studies of VEGF signaling use only VEGF presented in solution, there is evidence that a large potion of VEGF may be ECM-bound in vivo, and relative expression of isoforms binding to ECM vs. found only in solution varies by tissue and changes in disease, motivating further study of this question. Starting at the in vitro level, we showed that differential signaling of VEGF-receptor 2 (VEGFR2) in response to soluble vs. immobilized VEGF can be explained by reduced internalization of ECM-VEGF-VEGFR2 complexes. Moving in vivo, we predicted differences in both growth factor distribution and receptor activation by VEGF family ligands, as a function of their ECM-binding properties. These predictions are consistent with observed vascular phenotypes in mice expressing single VEGF isoforms. Next, we explored how VEGF splicing changes in peripheral artery disease lead to impaired angiogenic responses to ischemia. Our model showed that the VEGF165b isoform, which does not bind to ECM or to the coreceptor NRP1, is a weak activator of VEGFR2 in vivo, and competes for binding to VEGF-receptor 1, but not VEGF-receptor 2. Finally, we used this model to screen potential therapeutic strategies designed to promote VEGF-mediated revascularization in ischemic disease and tissue engineering applications. Within a single system, we compared failed and promising biomaterial-based VEGF delivery systems, antibody-based therapeutics, and gene therapy strategies to identify key rules for design, optimization, and translation of these pro-angiogenic therapies

The Iowa Homemaker vol.21, no.3

Freshmen – Please Note, page 2 Hospital Research, Ann Koebel, page 3 Orchids to Pat, page 4 The Army Eats Well, Mary I. Barber, page 5 Making Things Grow, Betty Ann Iverson, page 6 Look Before You Snap, Kathryn Monson, page 7 Major Departments on Review, Elizabeth Murfield, page 8 Patriotic Sally, Patricia Hayes, page 10 What’s New in Home Economics, Dorothy Olson, page 12 Summer Job Holders Reap Experience, page 14 A List of Don’ts, Costume Design Class, page 15 We Salute Campus Leaders, Margaret Kirchner, page 16 Home Economics Looks to Future, M. L. Morton, page 17 Behind Bright Jackets, Julie Wendel, page 18 Alums in the News, Mary Elizabeth Sather, page 20 Nutrition for Defense, Dorothy Ann Roost, page 22 That Personal Touch, Margaret Ann Clarke, page 23 Journalistic Spindles, Elizabeth Hanson, page 2

The Iowa Homemaker vol.21, no.2

Rejuvenation, Editor, page 1 The Union Way, Dorothy Ann Klein, page 2 Spices Feel War’s Sting, Clara Collar, page 4 The Institution Management Department, Margaret Read, page 5 Food for 5000, Margaret Mitchell, page 6 Sally’s Ready for Play, Dorothy Roost, page 8 Food Work Proves Intriguing, Ruth Kunerth, page 10 What’s New in Home Economics, page 12 Speaking of Veishea, Virginia Daley, page 14 Novelties in Dining Out, Elizabeth Murfield, page 15 Aluminum Is Drafted, Stuart Swensson, page 16 Alums in the News, Mary Sather, page 19 Campers Must Eat, Doris Plagge, page 20 Behind Bright Jackets, Julie Wendel, page 21 Journalistic Spindles, Mary Schmidt, page 2

Torsion of the Gallbladder

A 77-year-old woman was seen with progressive abdominal pain. A CT scan was made and showed a large gallbladder extending into the right lower abdomen. Ultrasound was performed but demonstrated no gallstones. Laparoscopy showed a tordated, necrotic gallbladder that was attached to the liver only by the cystic artery and cystic duct. Cholecystectomy was performed. Torsion of the gallbladder is a rare but clinically important condition in which the diagnosis seldom is made preoperatively. In radiological and clinical signs of cholecystitis without gallstones, this condition should be considered

The Iowa Homemaker vol.22, no.1

Keeping Up With Today, page 2 Meat – to the Front, Dorothy Ann Roost, page 3 When Defense Workers Eat, Marjorie Beneke, page 4 “Martha Duncan Says to You”, Julie Wendel, page 5 Design for Spring, Trymby Calhoun, page 6 Homemaking on the Test, Katherine Kaufman, page 8 A Textiles Journalist Talks Shop, Ida Halpin, page 9 What’s New in Home Economics, Ruth Vogel, page 10 Dress for Action, Betty Roth, page 12 Army Health Marches On, Marabeth Porter, page 13 Departmental Highlights, Lila Williamson, page 14 Across Alumnae Desks, Mary Ellen Sullivan, page 15 A Book for Home Managers, Helen Pundt, page 16 Alums in the News, Harriet Zook, page 18 Bookmarks, Eileen Dudgeon, page 19 Victory Shipments Advance, Bernadine Nelson, page 2

MIxS-BE : a MIxS extension defining a minimum information standard for sequence data from the built environment

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 8 (2014): 1-3, doi:10.1038/ismej.2013.176.The need for metadata standards for microbe sampling in the built environment.We would like to thank the Alfred P Sloan Foundation grant FP047325-01-PR for support for this project

The Iowa Homemaker vol.21, no.8

We Want to Be Likeable, Mary Ellen Sullivan, page 2 Cotton hose Enlist Glamour, Elizabeth Ann Murfield, page 3 Memorial Union Plans Food for a Year, Pat Garberson, page 4 Government Drafts Textiles, Patricia Hayes, page 5 Gay Clothes Boost Sally’s Morale, Virginia Brainard, page 7 War Revamps Textile World, Betty Roth, page 8 Dehydrated Foods Gain New Victories, Janet Wilson, page 9 What’s New in Home Economics, Dorothy Olson, page 10 Departmental Highlights, Lila Williamson, page 12 War Rations British Homemaking, Marabeth Paddock, page 13 Across Alumnae Desks, Marjorie Thomas, page 14 Bookmarks, Julie Wendel, page 15 File That Information, Barbara Burbank, page 17 Alums in the News, Bette Simpson, page 18 For Victory, Margaret Ann Kirchner, page 20 Spindles, Trymby Calhoun, page 2

Measuring adherence to antiretroviral therapy in northern Tanzania: feasibility and acceptability of the Medication Event Monitoring System

Peer reviewedPublisher PD

Does Consideration and Assessment of Effects on Health Equity Affect the Conclusions of Systematic Reviews? A Methodology Study

INTRODUCTION: Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. METHODS: We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. RESULTS: Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. CONCLUSION: The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews

What makes health impact assessments successful? Factors contributing to effectiveness in Australia and New Zealand

Background: While many guidelines explain how to conduct Health Impact Assessments (HIAs), less is known about the factors that determine the extent to which HIAs affect health considerations in the decision making process. We investigated which factors are associated with increased or reduced effectiveness of HIAs in changing decisions and in the implementation of policies, programs or projects. This study builds on and tests the Harris and Harris-Roxas' conceptual framework for evaluating HIA effectiveness, which emphasises context, process and output as key domains. Methods: We reviewed 55 HIA reports in Australia and New Zealand from 2005 to 2009 and conducted surveys and interviews for 48 of these HIAs. Eleven detailed case studies were undertaken using document review and stakeholder interviews. Case study participants were selected through purposeful and snowball sampling. The data were analysed by thematic content analysis. Findings were synthesised and mapped against the conceptual framework. A stakeholder forum was utilised to test face validity and practical adequacy of the findings. Results: We found that some features of HIA are essential, such as the stepwise but flexible process, and evidence based approach. Non-essential features that can enhance the impact of HIAs include capacity and experience; 'right person right level'; involvement of decision-makers and communities; and relationships and partnerships. There are contextual factors outside of HIA such as fit with planning and decision making context, broader global context and unanticipated events, and shared values and goals that may influence a HIA. Crosscutting factors include proactive positioning, and time and timeliness. These all operate within complex open systems, involving multiple decision-makers, levels of decision-making, and points of influence. The Harris and Harris-Roxas framework was generally supported. Conclusion: We have confirmed previously identified factors influencing effectiveness of HIA and identified new factors such as proactive positioning. Our findings challenge some presumptions about 'right' timing for HIA and the rationality and linearity of decision-making processes. The influence of right timing on decision making needs to be seen within the context of other factors such as proactive positioning. This research can help HIA practitioners and researchers understand and identify what can be enhanced within the HIA process. Practitioners can adapt the flexible HIA process to accommodate the external contextual factors identified in this report