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1.  Supplemented αMEM/F12-based medium enables the survival and growth of primary ovarian follicles encapsulated in alginate hydrogels 
Biotechnology and bioengineering  2013;110(12):10.1002/bit.24986.
Hydrogel-encapsulating culture systems for ovarian follicles support the in vitro growth of secondary follicles from various species including mouse, non-primate human, and human; however, the growth of early stage follicles (primary and primordial) has been limited. While encapsulation maintains the structure of early stage follicles, feeder cell populations, such as mouse embryonic fibroblasts (MEFs), are required to stimulate growth and development. Hence, in this report, we investigated feeder-free culture environments for early stage follicle development. Mouse ovarian follicles were encapsulated within alginate hydrogels and cultured in various growth medium formulations. Initial studies employed embryonic stem cell medium formulations as a tool to identify factors that influence the survival, growth, and meiotic competence of early stage follicles. The medium formulation that maximized survival and growth was identified as αMEM/F12 supplemented with fetuin, insulin, transferrin, selenium, and follicle stimulating hormone (FSH). This medium stimulated the growth of late primary (average initial diameter of 80 µm) and early secondary (average initial diameter of 90 µm) follicles, which developed antral cavities and increased to terminal diameters exceeding 300 µm in 14 days. Survival ranged from 18% for 80 µm follicles to 36% for 90 µm follicles. Furthermore, 80% of the oocytes from surviving follicles with an initial diameter of 90–100 µm underwent germinal vesicle breakdown (GVBD), and the percentage of metaphase II (MII) eggs was 50%. Follicle/oocyte growth and GVBD/MII rates were not significantly different from MEF co-culture. Survival was reduced relative to MEF co-culture, yet substantially increased relative to the control medium that had been previously used for secondary follicles. Continued development of culture medium could enable mechanistic studies of early stage folliculogenesis and emerging strategies for fertility preservation.
PMCID: PMC3808526  PMID: 23801027
2.  Technical Desiderata for the Integration of Genomic Data into Electronic Health Records 
Journal of Biomedical Informatics  2011;45(3):419-422.
The era of “Personalized Medicine,” guided by individual molecular variation in DNA, RNA, expressed proteins and other forms of high volume molecular data brings new requirements and challenges to the design and implementation of Electronic Health Records (EHRs). In this article we describe the characteristics of biomolecular data that differentiate it from other classes of data commonly found in EHRs, enumerate a set of technical desiderata for its management in healthcare settings, and offer a candidate technical approach to its compact and efficient representation in operational systems.
PMCID: PMC3328607  PMID: 22223081
Electronic Health Records; Genomics; Knowledge representation; Data compression
3.  Embryonic Fibroblasts Enable the Culture of Primary Ovarian Follicles Within Alginate Hydrogels 
Tissue Engineering. Part A  2012;18(11-12):1229-1238.
Hydrogel-encapsulating culture systems support the consistent growth of ovarian follicles from various species, such as mouse, non-human primate, and human; however, further innovations are required for the efficient production of quality oocytes from early-stage follicles. In this report, we investigated the coculture of mouse ovarian follicles with mouse embryonic fibroblasts (MEFs), commonly used as feeder cells to promote the undifferentiated growth of embryonic stem (ES) cells, as a means to provide the critical paracrine factors necessary for follicle survival and growth. Follicles were encapsulated within alginate hydrogels and cocultured with MEFs for 14 days. Coculture enabled the survival and growth of early secondary (average diameter of 90–100 μm) and primary (average diameter of 70–80 μm) follicles, which developed antral cavities and increased in diameter to 251–347 μm. After 14 days, follicle survival ranged from 70% for 100-μm follicles to 23% for 70-μm follicles. Without MEF coculture, all follicles degenerated within 6–10 days. Furthermore, 72%–80% of the oocytes from surviving follicles underwent germinal vesicle breakdown (GVBD), and the percentage of metaphase II (MII) eggs was 41%–69%. Medium conditioned by MEFs had similar effects on survival, growth, and meiotic competence, suggesting a unidirectional paracrine signaling mechanism. This advancement may facilitate the identification of critical factors responsible for promoting the growth of early-stage follicles and lead to novel strategies for fertility preservation.
PMCID: PMC3360509  PMID: 22296562
4.  Meeting the Governance Challenges of Next-Generation Biorepository Research 
Science translational medicine  2010;2(15):15cm3.
Advances in clinical translational research have led to an explosion of interest in infrastructure development and data sharing facilitated by biorepositories of specimens and linked health information. These efforts are qualitatively different from the single-center sample collections that preceded them and pose substantial new ethics and regulatory challenges for investigators and institutions. New research governance approaches, which can address current and anticipated challenges, promote high-quality research, and provide a robust basis for ongoing research participation, are urgently required.
PMCID: PMC3038212  PMID: 20371468
5.  People and Organizational Issues in Research Systems Implementation 
Knowledge about people and organizational issues pertinent to implementation and maintenance of clinical systems has grown steadily over the past fifteen years. Less is known about implementation of systems used for clinical and biomedical research. In conjunction with current National Institutes of Health Roadmap efforts that promote translational research, these issues should now be identified and addressed. During the 2007 American College of Medical Informatics Symposium, members discussed behavioral aspects of translational informatics. This article summarizes that discussion, which covered organizational issues, implications of how knowledge about clinical systems implementation can inform research systems implementation, and those issues unique to each kind of system.
PMCID: PMC2410012  PMID: 18308986
6.  Issues in Biomedical Research Data Management and Analysis: Needs and Barriers 
A. Identify the current state of data management needs of academic biomedical researchers. B. Explore their anticipated data management and analysis needs. C. Identify barriers to addressing those needs.
A multimodal needs analysis was conducted using a combination of an online survey and in-depth one-on-one semi-structured interviews. Subjects were recruited via an e-mail list representing a wide range of academic biomedical researchers in the Pacific Northwest.
The results from 286 survey respondents were used to provide triangulation of the qualitative analysis of data gathered from 15 semi-structured in-depth interviews.
Three major themes were identified: 1) there continues to be widespread use of basic general-purpose applications for core data management; 2) there is broad perceived need for additional support in managing and analyzing large datasets; and 3) the barriers to acquiring currently available tools are most commonly related to financial burdens on small labs and unmet expectations of institutional support.
Themes identified in this study suggest that at least some common data management needs will best be served by improving access to basic level tools such that researchers can solve their own problems. Additionally, institutions and informaticians should focus on three components: 1) facilitate and encourage the use of modern data exchange models and standards, enabling researchers to leverage a common layer of interoperability and analysis; 2) improve the ability of researchers to maintain provenance of data and models as they evolve over time though tools and the leveraging of standards; and 3) develop and support information management service cores that could assist in these previous components while providing researchers with unique data analysis and information design support within a spectrum of informatics capabilities.
PMCID: PMC2244904  PMID: 17460139
7.  On the persistence of supplementary resources in biomedical publications 
BMC Bioinformatics  2006;7:260.
Providing for long-term and consistent public access to scientific data is a growing concern in biomedical research. One aspect of this problem can be demonstrated by evaluating the persistence of supplementary data associated with published biomedical papers.
We manually evaluated 655 supplementary data links extracted from PubMed abstracts published 1998–2005 (Method 1) as well as a further focused subset of 162 full-text manuscripts published within three representative high-impact biomedical journals between September and December 2004 (Method 2).
For Method 1 we found that since 2001, only 71 – 92% of supplementary data were still accessible via the links provided, with 93% of these inaccessible links occurring where supplementary data was not stored with the publishing journal. Of the manuscripts evaluated in Method 2, we found that only 83% of these links were available approximately a year after publication, with 55% of these inaccessible links were at locations outside the journal of publication.
We conclude that if supplemental data is required to support the publication, journals policies must take-on the responsibility to accept and store such data or require that it be maintained with a credible independent institution or under the terms of a strategic data storage plan specified by the authors. We further recommend that publishers provide automated systems to ensure that supplementary links remain persistent, and that granting bodies such as the NIH develop policies and funding mechanisms to maintain long-term persistent access to these data.
PMCID: PMC1481620  PMID: 16712726

Results 1-7 (7)